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The Interrelationship between Liver Function Test and the Coronavirus Disease 2019: A Systematic Review and Meta-Analvsis.

Introduction

Globally, in February 2021, the cumulative number of coronavirus disease-2019 (COVID-19) infections had reached over 102.1 million reported cases. (1) The incidence and mortality rates are still increasing, especially among older adults and patients with comorbidity. Clinical manifestation of COVID-19 varies from asymptomatic or mild symptomatic symptoms to cough, fever, fatigue, gastrointestinal symptoms; shortness of breath and dyspnea, acute respiratory distress, shock, and even the risk of death. (2-6) Infected patients may suffer from liver dysfunction characterized by abnormal liver tests, particularly in severe cases. (7-11) Therefore, it is extremely important to assess the effect of COVID-19 infection on liver function. (11-13) A recent study on the alteration in liver enzyme levels due to COVID-19 infection has indicated that higher levels of aspartate aminotransferase (AST) and direct bilirubin increase the risk of requiring critical care or admission to an intensive care unit (ICU). Elevated AST, alanine aminotransferase (ALT), total bilirubin (TBIL) levels, and low albumin levels have been reported in severe cases. (14,) (15) It is reported that an AST level of 30.5 (U/L) has a sensitivity of 71.4% and specificity of 68.5% for ICU transfer. (16)

Previous studies of patients with liver damage reported increased levels of other biomarkers such as D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactate dehydrogenase (LDH) in addition to abnormal liver enzymes. (17,) (18) This necessitates an additional focus on the assessment of biomarkers related to liver function in COVID-19 patients with varying degrees of liver damage.

Recent studies on liver damage due to the COVID-19 outbreak have not been comprehensive and lack a comparison between the extent of the damage and the severity of the disease. In the present study, we reviewed both research data and experts' opinions on the correlation between COVID-19 and liver injury. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID 19 patients.

Materials and Methods

Search Strategy

The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). (19) Our systematic search included publications in Web of Science, Scopus, and Medline (via PubMed) databases from December 2019 up to April 2020. Both cross-sectional and case series studies, even those in preprint state, were included. Important references and related reviews of these articles were examined using the Google Scholar web search engine. The search was performed independently by two researchers using medical keywords "2019 novel coronavirus infection" OR "COVID19 OR COVID-19" OR "Coronavirus disease 2019" OR "Coronavirus disease-19" OR "2019-nCoV disease" OR "2019 novel coronavirus disease" OR "2019-nCoV infection" OR "SARS COV-2" OR "SARS-COV-2" in combination with "Liver function" OR "AST" OR "ALT" OR "Liver toxicity" OR "Bilirubin" OR "SGOT" OR "Aspartate transaminase" OR "Alanine transaminase" OR "SGPT" OR "liver" OR "hepat*". A combination of keywords and free text was used to broaden the search result.

Inclusion Criteria

Observational studies in the English language, as well as articles in other languages with English abstracts, were assessed. Eligible studies were those that assessed the association between serum levels (ALT, AST, albumin, bilirubin, CRP, ESR, D-dimer, LDH) and severe outcomes of COVID-19 infection as the primary outcomes of main interest. Studies that reported medians and interquartile ranges (IQR) for AST, ALT, albumin, and bilirubin levels in both severe and non-severe COVID-19 infected patients were deemed eligible. Patient age was not considered as an exclusion criterion, however, studies on a particular group of individuals with specific conditions such as cirrhosis and tissue graft were excluded. Other publications such as case reports, articles on experts' opinions, letters to editors, review articles, books, and animal studies were also excluded. Identification of COVID-19 cases was based on the primary definition of the case study. The severity of COVID-19 infection was defined according to treatment guidelines by the Chinese National Institutes of Health. (20) Increased serum levels from laboratory data were defined as stated by the primary study classification.

Study Selection

Duplicated papers were excluded using the EndNote software X8 (Thomson Reuters, Philadelphia, USA). Two researchers (Malekan and Abounori) independently assessed all potential articles against the inclusion and exclusion Criteria of our study. Disagreement between the reviewers was resolved in consultation with a third researcher (Mortazavi). Initially, the titles and abstracts of the articles were screened based on our inclusion criteria. Then, the full text of the selected articles was reviewed based on both our inclusion and exclusion criteria to confirm study eligibility.

Quality Assessment

Two authors independently assessed the quality of the selected articles using the modified version of the Newcastle-Ottawa Scale (NOS). (21) The selection was based on comparability and exposure/outcome criteria and articles with a score of seven or higher were considered high-quality articles. The National Institutes of Health (NIH) quality assessment tool was used for case series studies and the articles were scored as acceptable, fair, or poor quality. (22)

Data Extraction

Two researchers (Malekan and Abounori) independently extracted the following information from the reelected articles: author's name, publication year, country, type of publication, study design, sample size, patients' characteristics, number of patients in severe and non-severe groups, number of discharged and admitted patients, number of deaths, and the mean (standard deviation( of laboratory data in severe and non-severe groups. Laboratory data included serum levels of CRP, D-dimer, ESR, LDH, AST, ALT, albumin, and bilirubin. The reported values for increased/decreased indices (CRP, ALT, AST, LDH, and D-dimer) were used as stated in the reference of the selected articles.

Statistical Analysis

The data were analyzed using the STATA software version 11.0 (Stata Corp LLC-United States). The heterogeneity between the articles was examined using I-square ([I.sup.2]) test. The random-effects model for [I.sup.2]>50% was used to pool the results. To identify the source of heterogeneity between the articles, subgroup analysis was performed based on the severity of the disease. Pooled prevalence and odds ratio (OR) were used to assess the outcomes.

Results

Selection Procedures

The search of Web of Science, Scopus, and Medline (via PubMed) databases identified 351 articles. A manual search of their references, using the Google Scholar search engine, yielded 643 additional articles. After excluding 341 duplicate articles, 653 articles were screened, out of which 92 articles were selected for full-text eligibility assessment. After excluding a further 50 articles, 42 studies were finally included in the meta-analysis. The PRISMA flow diagram of the study selection procedure is presented in figure 1.

A total of 6,557 confirmed cases of COVID-19 were reported in the 42 selected articles, and all studies were conducted in China (table 1). The overall quality of the included cross-sectional studies was acceptable and of the case series it was good. The quality assessment score of each study is presented in table 2.

Characteristics of the Patients

The age range of the patients was 1.5-90 years. The results showed that 19% of the patients had expired (figure 2), 80% required inpatient care services, 25% were admitted to the ICU (figure 3), and about 55% were discharged (figure 4).
Figure 2: The results of the meta-analysis showing the prevalence of 
mortality in all patients with COVID-19, categorized by disease 
severity. ES: Effect size
Study                                               ES (95% CI)
All patient
Huang Chaolin                                       0.15 (0.07, 0.28)
Guan Wei-jie                                        0.01 (0.01, 0.02)
Fu Hang                                             0.00 (0 00, 0.07)
Zhou Fei                                            0.28 (0.22, 0.35)
Chen Xu                                             0.01 (0.00, 0.02)
Chen Tao                                            0.41 (0.36, 0.47)
Chen Nanshan                                        0.11 (0.06, 0.19)
Ai Jinwei                                           0.03 (0.01, 0.08)
Wen Zhao                                            0.06 (0.03, 0.14)
Suochen Tian                                        0.00 (0.00, 0.10)
Lang Wang                                           0.19(0.15, 0.24)
Ying Huang                                          1.00 (0.90, 1.00)
Bicheng Zhang                                       1.00 (0.95, 1.00)
L. Zhang                                            0.29 (0 15, 0.47)
Xiao Tang                                           0.29 (0. 20, 0.40)
Chengfeng Qiu                                       0.01 (0.00, 0.05)
Suxin Wan                                           0.01 (0.00, 0.04)
Yonghao Xu                                          0.02 (0.00, 0.12)
Faling Zhou                                         0.14 (0.10, 0.20)
Qingxian Cai                                        0.01 (0.00, 0.02)
Yun Feng                                            0.08 (0.06, 0.11)
Dong Ji                                             0.01 (0.00, 0.03)
Subtotal ([IOTA]^2 = 99.97%, [rho] = 0.00)          0.19(0.01, 0.37)
Severe
Guan Wei-jie                                        0.08 (0.05, 0.13)
Zhou Fei                                            1.00 (0.93, 1.00)
Chen Xu                                             0.02 (0.00, 0.10)
Chen Tao                                            1.00 (0.97, 1.00)
Suxin Wan                                           0.03 (0.00, 0.13)
Ying Huang                                          1.00 (0.90, 1.00)
Bicheng Zhang                                       1.00 (0.95, 1.00)
Fan Yang                                            1.00 (0.96, 1.00)
Xiao Tang                                           0.29 (0.20. 0.40)
Yun Feng                                            0.06 (0.02, 0.15)
Subtotal ([IOTA] (^)2 = 99.87%, [rho] = 0.00}       0.55 (0.45, 0.66)
non-Severe
Guan Wei-jie                                        0.00 (0.00, 0,01)
Yun Feng                                            0.02 (0.01, 0.04)
Suxin Wan                                           0.00 (0.00, 0.04)
Subtotal ([IOTA] (^)2 = .%, p=.)                    0.00 (-0.00, 0.01)
Note: Table made from bar graph.
Figure 3: The results of meta-analysis showing the prevalence of ICU 
admission and admission of all patients with COVID-19. ES: Effect size
Study                                       ES (95% CI)
ICU admission
Huang, Chaolin                              0.32 (0.20, 0.47)
Guan, Wei-jie                               0.05 (0.04, 0.06)
Fu. Hang                                    0.06 (0.02, 0.16)
Zhou. Fei                                   0.26 (0.20, 0.33)
Chen, Nanshan                               0.23 (0.16, 0.32)
Ai. Jinwei                                  0.08 (0004, 0.15)
Wen Zhao                                    0.26 (0.17, 0.37)
Wang Wenjun                                 0.73 (0.43, 0.90)
Ying Huang                                  0.00 (0.00, 0.10)
Bicheng Zhang                               0.17 (0.10, 0.27)
L. Zhang                                    0.21 (0.10, 0.40)
Xiao Tang                                   1.00 (0.95, 1.00)
Jiaqiang Liao                               0.02 (0.00, 0.11)
Guo-Qing Qian                               0.10 (0.05, 0.18)
Chengleng Qiu                               0.09 (0.05, 0.16)
Suxin Wan                                   0.30 (0 23, 0.38)
Yanrong Wang                                0.04 (0.01, 0.12)
Yonghao Xu                                  1.00 (0.92, 1.00)
Fating Zhou                                 0.28 (0.23, 0.35)
Qingxian Cai                                0.10 (0.08, 0.14)
Yun Feng                                    0.11 (0.09, 0.15)
Zhichao Feng                                0.12 (0 10, 0.15)
Subtotal (l^2 -99.93%. p -0.00)             0.25 (0.03, 0.47)
Admission
Guan, Wei-jie                               0.94 (0.92, 0.95)
Fu. Hang                                    0.94 (0.84, 0.98)
Chen. Hujin                                 0.99 (0.69, 1.00)
Chen. Nanshan                               0.77 (0.68, 0.84)
Ai, Jinwei                                  1.00 (0.96, 1.00)
Zonghao Zhao                                1.00 (0 95, 1.00)
Wen Zhao                                    1.00 (0.95, 1.00)
Wang Wenjun                                 0.45 (0.21, 0.72)
Jiaqiang Liao                               0.22 (0.12, 0.36)
Guo-Oing Qian                               0.90 (0.82, 0.95)
Suxin Wan                                   0.89 (0.82, 0.93)
Jian Wu                                     0.76 (0.66, 0.84)
Yonghao Xu                                  1.00 (0.92, 1.00)
Yun Feng                                    0.05 (0 03, 0.07)
Zhichao Feng                                0.88 (0.85, 0.90)
Subtotal (l^2 = 99.85%. p = 0.00)           0.80 (0.69, 0.90)
Note: Table made from bar graph.


