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PREVALENCE OF DIFFERENT SONOGRAPHIC STAGES AMONG NEWLY DIAGNOSED CASES OF CHRONIC HEPATITIS C.

Byline: Hidayat Ullah, Atiq Ur Rehman and Ayesha Zafar

Abstract

Objective: To find the prevalence of different sonographic stages among newly diagnosed cases of chronic hepatitis C.

Study Design: Cross sectional study.

Places and Duration of Study: Armed Forces Institute of Radiology and Imaging Rawalpindi, from June 2014 to December 2015.

Material and Methods: All freshly diagnosed patients of chronic hepatitis C (CHC) with a positive anti-HCV and a positive PCR for HCV were subjected to ultrasound abdomen. The sonographic stage of CHC was decided as per previously defined criteria. Prevalence of each sonographic stage at the time of initial diagnosis was determined. Study population was divided in two groups of 'Early stage CHC' (sonographic stage I, II) and 'Advanced stage CHC' (sonographic stage III, IV, V). Student's t-test was applied to compare the means of the values for different sonographic parameters in the two groups.

Results: The study included 178 patients with male to female ratio of 1.86:1. Mean age was 47.5 +- 12.5 years. Prevalence of sonographic stages I, II, III, IV, Va and Vb in study population was 68% (n=121), 12% (n=21), 9% (n=16), 6% (n=11), 3% (n=5) and 2% (n=4) respectively. 'Early stage CHC' and 'advanced stage CHC' showed statistically significant (p-value <0.01) difference between average values of liver size, portal vein caliber, mean portal vein velocity and splenic size.

Conclusion: The prevalence of advanced stage CLD (stage III-V) among newly diagnosed cases of chronic hepatitis C is as high as 20% despite the availability of diagnostic facilities.

Keywords: Cirrhosis, End stage liver disease, Hepatitis C, Hepatitis C antibodies, Ultrasonongraphy.

INTRODUCTION

Hepatitis C Virus (HCV) infection is present all across the globe. It has been an important cause of hepatitis following blood transfusion in the United States and Europe until anti-HCV screening of blood donors was introduced in 19911. According to World Health Organization, HCV infection is present in approximately 3% of the world population where about 170 million people having chronic hepatitis C (CHC) are at risk of eventually having hepatic cirrhosis and/or hepatocellular carcinoma2-4.

Sievert et al found that countries with high rates of CHC are Egypt (15% of population), Pakistan (4.7% of population) and Taiwan (4.4 % of population)5. A local study however suggested a prevalence of 6% in Pakistan where about ten million people were found to be the carriers of this infection6. Keeping in view the alarming prevalence of HCV infection in Pakistan, there is a need of awareness both among doctors and general population so that affected cases are diagnosed early and treatment instituted accordingly.

Screening people for anti-HCV antibodies provides an efficient way of diagnosing HCV infection. Positive cases can then undergo a polymerase chain reaction (PCR) test for HCV to confirm the activity of the disease. Liver sonography also provides an easy, readily available and cost effective imaging modality for diagnosing the well established cases and assessing the progress of CHC7. Findings on abdominal sonography can also be conveniently used to formulate a sonographic staging system of the disease which can help us decide if the disease has been diagnosed early or late.

Table-I: Average liver size, portal vein caliber, mean portal vein velocity and splenic size in different sonographic stages of CHC.

Sonographic stage###Liver size (cm)###Portal vein caliber###Mean Portal Vein###Spleen size

of CHC###Mean +- SD###(mm)###Velocity (cm/sec)###(cm)

###Mean +- SD###Mean +- SD###Mean +- SD

Stage I###13.9 +- 0.6###10.7 +- 0.9###19.7 +- 2.7###10.4 +- 0.6

Stage II###13.6 +- 0.5###11.8 +- 0.8###19.5 +- 2.7###12.2 +- 0.9

Stage III###12.4 +- 0.9###13.8 +- 0.5###11.6 +- 1.3###14.4 +- 0.8

Stage IV###10.3 +- 0.7###14.5 +- 0.6###9.5 +- 1.2###16.8 +- 1.2

Stage Va###11.1 +- 0.8###14.54 +- 0.4###11.2 +- 0.8###16.5 +- 0.5

Stage Vb###10.3 +- 0.3###14.4 +- 0.4###10 +- 0.8###17.3 +- 0.9

Table-II: Comparison of means of average liver size, portal vein caliber, mean portal vein velocity and splenic size in 'early stage CHC' and 'advanced stage CHC'. Values with different small letters are significantly (p<0.01) different from each other.

Sonographic Stage of CHC###Average Liver###Average PV###Average Mean PV###Average Spleen

###Size (cm)###Caliber (mm)###Velocity (cm/sec)###Size (cm)

Early stage CHC###13.9 +- 0.6a###10.9 +- 0.9b###19.7 +- 2.7a###10.7 +- 0.9b

(sonographic stage I, II)

Advanced stage CHC###11.3 +- 1.3b###14.2 +- 0.6a###10.7 +- 1.5b###15.7 +- 1.5a

(sonographic stage III, IV, V)

t-value###17.77###20.28###29.09###25.35

p-value###<0.01###<0.01###<0.01###<0.01

This study aimed to find the sonographic stage of CHC at the time of its initial diagnosis and use this information as an insight in to the awareness about the disease among doctors and general population.

The rationale of the study to find the prevalence of different sonographic stages among newly diagnosed cases of chronic hepatitis C.

PATIENTS AND METHODS

In this cross sectional study, patients were included by a non probability purposive sampling method. Patients of all ages and either gender reporting to Armed Forces Institute of Radiology and Imaging (AFIRI), Rawalpindi for ultrasound abdomen after having a positive anti-HCV test and a positive polymerase chain reaction (PCR) for HCV were included in the study. Previously undiagnosed cases having incidental findings suggestive of chronic liver disease (CLD) on abdominal sonography were also included if they were found reactive for anti-HCV with a positive PCR test. Already known cases of hepatitis C, patients with no or a negative PCR test, those with coexisting hepatitis B infection and unwilling patients were excluded. Normal hepatic parenchyma shows echogenicity equal to or a little greater than that of spleen and renal cortex8.

Liver has been described to have four sonographic grades with grade 0 depicting normal hepatic echogenicity while grade 1, 2 and 3 representing increasing fatty infiltration resulting in obscured margins of intrahepatic vasculature and the diaphragmatic outline9. Patients were excluded if they had grade 2 or more fatty infiltration of liver.

Sample size was calculated by using the following formula.

(Equation)

Where p=Prevalence of sonographically detectable CLD among study population expressed as a percentage; q=100-p; Za (Z Alpha)=1.96 using standard normal variate tables; and d (relative precision) = 20% of p10. A pilot study of 20 cases was carried out to find the approximate prevalence of sonographically detectable CLD among the study population.

This revealed 7 cases having sonographically detectable CLD at the time of initial diagnosis of HCV infection giving a value of 35% for p