Laboratory Findings

Elevated levels of ALT, AST, and TBIL were reported in 20, 19, and 8 articles with the prevalence rates of 17% (95% CI: 13-21), 18% (95% CI: 14-23), and 12% (95% CI: 7-17), respectively (figures 5-7). Six articles examined reduced albumin levels with a prevalence of 44% (95% CI: 0-88) (figure 8).

Figure 9 shows the results of risk estimations from the random effects model combining the OR of laboratory findings between severe and non-severe patients. We noted an increase in CRP (OR=5.54, 95% CI: 2.67-11.49, [I.sup.2]=76.0%), ALT (OR=4.22, 95% CI: 1.01-17.66, [I.sup.2]=92.6%), AST (OR=4.96, 95% CI: 2.18-11.3, [I.sup.2]=82.6%), LDH (OR=4.13, 95% CI: 1.64-10.42, [I.sup.2]=67.8%), D-dimer (OR=4.34, 95% CI: 1.7-11.09, [I.sup.2]=86.9%), and Liver toxicity (OR=1.67, 95% CI: 0.20-15.86, [I.sup.2]=92.5%) (figure 10).

The most common observations from the laboratory findings of COVID-19 patients were increased ESR, CRP, LDH, and D-dimer levels reported in 9, 18, 18, and 17 articles, respectively. The meta-analysis of the results for CRP, LDH, ESR, and D-dimer was 57% (95% CI: 44-70), 53% (95% CI: 43-62), 36% (95% CI: 25-47) and 35% (95% CI: 24-47), respectively (figures 11-14).
Figure 4: The results of meta-analysis showing the prevalence of all 
discharged patients with COVID-19, categorized by disease severity. 
ES: Effect size
Study                                      ES <95% CI)
All patient
Guan Wei-jie                               0.05 (0.04. 0.06)
Fu Hang                                    1.00 (0 93. 1.00)
Chen Xu                                    0.55 (0.49. 0.60)
Chen Tao                                   0.59 (0.53. 0.64)
Chen Nanshan                               0.31 (0.23. 0.41)
Ai Jinwei                                  0.07 (0.03. 0.13)
Wen Zhao                                   0.83 (0.73. 0.90)
Lang Wang                                  0.81 (0.76. 0.85)
Bicheng Zhang                              0.23 (0.14. 0.36)
Ya-nan Han                                 1.00 (0.86.1.00)
Xiufs[pi]g Jiang                           1.00 (0.93. 1.00)
L. Zhang                                   0.36 (0.21. 0.54)
Xiao Tang                                  0.36 (0.26. 0.47)
Anjue Tang                                 0.65 (0.46. 0.81)
Jiaqiang Liao                              0.78 (0.64. 0.88)
Yun Feng                                   0.85 (0.81.0.88)
Guo-Qing Qian                              0.34 (0.25. 0.44)
Chengleng Qiu                              0.38 (0.30. 0.48)
S[upsilon]xm Wan                           0.11 (0.07. 0.18)
Yanrong Wang                               1.00(0.93. 1.00)
Jian Wu                                    0.26 (0.18. 0.37)
Faling Zhou                                0.86 (0.80. 0.90)
Yonghao Xu                                 0.24 (0.14. 0.39)
Subtotal (I (^)2 = 99.88%. p = O.OO)       0.55 (0.38. 0.72)
Severe
Guar Wei-jie                               0.03 (0.01. 0.07)
Chen Xu                                    0.58 (0.44. 0.71)
Chan Tao                                   0.00 (0.00. 0.03)
Suxin Wan                                  0.13(0.05. 0.26)
Xiao Tang                                  0.36 (0.26. 0.47)
Bicheng Zhang                              0.23 (0.14. 0.36)
Yun Feng                                   0.85 (0.73. 0.92)
Sha Fu                                     0.42 (0.29. 0.56)
Subtotal (l (^)2 = 98.52%. p = 0.00)       0.32 (0.19. 0.44)
non-Severe
Guan Wei-jie                               0.05 (0.04. 0.07)
Suxin Wan                                  0.11 (0.06, 0.18)
Yun Feng                                   0.95 (0.92. 0.97)
Xiufeng Jiang                              1.00 (0.92. 1.00)
Subtotal (l (^)2 = 99.97%. p = 0.00}       0.53 (-0.03. 1 09)
Note: Table made from bar graph.
Figure 5: The results of meta-analysis showing the prevalence of 
elevated ALT levels in all patients with COVID-19, categorized by 
disease severity. ES: Effect size
Study                                      ES (95% CI)
All patient
Guar. Wei-jie                              0.21 (0.19. 0.24)
Zhou. Fei                                  0.31 (0.25. 0.38)
Chen. Hujin                                0.33 (0.12. 0.65)
Chen. Xu                                   0.10 (0.07. 0.14)
Chen. Tao                                  0.22 (0.17, 0.27)
Chen. Nanshan                              0.28 (0.20. 0.38)
Ai. Jirv.vu:                               0.20 (0.13. 0.28)
Shen Xu                                    0.26 (0.21, 0.30)
Gemm Zhang                                 0.26 (0.19. 0,36)
Zonghao Zhao                               0.20 (0.13. 0.30)
Suochen Tian                               0.05 (0.01. 0.1B)
Anjue Tang                                 0.12 (0.04. 0.30)
Jiaqiang Liao                              0.15 (0.08. 028)
Guo-Qing Qian                              0.0B (0.04, 0,15)
                                           0.04 (0.01.0.10)
Faling Zhou                                0.18 (0.14. 024)
Qingxian Cai                               0.13 (0.10. 0.17)
Yun Feng                                   0.05 (0.04. 0.08)
Ya-nan Han                                 0.16 (0.06. 0.35)
Xiufeng Jiang                              0.25 (0.16. 0.38)
Subtotal (1^2 = 91.30%. p = 0.00)          0.17 (0.13. 0.21)
Severe
Guan. Wei-jie                              0.28 (0.21. 0.36)
Zhou. Fei                                  0.48 (0.35. 0.61)
Chen. Xu                                   0.20 (0.11, 0.33)
Chen. Tao                                  0.27 (0.19, 0.35)
Gemm Zhang                                 0.34 (0.20. 0.52)
Ying Huang                                 0.13 (0.05, 0.30)
Bicheng Zhang                              0.31 (0.21, 0.42)
Qingxian Cai                               0.95 (0.85. 0.99)
Yun Feng                                   0.59(0.46, 0,71)
Sha Fu                                     0.24 (0.14. 0.37)
Subtotal (l^2 = 97 47%. p = 0.00)          0.38 (0.18. 0.58)
non-Severe
GUAN Wei-jie                               0.20(0.17. 0,23)
Gemin Zhang                                0.22 (0.14, 0,34)
Dahai Zhao                                 0.28 (0.12, 0.51)
Qingxian Cai                               0.79 (0.65. 0.88)
Yun Feng                                   0.07 (0.04, 0.10)
Xiufe[pi]g Jiang                           0.30 (0.19, 0.44)
Subtotal (l (^)2 = 97 09%. p = 0.00)       0.30 (0.16. 0.44)
Note: Table made from bar graph.
Figure 6: The results of meta-analysis showing the prevalence of 
elevated AST levels in all patients with COVID-19, categorized by 
disease severity. ES: Effect size
Study                                      ES (95% CI)
All patient
Huang Chaolin                              0.37 (0.24.0.52)
Guan Wei-jie                               0.22 (0.19. 0.25)
Chen Xu                                    0.15 (0.11. 0.20)
Chen Tao                                   0.31 (0.25, 0.36)
Chen Nanshan                               0.35 (0.27.0.45)
Ai, Jinwei                                 0.25 (0.18. 0.35)
Shen Xu                                    0.29 (0.24. 0.34)
Gemin Zhang                                0.12 (0.07. 0.20)
Zonghao Zhao                               0.19(0.11,0.29)
Suochen Tian                               0.11 (0.04. 0.25)
Anjue Tang                                 0.12 (0.04. 0.30)
Jiaqia[pi]g Liao                           0.07 (0.02,0.18)
Guo-Qing Qian                              0.10(0.05. 0.18)
Suxin Wan                                  0.22 (0.16. 0.30)
Jian Wu                                    0.04 (0.01.0.10)
Fating Zhou                                0.22 (0.17. 0.29)
Qingxian Cai                               0.18(0.15, 0.22)
Yun Feng                                   0.06 (0.04. 0.08)
Ya-nan Han                                 0.20 (0.09. 0.39)
Subtotal (l (^)2 = 92.59%. p = 0.00)       0.18(0.14,0.23)
Severe
Chaolin Huang                              0.62 (0.36, 0.82)
Guar Wei-jie                               0.39 (0.32.0.48)
Chen Xu                                    0.32 (0.21. 0.46)
Chen Tao                                   0.52 (0.43. 0.61)
Suxin Wan                                  0.38 (0.24. 0.53)
Gemin Zhang                                0.16 (0.07. 0.32)
Ying Huang                                 0.58 (0.41. 0.74)
Bicheng Zhang                              0.61 (0.50, 0.72)
Qingxian Cai                               0.91 (0.78. 0.96)
Yun Feng                                   0.63 (0.50. 0.75)
Sha Fu                                     0.20 (0.11.0.33)
Subtotal (l^2 = 9-1.03%. p = 0.00)         0.48 (0.34. 0.63)
non-Severe
Chaolin Huang                              0.25 (0.13. 0.43)
Guan. Wei-jie                              0.18(0.15, 0.21)
Suxin Wan                                  0.16(0.10. 0.24)
Gemin Zhang                                0.10 (0.04. 0.19)
Dahai Zhao                                 0.28 (0.12.0.51)
Qingxian Cai                               0.57 (0.43, 0.70)
Yun Feng                                   0.07 (0.05. 0.10)
Xiufeng Jiang                              0.23 (0.14.0.37)
Subtotal (l^2 = 90.79%, p = 0.00)          0.21 (0.13, 0.29)
Note: Table made from bar graph.
Figure 7: The results of meta-analysis showing the prevalence of 
elevated bilirubin levels in all patients with covid-19, categorized 
by disease severity. ES: Effect size
Study                                      ES (95% CI)
All patient
Guan Wei-jie                               0.11 (0.00,. 0.13)
Chen Nanshan                               0.18 (0.12, 0.27)
Shen Xu                                    0.19 (0.15,0.23)
Zonghao Zhao                               0.16 (0.09,0.26)
Jiaqiang Liao                              0.15 (0.08, 0 28)
 Jian Wu                                   0.01 (0.00, 0.07)
Fating Zhou                                0.12(0.08, 0.17)
Xtufeng Jiang                              0.05 (0.02, 0.15)
Subtotal (l (^)2 = 90.69%, p = 0.00)       0.12 (0.07, 0.17)
Severe
Guan Wei-jie                               0.13(0 08, 0 20)
Chen Xu                                    0.12 (0.06, 0.24)
Yinn Huann                                 0.13 (0.05, 0 291
Bicheng Zhang                              0.31 (0.21, 0.42)
Subtotal (l (^)2 = 66.67%, p = 0.03)       0.17 (0.09, 0.25)
non-Severe
Guan Wei-jie                               0.10.(0.08, 0.13)
Xiufeng Jiang                              0.06 (0.02, 0.17)
Subtotal (l^2-.%. p =.)                    0.10.(0.07, 0.12)
Note: Table made from bar graph.
Figure 8: The results of meta-analysis showing the prevalence of 
decreased albumin levels in all patients with COVID-19. ES: Effect size
Sillily                                   ES (95% CI)
Chen Xu                                   0.25 (0.20. 0.30)
Chen Tao                                  0.35 (0.30, 0.41)
Chen Nanshan                              0.98 (0.93, 0.99)
Shen Xu                                   0.01 (0.01.0.03)
Ya-nan Han                                0.72 (0.52, 0.86)
Xiufeng Jiang                             0.33 (0.22, 0.46)
Overall (l (^)2 = 99.87%. p = 0.00)       0.44 (0.00, 0.88)
Note: Table made from bar graph.


Clinical Outcomes based on Disease Severity The prevalence of mortality in non-severe and severe COVID-19 patients was 0% (95% CI: 0-1) and 55% (95% CI: 45-66), respectively (figure 2, table 3).
Figure 9: The forest plot depicts the odds ratios of laboratory! 
findings.
Study
ID                                         OR (95% CI)
CRP Increase
Guan Wei-jie                               340.(2.15.540)
Gemin Zhang                                 28.16 (8.08, 98.09)
Jin-jin Zhang                                3.31 (0.69, 15.97)
Yun Feng                                     2.57 (1.38, 4.78)
Zhichao Feng                                 9.45 (4.43, 20.17)
Subtotal (l-squared = 76.0%. p = 0.002]      5.54 (2.67, 11.49)
ALT increase
Guan Wei-jie                                 1.59 (1.04, 2.43)
Gemin Zhang                                  1.83 (0.72, 4.70)
Qingxian Cai                               554 (1.14, 26.95)
Yun Feng                                    20.81 (10.46, 41.40)
Subtotal (l-squared = 92.6%, p = 0.000)      4.22 (1.01, 17.66)
AST increase
Chaolin Huang                                4.80 (1.18, 19.61)
 Guan Wei-jie                                2.92 (1.97, 434)
Gemin Zhang                                  1.76 (0.49,6.28)
Qingxian Cai                                 7.22 (2.22. 23.51)
Yun Feng                                    22.24 (11.20. 44.15)
Suxin War                                    3.20 (1.37, 745)
Subtotal (l-squared = 82.6%, p = 0.000)      4.96 (2.18, 11.30)
LDH increase
Chaolin Huang                                7.06 (0.79, 62.72)
Guan Wei-jie                                 2.34 (1.58, 3.48)
Suxin Wan                                    7.18 (3.10, 16.64)
Subtotal (l-squared = 67.8%.                 4.13 (1.64, 10.42)
 p = 0.045)
D-dlmer increase
GuanWei-jie                                  1.94 (1.27, 2.97)
Gemin Zhang                                 41.17 (12.12, 139.85)
Jin-jin Zhang                                3.96 (1.56, 10.05)
Zhichao Feng                                 2.11 (1.25, 3.56)
Subtotal (l-squared = 86.9%. p = 0.000)      4.34 (1.70, 11.09)
Liver toxicity
Wen Zhao                                     0.55 (0.18, 1.63)
Qingxian Cai                                 5.09 (3.04, 8.52)
Subtotal (l-squared = 92.5%. p = 0.000)      1.76 (0.20,15.86)
Note: Table made from bar graph.
Figure 10: The results of meta-analysis showing the prevalence of 
liver toxicity levels in all patients with COVID-19, categorized by 
disease severity. ES: Effect size
Study                                      ES (95% CI)
All patient
Fu Hang                                    0.19(0.11,0.32)
Chen Tao                                   0.05 (0.03. 0.08)
Gemin Zhang                                0.53 (0.43. 0.62)
Wen Zhao                                   0.32 (0.23. 0.44)
Lang Wang                                  0.28 (0.24. 0.33)
Wang Wenjun                                0.55 (0.28, 0.79)
Chengfeng Qiu                              0.05 (0.02. 0.11)
Qiao Shi                                   0.18 (0.12. 0.26)
Jian Wu                                    0.04 (0.01,0.10)
Hanshena Xia                               0.37 (0.72, 0.48)
Yonghao xu                                 0.38 (0.25, 0.52)
Fating Zhou                                0.04 (0.02, 0.08)
Qingxian Cai                               0.05 (0.04, 0.08)
Subtotal (l^2 = 95.35%, p = 0.00)          0.20.(0.14, 0.26)
Severe
Chen Tao                                   0.09 (0.05, 0.16)
Wen Zhao                                   0.30 (0.15, 0.52)
Ying Huang                                 0.61 (0.45. 0.75)
Bicheng Zhang                              0.78 (0.68, 0.86)
Xiao Tang                                  0.45 (0.34, 0.57)
Qingxian Cai                               0.46 (0.36. 0.56)
Fan Yang                                   0.16 (0.10. 0.25)
Subtotal (l (^)2 = 97.23%, p = 0.00]       0.41 (0.19, 0.62)
 non-Severe
Wen Zhao                                   0.44 (0.32. 0.57)
Qingxian Cai                               0.14(0.11.0.19)
Subtotal (l (^)2 = .%, p = .)              0.17(0.13, 0.20)
Note: Table made from bar graph.
Figure 11: The results of meta-analysis showing the prevalence of 
elevated CRP levels in all patients with COVID-19, categorized by 
disease severity. ES: Effect size
Study                                     ES (95% CI)
All patient
Guan Wei-jie                              0.61 (0.57, 0.64)
Chen Hujin                                0.67 (0.35, 0.88)
Chen Xu                                   0.50.(0.44, 0.56)
Chen Tao                                  0.33 (0.27, 0.39)
Chen Nanshan                              0.[THETA]6 (0.77, 0.92)
Ai Jtnwei                                 0.68 (0.58, 0.76)
Zonghao Zhao                              0.61 (0.50, 0.72)
Suochen Tian                              0.51 (0.36, 0.67)
Jin-JIN Zhang                             0.92 (0.86, 0.95)
L. Zhang                                  0.82 (0.64, 0,92)
Anjue Tang                                0.19 (0.09, 0.38)
Jiaqiang Liao                             0.20.(0.11, 0.33)
Guo-Qing Qian                             0.54 (0.44, 0.64)
Yantong Wang                              0.18 (0.10, 0.30)
Yun Feng                                  0.56 (0.51, 0.60)
Zhichao Feng                              0.51 (0.47, 0.55)
Ya-nan Han                                0.44 (0.27, 0.63)
Xiufeng Jiang                             0.36 (0.25, 0.50)
Subtotal (l (^)2 = 96.66%, p = 0.00)      0.53 (0.43, 0.62)
Severe
Guan Wei-jie                              0.81 (0.74, 0.87)
Chen Tao                                  0.60.cents0.5[theta]! 0.69)
Gemin Zhang                               0.66 (0.48, 0.80)
Ying Huang                                0.97 (0.85, 0.99)
Bicheng Zhang                             1.00.(0.95, 1.00)
Jin-jin Zhang                             0.96 (0.88, 0.99)
Yun Feng                                  0.70.(0.57, 0.81)
Zhichao Feng                              0.88 (0.79, 0.94)
Sha Fu                                    0.42 (0.29, 0,56)
Subtotal (l (^)2 = 96.07%. p = 0.00]      0.78 (0.69, 0.88)
non-Severe
Guan Wei-jie                              0.56 (0.53, 0.60)
Gemin Zhang                               0.06 (0.02, 0.15)
Jin-jin Zhang                             0.89 (0.80, 0.94)
Dahai Zhao                                0.95 (0.75, 0.99)
Yun Feng                                  0.48 (0.43, 0.53)
Zhichao Feng                              0.45 (0.41. 0.50)
Xiufeng Jiang                             0.43 (0.30, 0.57)
Subtotal (I (^)2 = 93.57%. p = 0.00)      0.55 (0.36, 0.73)
Note: Table made from bar graph.
Figure 12: The results of meta-analysis showing the prevalence of 
elevated LDH levels in all patients with COVID-19, categorized by 
disease severity. ES: Effect size
Study                                      ES (95% CI)
All patient
Huang Chaolin                              0.73 (0.57, 0.84)
Guan Wei-jie                               0.41 (0.37, 0.45)
Zhou Fei                                   0.67 (0.60, 0.73)
Chen Xu                                    0.15(0.11,0.20)
Chen Tao                                   0.42 (0.37, 0.48)
Chen, Nanshan                              0.76 (0.66. 0.83)
Ai Jinwei                                  0.36 (0.28, 0.46)
Shen Xu                                    0.46 (0.41, 0.51)
Zonghao Zhao                               0.44 (0.33, 0.55)
Suochen Tian                               0.16(0.08, 0.31)
Anjue Tang                                 0.46 (0.29, 0.65)
Jiaqiang Liao                              0.20 (0.11, 0.33)
Yanrong Wang                               0.24 (0.14. 0.36)
Jian Wu                                    0.21 (0.14, 0.31)
Fating. Zhou                               0.33 (0.27, 0.40)
Dong Ji                                    0.03 (0.01, 0.06)
Ya-nan Han                                 0.04 (0.01, 0.20)
Suxin Wan
                                           0.43 (0.35, 0.51)
Subtotal (l^2 = 98.23%. p = 0.00)          0.36 (0.25, 0.47)
Severe
Chaolin Huang                              0.92 (0.67, 0.99)
Guan Wei-jie                               0.58 (0.49, 0.66)
Zhou Fei                                   0.98 (0.90. 1.00)
Chen Xu
                                           1.48 (0.35, 0.61)
Chen Tao                                   0.82 (0.74, 0.88)
Suxin Wan                                  0.75 (0.60, 0.86)
Ying Huang                                 1.00 (0.86, 1.00)
Bicheng Zhang                              0.93 (0.85, 0.97)
Sha Fu                                     0.22 (0.13, 0.35)
Subtotal (l (^)2 - 97.36%. p = 0.00)       0.75 (0.62. 0.87)
non-Severe
Chaolin Huang                              0.63 (0.44, 0.78)
Guan Wei-jie                               0.37 (0.33, 0.41)
Dahai Zhao                                 0.32 (0.15, 0.54)
Suxin Wan                                  0.29 (0.21, 0.39)
Subtotal (l^2 = 71.85%.                    0.39 (0.28, 0.49)
p = 0.01)
Note: Table made from bar graph.


Laboratory Findings Related to Disease Severity

The prevalence rate of increased ALT and AST levels was 30% and 21% in the non-severe and 38% and 48% in the patients with severe COVID-19 infection, respectively (figures 6 and 7, table 3).

Elevation of CRP, LDH, D-dimer, and bilirubin levels was found in 78%, 75%, 79%, and 17% of the severe cases compared to 55%, 39%, 28%, and 10% of the non-severe cases, respectively. A decrease in albumin levels occurred in 36% of the severe patients (figures 7, 11, 12, 14). Only one article reported a 29% decrease in albumin levels in non-severe patients. (58) Liver toxicity affected 41% of the severe and 17% of the non-severe cases (figure 10, table 3).

Discussion

In a systematic review and meta-analysis, patients with severe and non-severe COVID-19 infection were compared. The results showed elevated ALT, AST, LDH, D-dimer, CRP, and TBIL levels and lower levels of albumin.

Previous studies reported that small amounts of ACE2 receptors are expressed in the human hepatocyte, (60,) (61) indicating an insignificant effect of SARS-CoV-2 infection on liver function in non-severe and mild cases. (17,) (62) Recent studies have reported the incidence of liver damage in severe cases of COVID-19, mostly with elevated levels of ALT, AST, LDH, CRP, D-dimer, TBIL, and low levels of albumin. (8,17,) (45,) (62,) (63) It is also reported that higher levels of D-dimer, CRP, and AST are related to the severity of COVID-19 infection. (17) A previous study on deceased cases of COVID-19 with liver abnormalities reported that ALT, AST, and TBIL levels were higher than the normal levels in patients with severe complications. TBIL was also reported to be lower than the upper limit of the normal range. (59) Other studies have reported lower albumin levels in severe cases. (17,) (64) Hypoalbuminemia is mainly due to inadequate nutrition intake and overconsumption of protein during hospitalization. (62) Elevated AST, ALT, and TBIL serum levels and reduced levels of albumin have been observed in severe cases. In a retrospective study, (15) the meta-analysis of AST (95% CI: 5.97 to 11.71, [I.sup.2]=73.4%), ALT (95% CI: 4.77 to 9.93, [I.sup.2]=57.2%), TBIL (95% CI: 1.24 to 3.36, [I.sup.2]=68.8%), and albumin (95% CI: -6.20 to -2.28, [I.sup.2]=95.7%) levels were different compared to our results. In the present study, the metaanalysis of AST (95% CI:14-23, [I.sup.2]=94.03%), ALT (95% CI: 13-21, [I.sup.2]=97.47%), and TBIL (95% CI: 7-17, [I.sup.2]=66.67%), and albumin (95% CI: 0-88, [I.sup.2]=0%) levels in severe cases produced better results (except for albumin) due to the inclusion of a higher number of studies.
Figure 13: The results of meta-analysis showing the prevalence of 
elevated ESR levels in all patients with COVID-19. ES: Effect size
Study                           ES (95% CI)
Chen Xu                         0.58 (0.53, 0.64)
Chen Nanshan                    0.85 (0.76, 0.91)
Ai Jinwei                       0.58 (0.47, 0.68)
Zonghao Zhao                    0.40 (0.30, 0.51)
Suochen Tian                    0.65 (0.49, 0.78)
L. Zhang                        0.57 (0.39, 0.73)
Anjue Tang                      0.27 (0.14, 0.46)
Yanrong Wang                    0.36 (0.25, 0.50)
Ya-nan Han                      0.84 (0.65, 0.94)
Overall (l (^)2 = 91.90%,       0.57 (0.44, 0.70)
p = 0.00)
Note: Table made from bar graph.
Figure 14: The results of meta-analysis showing the prevalence of 
elevated D-dimer levels in all patients with COVID-19, categorized by 
disease severity. ES: Effect size
Study                                      ES (95% CI)
All patient
Guan Wei-jie                               0.22 (0.17, 0.27)
Zhou Fei                                   0.68 (0.61, 0.75)
Chen Tao                                   0.15 (0.11, 0.20)
Chen Nanshan                               0.36 (0.28, 0.46)
Shen Xu                                    0.72 (0.67, 0.76)
Gemin Zhang                                0.66 (0.56, 0.75)
Suochen Tian                               0.19 (0.09, 0.34)
Jin-jin Zhang                              0.43 (0.33, 0.54)
L. Zhang                                   0.39 (0.24, 0.58)
Jiaqiang Liao                              0.15 (0.08, 0.28)
Guo-Qing Qian                              0.24 (0.17, 0.34)
Jian Wu                                    0.04 (0.01, 0.10)
Fating Zhou                                0.47 (0.40, 0.54)
Zhichao Feng                               0.48 (0.44, 0.52)
Dong Ji                                    0.21 (0.16, 027)
                                           0.28 (0.14, 0.48)
Xiufeng Jiang                              0.27 (0.17, 0.40)
Subtotal (l (^)2 = 97.97%. p - 0.00)       0.35 (0.24, 0.47)
Severe
Guan Wei-jie                               0.60 (0.50, 0.68)
Zhou Fei                                   0.93 (0.82, 0.97)
Chen Xu                                    0.88 (0.76, 0.94)
Gemin Zhang                                0.81 (0.65, 0.91)
Ying Huang                                 1.00 (0.87, 1.00)
Bicheng Zhang                              0.97 (0.90, 0.99)
Zhichao Feng                               0.64 (0.52, 0.74)
Sha Fu                                     0.62 (0.48, 0.74)
Subtotal (l (^)2 = 94.70%. p = 0.00)       0.79 (0.70, 0.89)
non-Severe
Guan, Wei-jie                              0.43 (0.39, 0.48)
Gemin Zhang                                0.10 (0,04, 0.19)
Jin-jin Zhang                              0.28 (0.17, 0.43)
Zhichao Feng                               0.45 (0.41, 0.50)
Dong Ji                                    0.17 (0.12, 0.23)
Xiufeng Jiang                              0.21 (0.12, 0.35)
Subtotal (l"2 = 96.07%. p = 0,00)          0.28 (0.14,041)
Note: Table made from bar graph.


Another systematic review and meta-analysis of articles on liver manifestations of COVID-19 reported elevated levels of AST (95% CI: 13.6-16.5) and ALT (95% CI: 13.6-16.4) in 15% of the infected patients. (10) An increase in TBIL levels was also reported in 16.7% of patients (95% CI: 15.0-18.5). Such increases in the upper limit of the normal range were attributed to drug or virus-induced hepatic injury. Moreover, drug-induced hepatotoxicity with remdesivir and favipiravir was also reported. Notably, liver injury due to lopinavir/ritonavir has not been observed in COVID-19 patients. Furthermore, liver injury due to chloroquine and hydroxychloroquine is rarely reported. The main limitation of the above-mentioned study is the absence of a comparison of elevated levels between non-severe and severe cases.

Wu and colleagues reported elevated LDH levels in COVID-19 patients with severe pneumonia. (65) LDH is an essential element in glucose metabolism and its activity is widespread in numerous body tissues, especially in myocardial and liver cells. LDH is released in cells when the cytoplasmic membrane is damaged. (34) In previous studies on SARS and MERS, elevated LDH levels were also observed. Therefore, it can be concluded that LDH can independently act as a risk factor with poor clinical outcomes, which calls for further research. (45,) (49) Increased levels of LDH might be caused by a broader expression of ACE2 receptors in cardiac blood vessels. (60,) (66) It is also attributed to myositis induced by virus infection.(68) Moreover, since ACE2 receptors are present in hepatocytes, LDH levels will increase due to hepatocyte injuries. This clarifies the fact that liver or cardiac damage could occur as a direct effect of SARS-Cov-2 on targeted organs. (34) Therefore, elevated LDH enzymes in severe cases might occur as a result of direct hepatic or extra-hepatic damage.

Our results showed that the likelihood of developing liver toxicity as a complication of COVID-19 was 1.76 times higher in severely infected patients. Liver toxicity (hepatotoxicity) is the leading systemic toxicity of drugs and chemicals that commonly occurs in clinical practice. (67) Many drugs used to treat COVID-19 patients can also damage the liver. For example, lopinavir/ritonavir is associated with a seven-fold increased risk of liver injury and might cause liver damage and adversely affect liver function tests. (63,) (68) Other drugs used in the treatment of COVID-19 patients (e.g., antibiotics, antiviral agents, and steroids) might also potentially result in liver damage. Although these adverse effects require further clarification, (69) more attention should be paid to drug-induced liver damage in hospitalized patients. In general, elevated liver enzymes during hospitalization could be caused by such drugs and the observed abnormalities in liver function tests might be due to sepsis or shock. (54)

Like SARS-CoV, SARS-CoV-2 could affect lymphocytes, especially T lymphocytes. (34) Patients with damaged T cells are more vulnerable to infections and are at increased risk for severe illness. We found that CRP levels were higher in severe than non-severe patients and a CRP level >100 mg/dl could be indicative of bacterial infection. CRP level can be used as a prognostic factor, since it may also indicate the risk for other infections (mostly opportunistic infections) that could negatively affect the liver or lead to hepatitis. (69-72) On the other hand, cytokine profiles marked by higher concentrations of CRP, ESR, ferritin, and hs-CRP are associated with the severity of COVID-19. As a result, elevated cytokine factors in the blood might suggest pro-inflammatory cytokines (cytokine storm). (18)

Sepsis is another severe complication in COVID-19 patients, which is associated with some clinical symptoms and laboratory manifestations. Laboratory data analysis mostly revealed hyperbilirubinemia, acidosis, high lactate, coagulopathy, and thrombocytopenia in COVID-19 patients in the ICU. (73,) (74) As mentioned above, sepsis is one of the causes of liver injury during infection with SARS-Cov-2.

Aberrant coagulation has been suggested in the case of abnormal laboratory findings in severely affected patients. (75) Furthermore, some recent studies have revealed that COVID-19 is associated with disseminated intravascular coagulation (DIC) (76) and subsequent consumption coagulopathy. (77) D-dimer is a fibrin degradation product, which can be significantly elevated in patients with DIC. (78) Significant increase in D-dimer level can also occur in patients with liver cirrhosis and progressively increase as the degree of liver dysfunction becomes more severe. (79,) (80) Overall, higher levels of D-dimer of hepatic or extra-hepatic origin could be used as a prognostic factor for COVID-19. However, it has been reported that individual liver indices such as ALT, AST, TBIL, alkaline phosphatase (ALP), albumin, globulin, international normalized ratio (INR), LDH, and CRP did not have an association with the severity of COVID-19. (62)

To sum up, in this systematic review and meta-analysis, we established that there is an interrelationship between the level of abnormality in liver markers and the severity of COVID-19 infection. Elevated levels of ALT, AST, LDH, CRP, D-dimer, TBIL, and lower levels of albumin could be prognostic factors for COVID-19 patients when they occur concomitantly rather than individually.

Although most included articles were of acceptable quality, the main limitation of the present study is the inclusion of studies from China only, which may undermine the generalizability of our findings. It is therefore recommended to include studies from other countries in future research.

Conclusion

Elevation of liver function tests was higher in patients with severe than non-severe cases of COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevated liver function tests in COVID-19 patients across the globe. Further research is recommended to identify the main factors associated with elevated levels of liver enzymes to determine whether the effect is directly or indirectly due to the virus or drug toxicity.

Acknowledgment

The authors would like to express their gratitude for the support from the Student Research Committee of Mazandaran University of Medical Sciences, Sari, Iran. The study was approved by the Ethics Committee of the University (code: IR.MAZUMS.REC.1399.049).

Conflict of Interest: None declared.

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Mohammad Zahedi (1), BSc;(iD) Mohammad Yousefi (2), MD; Mahdi Abounoori (3), MD; Mohammad Malekan (3), MD; Fatemeh Tajik (4), MD; Keyvan Heydari (5), MD; Parham Mortazavi (6), PharmD; Sulmaz Ghahramani (7), PhD; Monireh Ghazaeian (8), PhD; (iD) Fateme Sheydaee (2), MD; Amirreza Nasirzadeh (9), BSc; Reza Alizadeh-Navaei (5), PhD

(1)Department of Laboratory Sciences, School of Allied Medical Science, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran;

(2)Department of Medicine, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran;

(3)Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;

(4)Department of Medicine, School of Medicine, Azad University of Tehran, Tehran, Iran; (5)Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran;

(6)Student Research Committee, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;

(7)Health Policy Research Center, Institute of Health, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;

(8)Department of Clinical Pharmacy, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;

(9)Student of Basic Sciences in Nursing, Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran

Correspondence:

Monireh Ghazaeian, PhD; School of Pharmacy, Mazandaran University of Medical Sciences, 17 (th) Km of Khazar Abad Road, Postal code: 48178-44718, Sari, Iran

Tel: +98 11 33257230

Fax: +98 11 33261244

Email: ghazaeianm@gmail.com

Received: 01 August 2020

Revised: 18 October 2020

Accepted: 16 January 2021

What's Known

* Elevated serum levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin, and low albumin levels are observed in patients with severe COVID-19 infection.

* In addition to elevated liver enzymes, patients with liver damage have an increased level of biomarkers such as D-dimer, erythrocyte sedimentation rate, C-reactive protein, and lactate dehydrogenase.

What's New

* Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection.

* Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients.

Please cite this article as: Zahedi M, Yousefi M, Abounoori M, Malekan M, Tajik F, Heydari K, Mortazavi P, Ghahramani S, Ghazaeian M, Sheydaee F, Nasirzadeh AR, Alizadeh-Navaei R. The Interrelationship between Liver Function Test and the Novel Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. Iran J Med Sci. 2021;46(4):237-255. doi: 10.30476/ijms.2021.87555.1793.
Table 1: Detailed characteristics of the included articles.
Author        Country   Type of      Sample         Mean Age
                        study        size (male/female)
Huang         China     C/S          41 (30/11)      49.0
et al. (2)                                          (41.0-58.0)
Guan          China     C/S          1,099           47.0
et al. (23)                          (637/459)      (35.0-58.0)
Fu            China     C/S          52 (28/24)      44.5
et al. (24)                                         (33.0-56.5)
Zhou          China     C/S          191 (119/72)    56.0
et al. (25)                                         (46.0-67.0)
Chen          China     Case         9 (0/9)         29.9
et al. (26)             series
Chen          China     C/S          291             46.0
et al. (27)                          (145/146)      (34.0-59.0)
Chen          China     C/S          274             62.0
et al. (28)                          (171/103)      (44.0-70.0)
Chen          China     C/S          99 (67/32)      55.5
et al. (29)                                         (21.0-82.0)
Ai            China     C/S          102 (52/50)     50.4
et al. (30)                                          (1.5-90.0)
Xu            China     C/S          355            -
et al. (31)                          (162/193)
Zhang         China     C/S          95 (42/53)      49.0
et al. (32)                                         (39.0-58.0)
Zhao          China     C/S          75 (33/42)      47.0
et al. (5)                                          (34.0-55.0)
Zhao          China     C/S          77 (34/43)      52.0
et al. (33)
Tian          China     C/S          37 (17/20)      44.3
et al. (34)
Wang          China     C/S          339             71.0
et al. (35)                          (166/173)
Wang          China     C/S          11 (10/1)       58.0
et al. (3S)                                         (49.0-72.0)
Huang         China     C/S          36 (25/11)      69.2
et al. (37)
Zhang         China     C/S          82 (54/28)      72.5
et al. (38)
Zhang         China     C/S          140 (71/69)     57.0
et al. (39)
Zhang         China     C/S          28 (17/11)      65.0
et al. (40)
Zhao          China     C/S          34(11/8)        48.0
et al. (41)
Tang          China     C/S          73 (45/28)      67.0
et al. (42)
Tang          China     C/S          26 (17/9)        6.9
et al. (43)
Liao          China     C/S          46 (24/22)     -
et al. (44)
Qian          China     C/S          91 (37/54)      50.0
et al. (45)                                         (36.5-57.0)
Qiu           China     C/S          104 (49/55)     43.0
et al. (46)
Shi           China     C/S          101 (60/41)    -
et al. (47)
Wan           China     C/S          135 (72/63)     47.0
et al. (48)                                         (36.0-55.0)
Xu            China     C/S          55 (22/33)      49.0
et al. (49)                                          (2.0-69.0)
Wu            China     C/S          80 (39/41)      46.1
et al. (50)
Xie           China     C/S          79 (44/35)      60.0
et al. (51)                                         (48.0-66.0)
Xu            China     C/S          45 (29/16)      56.7
et al. (52)
Zhou          China     C/S          191 (119/72)    56.0
et al. (25)                                         (46.0-67.0)
Zhou          China     C/S          197 (99/98)     55.9
et al. (53)
Cai           China     C/S          417             47.0
et al. (54)                          (198/219)      (34.0-60.0)
Feng          China     C/S          476             53.0
et al. (17)                          (271/205)      (40.0-64.0)
Feng          China     C/S          564             47.0
et al. (55)                          (284/280)      (36.0-58.0)
Fu            China     C/S          50 (27/23)     -
et al. (18)
Ji            China     C/S          208 (117/91)    44.0
et al. (56)
Han           China     C/S          25 (12/13)      44.0
et al. (57)                                         (22.0-70.0)
Jiang China   C/S       55 (27/28)    45.0          -
et al. (58)                          (27.0-60.0)
Yang China    C/S       92           -              15
et al. (59)
Author        Number of        CRP           Serum levels (ALT:
              patients with    (mg/l)        U/L, AST: U/L,
              liver toxicity                 Bilirubin: mg/dL.
                                             Albumin: g/L)
Huang         -                 -            ALT: 32.0 (21.0-50.0)
et al. (2)                                   AST: -
                                             Bilirubin: -
                                             Albumin: 31.4
                                             (28.9-36.0)
Guan          -                 -            ALT: -
et al. (23)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Fu            10                 8.8         ALT: 24.0 (15.3-39.0)
et al. (24)                     (3.5-21.4)   AST: 27.0 (21.2-34.0)
                                             Bilirubin: -
                                             Albumin: -
Zhou          _                 _            ALT: 30.0 (17.0-46.0)
et al. (25)                                  AST: -
                                             Bilirubin: -
                                             Albumin: 32.3
                                             (29.1-35.8)
Chen          -                 18.61        ALT: 253.8
et al. (26)                                  AST: 171.0
                                             Bilirubin: -
                                             Albumin: -
Chen          _                 15.6         ALT: 20.7 (14.9-28.9)
et al. (27)                     (4.4-30.3)   AST: 24.7 (19.9-31.4)
                                             Bilirubin: 27.0
                                             Albumin: 37.3
                                             (34.7-40.3)
Chen          13                53.4         ALT: 23.0 (15.0-38.0)
et al. (28)                    (18.6-        AST: 30.0 (22.0-46.0)
                               113.0)        Bilirubin: -
                                             Albumin: 33.9
                                             (30.3-37.6)
Chen          _                 51.4         ALT: 39.0 (22.0-53.0)
et al. (29)                                  AST: 34.0 (26.0-48.0)
                                             Bilirubin: 15.1
                                             Albumin: 31.6
Ai            _                 28.2         ALT: 27.8
et al. (30)                                  AST: 30.6
                                             Bilirubin: -
                                             Albumin: -
Xu            -                              ALT: 35.0 (1.0-414.0)
et al. (31)                                  AST: 40.76
                                             (10.0-475.0)
                                             Bilirubin: 14.16
                                             (0.7-511.6)
                                             Albumin: 38.5
                                             (18.2-56.1)
Zhang         50                25.0         ALT: -
et al. (32)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Zhao          -                 13.6         ALT: 23.0 (14.0-43.0)
et al. (5)                      (3.8-48.2)   AST: 27.0 (21.0-37.0)
                                             Bilirubin: 14.5
                                             (11.1-18.2)
                                             Albumin: -
Zhao          25                17.0         ALT: 28.0 (20.0-46.0)
et al. (33)                     (4.6-51.1)   AST: 29.0 (21.0-42.0)
                                             Bilirubin: -
                                             Albumin: -
Tian                                         ALT: -
et al. (34)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Wang          96                49.6         ALT: 27.0 (17.0-44.0)
et al. (35)                    (18.5-        AST: 32.0 (23.0-46.0)
                                93.2)        Bilirubin: -
                                             Albumin: -
Wang          6                 12.1         ALT: 24.0 (15.9-27.7)
et al. (3S)                     (6.2-13.7)   AST: -
                                             Bilirubin: 15.1
                                             (11.2-20.4)
                                             Albumin: 33.6
                                             (30.5-37.2)
Huang         22               106.2         ALT: 26.0 (18.0-38.0)
et al. (37)                    (60.8-        AST: 43.0 (30.0-51.0)
                               225.3)        Bilirubin: 11.2
                                             (7.5-19.2)
                                             Albumin: 30.2
Zhang         64                11.7         ALT: 26.0 (18.5-47.5)
et al. (38)                    (63.3-        AST: 72.0 (30.0-71.0)
                               186.6)        Bilirubin: 13.6
                                             (10.0-22.9)
                                             Albumin: 33.1
                                             (30.3-36.9)
Zhang         -                 34.2         ALT: -
et al. (39)                    (12.5-        AST: -
                                67.4)        Bilirubin: -
                                             Albumin: -
Zhang         -                -             ALT: -
et al. (40)                                  AST: -
                                             Bilirubin: -
                                             Albumin: 31.1
                                             (28.6-34.8)
Zhao          -                 26.5         ALT: 36.4 (11.8-85.0)
et al. (41)                    (10.0-        AST: 34.9 (17.6-103.8)
                               127.1)        Bilirubin: -
                                             Albumin: -
Tang          33                87.2         ALT: 34.5 (24.0-61.0)
et al. (42)                    (32.6-        AST: 25.5 (20.0-42.5)
                               104.5)        Bilirubin: 9.8 (8.0-14.5)
                                             Albumin: 33.2
                                             (30.8-36.2)
Tang          -                -             ALT: -
et al. (43)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Liao          -                  2.6         ALT: 17.9 (11.6-32.5)
et al. (44)                     (0.8-9.4)    AST: 18.3 (14.5-26.9)
                                             Bilirubin: 8.7 (5.9-14.6)
                                             Albumin: -
Qian          -                  6.8         ALT: 18.0 (13.0-28.0)
et al. (45)                     (1.9-15.3)   AST: 21.0 (17.0-28.0)
                                             Bilirubin: -
                                             Albumin: 40.0
                                             (37.8-42.0)
Qiu           5                 11.7         ALT: 20.0 (15.0-34.2)
et al. (46)                     (3.5-32.7)   AST: 26.0 (20.8-34.1)
                                             Bilirubin: 10.9
                                             (7.5-16.6)
                                             Albumin: 37.3
Shi           18               107.9         ALT: 56.0          -
et al. (47)                                  AST: 116.8
                                             Bilirubin: 25.0
                                             Albumin: -
Wan           -                 10.5         ALT: 26.0 (12.9-33.1)
et al. (48)                     (2.7-51.2)   AST: 33.4 (27.8-43.7)
                                             Bilirubin: 8.6 (5.9-13.7)
                                             Albumin: 40.5 (37-43.4)
Xu            -                -             ALT: -
et al. (49)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Wu            3                  6.6         ALT: 24.0 (12.0-38.0)
et al. (50)                     (5.3-12.3)   AST: 30.0 (19.0-39.0)
                                             Bilirubin: 6.6 (5.4-12.0)
                                             Albumin: 38.3
                                             (37.0-46.2)
Xie           29                13.9         ALT: 34.0 (18.0-67.0)
et al. (51)                     (3.1-51.9)   AST: 30.0 (23.0-50.0)
                                             Bilirubin: 13.6
                                             (8.8-17.6)
                                             Albumin: -
Xu            17                             ALT: 29.0 (20.1-50.0)
et al. (52)                                  AST: 27 (22.0-39.5)
                                             Bilirubin: 15.5
                                             (10.5-21.3)
                                             Albumin: 31.6
                                             (30.2-34.5)
Zhou                                         ALT: 30.0 (17.0-46.0)
et al. (25)                                  AST: -
                                             Bilirubin: -
                                             Albumin: 32.3
                                             (29.1-35.8)
Zhou           8                55.0         ALT: 38.4
et al. (53)                                  AST: 38.8
                                             Bilirubin: 16.3
                                             Albumin: -
Cai           22                             ALT: 21.0 (15.0-31.0) -
et al. (54)                                  AST: 26.5 (21.0-35.0)
                                             Bilirubin: -
                                             Albumin: -
Feng          -                 18.8         ALT: -
et al. (17)                     (5.2-57.0)   AST: -
                                             Bilirubin: 10.1
                                             (7.5-14.0)
                                             Albumin: 37.9
                                             (32.8-41.8)
Feng                                         ALT: 20.3 (15.0-30.4)
et al. (55)                                  AST: 24.3 (19.5-31.5)
                                             Bilirubin: 11.9
                                             (8.7-17.6)
                                             Albumin: 39.0
                                             (35.7-42.4)
Fu            -                              ALT: -
et al. (18)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Ji                                           ALT: 24.0 (14.0-37.3)
et al. (56)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Han           -                              ALT: -
et al. (57)                                  AST: -
                                             Bilirubin: -
                                             Albumin: -
Jiang China    8.8                           ALT: 21.0 (16.0-48.0) -
et al. (58)   (3.5-21.4)                     AST: 24.0 (20.0-32.0)
                                             Bilirubin: 7.0 (4.0-10.0)
                                             Albumin: 42.0
                                             (39.0-45.0)
Yang China    15.6                           ALT: -
et al. (59)   (4.4-30.3)                     AST: -
                                             Bilirubin: -
                                             Albumin: -
Author        LDH             D-dimer        ESR       Diagnosis
              (U/L)           ([micro]g/mL)  (mm/h)    method
Huang          286.0           0.5           -         RT-PCR
et al. (2)    (242.0-408.0)   (0.3-1.3)
Guan          -               -              -         RT-PCR
et al. (23)
Fu             224.0           0.7           -         RT-PCR
et al. (24)   (200.0-253.0)   (0.5-0.8)
Zhou           300.0           0.8           -         RT-PCR
et al. (25)   (234.0-407.0)   (0.4-3.2)
Chen          -               -              -         RT-PCR
et al. (26)
Chen           172.8          -               37.0     RT-PCR
et al. (27)   (142.6-220.5)                  (21.0-
                                              62.0)
Chen           321.5           1.1            32.5     RT-PCR
et al. (28)   (249.8-510.5)   (0.5-3.2)      (17.3-
                                              53.8)
Chen           336.0           0.9            49.9     RT-PCR
et al. (29)   (260.0-447.0)   (0.5-2.8)
Ai             245.4          _               33.3     RT-PCR and
et al. (30)                                            CT-scan
Xu             296.4           2.7           -         RT-PCR
et al. (31)                   (0.1-382.0)
Zhang         -               -              -         RT-PCR and
et al. (32)                                            abnormal
                                                       radiologic
                                                       findings
Zhao           233.0          -               30.1     RT-PCR
et al. (5)    (176.5-313.0)                  (11.5-
                                              69.0)
Zhao          -               -               -        RT-PCR
et al. (33)
Tian          -               -                        RT-PCR
et al. (34)
Wang           301.0           1.2           -         RT-PCR
et al. (35)   (224.0-429.0)   (0.6-3.2)
Wang           396.5           1.3           _         RT-PCR
et al. (3S)   (357.6-529.0)   (6.7-4.7)
Huang          502.5           8.6           -         RT-PCR
et al. (37)   (410.0-629.0)   (2.4-20.0)
Zhang          515.0           5.1           -         RT-PCR
et al. (38)   (365.0-755.0)   (2.2-21.5)
Zhang         -                0.2           -         RT-PCR
et al. (39)                   (0.1-0.5)
Zhang          262.9          -              -         RT-PCR
et al. (40)   (168.5-508.0)
Zhao           256.9          -              -         RT-PCR
et al. (41)   (150.0-750.0)
Tang           483.0           0.6           -         Clinical
et al. (42)   (351.0-602.0)   (0.4-3.4)                presentations,
                                                       CT-scan
Tang          -               -              -         RT-PCR
et al. (43)
Liao           195.5           0.3           -         RT-PCR assay
et al. (44)   (145.0-240.0)   (0.2-0.4)                with a cycle
                                                       threshold value
                                                       (Ct-value) of
                                                       less than 37
                                                       was defined as
                                                       positive
Qian          -                0.3           -         Real-time
et al. (45)                   (0.1-0.4)                reverse
                                                       transcriptase
                                                       as a primary
                                                       method of
                                                       diagnosis,
                                                       RT-PCR
Qiu           -                0.5           -         RT-PCR
et al. (46)                   (0.2-0.7)
Shi           -               -              -         NA (Medical
et al. (47)                                            records)
Wan            320.5           0.4           -         RT-PCR
et al. (48)   (248.5-385.3)   (0.2-0.6)
Xu            -               -              -         RT-PCR
et al. (49)
Wu             226.0           0.9                     Epidemiological
et al. (50)   (182.0-308.0)   (0.4-2.4)                history, clinical
                                                       manifestations,
                                                       RT-PCR
Xie           -                0.7            39.0     RT-PCR, clinical
et al. (51)                   (0.3-1.3)      (24.0-    data
                                              58.0)
Xu             338.0          -              -         All patients
et al. (52)   (248.0-437.9)                            had positive
                                                       throat swabs of
                                                       SARS-CoV-2
Zhou           300.0           0.8           -         Real-time
et al. (25)   (234.0-407.0)   (0.4-3.2)                RT-PCR
Zhou           266.2           2.3           -         RT-PCR,
et al. (53)                                            CT-scan
Cai           -               -              -         RT-PCR
et al. (54)
Feng           259.0           0.58           48.0     Real-time
et al. (17)   (202.0-356.0)   (0.35-1.48)    (30.0-    RT-PCR,
                                                       80.0)
Feng           189.0          _              _         RT-PCR assay
et al. (55)   (152.0-244.0)                            for nasal and
                                                       pharyngeal
                                                       swab
                                                       specimens,
                                                       CT-scan
Fu            -               -              -         RT-PCR,
et al. (18)                                            CT-scan
Ji             234.0           0.3           -         RT-PCR
et al. (56)   (200.0-283.0)   (0.2-0.5)
Han           -               -              -         NA
et al. (57)
Jiang China   -                0.3           -         RT-PCR
et al. (58)                   (0.2-0.6)
Yang China                    -              -         RT-PCR
et al. (59)
Author          Clinical          Q/A
                stage of liver    score
                enzymes data
Huang           On admission      8
et al. (2)
Guan            On admission      8
et al. (23)
Fu              On admission      7
et al. (24)
Zhou            On admission      8
et al. (25)
Chen            On admission      5
et al. (26)
Chen            On admission      8
et al. (27)
Chen            On admission      8
et al. (28)
Chen            On admission      8
et al. (29)
Ai              On admission      8
et al. (30)
Xu              On admission      8
et al. (31)
Zhang           During            8
et al. (32)     admission
Zhao            On admission      7
et al. (5)
Zhao            On admission      8
et al. (33)
Tian            During            7
et al. (34)     admission
Wang            On admission      8
et al. (35)
Wang            During            6
et al. (3S)     admission
Huang           On admission      5
et al. (37)
Zhang           During            6
et al. (38)     admission
Zhang           During            8
et al. (39)     admission
Zhang           Medical           6
et al. (40)     records, NA
Zhao            After admission   7
et al. (41)
Tang            On admission      7
et al. (42)
Tang            Medical           6
et al. (43)     records, NA
Liao            On admission      8
et al. (44)
Qian            On admission      9
et al. (45)
Qiu             NA                9
et al. (46)
Shi             On admission      7
et al. (47)
Wan             Medical           8
et al. (48)     records, NA
Xu              Pathology         5
et al. (49)     sample from
                the liver after
                death
Wu              Medical           8
et al. (50)     records, NA
Xie             On admission      8
et al. (51)
Xu              On admission      8
et al. (52)
Zhou            On admission      7
et al. (25)
                methods
Zhou            On admission      7
et al. (53)
Cai             On admission      8
et al. (54)
Feng            On admission      8
et al. (17)
                CT-scan
Feng            On admission      8
et al. (55)
Fu              NA                8
et al. (18)
Ji              On admission      8
et al. (56)
Han             On admission      7
et al. (57)
Jiang China     Medical           7
et al. (58)     records, NA
Yang China      Medical           8
et al. (59)     records, NA
CRP: C-reactive protein, ALT: Alanine aminotransferase, AST: Aspartate 
aminotransferase, LDH: Lactate dehydrogenase, ESR: Erythrocyte 
sedimentation rate, Q/A: Quality assessment, RT-PCR: Reverse 
transcription polymerase chain reaction, CT-scan: Computed tomography 
scan, C/S: Cross-sectional
Table 2: Quality assessment scores for the included cross-sectional 
studies
Author              Representativeness   Sample   Non-respondents
                    of the sample        size
Huang et al. (2)    +                    +        -
Guan et al. (23)    +                    +        -
Fu et al. (24)      -                    +        -
Zhou et al. (25)    +                    +        -
Chen et al. (26)    +                    +        -
Chen et al. (27)    +                    +        -
Chen et al. (28)    +                    +        -
Chen et al. (29)    +                    +        -
Ai et al. (30)      +                    +        -
Xu et al. (31)      +                    +        -
Zhang et al. (32)   +                    +        -
Zhao et al. (5)     -                    +        -
Zhao et al. (33)    +                    +        -
Tian et al. (34)    -                    +        -
Wang et al. (35)    -                    +        +
Wang et al. (36)    -                    +        +
Huang et al. (37)   -                    +        -
Zhang et al. (38)   -                    +        +
Zhang et al. (39)   +                    +        -
Zhang et al. (40)   +                    +        -
Zhao et al. (41)    +                    +        +
Tang et al. (42)    -                    +        -
Tang et al. (43)    -                    +        +
Liao et al. (44)    +                    +        -
Qian et al. (45)    +                    +        +
Qiu et al. (46)     +                    +        +
Shi et al. (47)     -                    +        -
Wan et al. (48)     -                    +        +
Xu et al. (49)      -                    +        -
Wu et al. (50)      +                    +        -
Xie et al. (51)     +                    +        -
Xu et al. (52)      +                    +        -
Zhou et al. (25)    -                    +        -
Zhou et al. (53)    -                    +        -
Cai et al. (54)     +                    +        -
Feng et al. (17)    +                    +        -
Feng et al. (55)    +                    +        -
Fu et al. (18)      +                    +        -
Ji et al. (56)      +                    +        -
Han et al. (57)     -                    +        -
Jiang et al. (58)   -                    +        -
Yang et al. (59)    -                    +        -
Author              Ascertainment     Comparability   Assessment
                    of the exposure                   of the
                                                      outcome
Huang et al. (2)    ++                ++              +
Guan et al. (23)    ++                ++              +
Fu et al. (24)      ++                ++              +
Zhou et al. (25)    ++                ++              +
Chen et al. (26)    ++                N/A             +
Chen et al. (27)    ++                ++              +
Chen et al. (28)    ++                ++              +
Chen et al. (29)    ++                ++              +
Ai et al. (30)      ++                ++              +
Xu et al. (31)      ++                ++              +
Zhang et al. (32)   ++                ++              +
Zhao et al. (5)     ++                ++              +
Zhao et al. (33)    ++                ++              +
Tian et al. (34)    ++                ++              +
Wang et al. (35)    ++                ++              +
Wang et al. (36)    ++                N/A             +
Huang et al. (37)   ++                N/A             +
Zhang et al. (38)   ++                N/A             +
Zhang et al. (39)   ++                ++              +
Zhang et al. (40)   ++                N/A             +
Zhao et al. (41)    ++                ++              +
Tang et al. (42)    ++                ++              +
Tang et al. (43)    ++                N/A             +
Liao et al. (44)    ++                ++              +
Qian et al. (45)    ++                ++              +
Qiu et al. (46)     ++                ++              +
Shi et al. (47)     ++                ++              +
Wan et al. (48)     ++                ++              +
Xu et al. (49)      ++                N/A             +
Wu et al. (50)      ++                ++              +
Xie et al. (51)     ++                ++              +
Xu et al. (52)      ++                ++              +
Zhou et al. (25)    ++                ++              +
Zhou et al. (53)    ++                ++              +
Cai et al. (54)     ++                ++              +
Feng et al. (17)    ++                ++              +
Feng et al. (55)    ++                ++              +
Fu et al. (18)      ++                ++              +
Ji et al. (56)      ++                ++              +
Han et al. (57)     ++                ++              +
Jiang et al. (58)   ++                ++              +
Yang et al. (59)    ++                ++              ++
Author              Statistical   Total
                    test
Huang et al. (2)    +             8
Guan et al. (23)    +             8
Fu et al. (24)      +             7
Zhou et al. (25)    +             8
Chen et al. (26)    +             6
Chen et al. (27)    +             8
Chen et al. (28)    +             8
Chen et al. (29)    +             8
Ai et al. (30)      +             8
Xu et al. (31)      +             8
Zhang et al. (32)   +             8
Zhao et al. (5)     +             7
Zhao et al. (33)    +             8
Tian et al. (34)    +             7
Wang et al. (35)    +             8
Wang et al. (36)    +             6
Huang et al. (37)   +             5
Zhang et al. (38)   +             6
Zhang et al. (39)   +             8
Zhang et al. (40)   +             6
Zhao et al. (41)    +             7
Tang et al. (42)    +             7
Tang et al. (43)    +             6
Liao et al. (44)    +             8
Qian et al. (45)    +             9
Qiu et al. (46)     +             9
Shi et al. (47)     +             7
Wan et al. (48)     +             8
Xu et al. (49)      +             5
Wu et al. (50)      +             8
Xie et al. (51)     +             8
Xu et al. (52)      +             8
Zhou et al. (25)    +             7
Zhou et al. (53)    +             7
Cai et al. (54)     +             8
Feng et al. (17)    +             8
Feng et al. (55)    +             8
Fu et al. (18)      +             8
Ji et al. (56)      +             8
Han et al. (57)     +             7
Jiang et al. (58)   +             7
Yang et al. (59)    +             8
N/A: Not applicable
Table 3: A summary of pooled results from the included articles
Variable            All patients
                    Number     I-             Prevalence   Number
                    of         squared        % (95% CI)   of
                    articles                               articles
Clinical outcomes
Discharged          23         99.88          55 (38-72)    8
Death               22         99.97          19 (1-37)    10
Hospitalization     15         99.85          80 (69-90)   -
ICU admission       22         99.93          25 (3-47)    -
Laboratory
findings
Increase in ALT     20         91.30          17 (13-21)   10
Increase in AST     19         92.59          18 (14-23)   11
Increase in total    8         90.69          12 (7-17)     4
bilirubin
Decrease in          6         99.87          44 (0-88)     3
albumin
Increase in         18         96.66          53 (43-62)   10
C-Reactive
Protein
Increase in LDH     18         98.23          36 (25-47)    9
Increase in ESR      9         91.90          57 (44-70)    -
Increase in         17         97.97          35 (24-47)    9
D-dimer
Complication
Liver toxicity      13         95.35          20 (14-26)    7
Variable            Severe
                    I-        Prevalence   Number
                    squared   % (95% CI)   of
                                           articles
Clinical outcomes
Discharged          98.52     32 (19-44)   4
Death               99.87     55 (45-66)   3
Hospitalization     -         -            -
ICU admission       -         -            -
Laboratory
findings
Increase in ALT     97.47     38 (18-58)   6
Increase in AST     94.03     48 (34-63)   8
Increase in total   66.67     17 (9-25)    2
bilirubin
Decrease in         -         36 (4-67)    -
albumin
Increase in         96.07     78 (69-88)   7
C-Reactive
Protein
Increase in LDH     97.36     75 (62-87)   4
Increase in ESR     -         -            -
Increase in         94.70     79 (70-89)   6
D-dimer
Complication
Liver toxicity      97.23     41 (19-62)   2
Variable            Non-severe
                    I-        Prevalence
                    squared   % (95% CI)
Clinical outcomes
Discharged          99.97     53 (-3-109)
Death               43.21      0 (0-1)
Hospitalization     -         -
ICU admission       -         -
Laboratory
findings
Increase in ALT     97.09     30 (16-44)
Increase in AST     90.79     21 (13-29)
Increase in total   -         10 (7-12)
bilirubin
Decrease in         -         -
albumin
Increase in         98.57     55 (36-73)
C-Reactive
Protein
Increase in LDH     71.85     39 (28-49)
Increase in ESR     -         -
Increase in         96.07     28 (14-41)
D-dimer
Complication
Liver toxicity      -         17 (13-20)
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Author:Zahedi, Mohammad; Yousefi, Mohammad; Abounoori, Mahdi; Malekan, Mohammad; Tajik, Fatemeh; Heydari, K
Publication:Iranian Journal of Medical Sciences
Geographic Code:7IRAN
Date:Jul 1, 2021
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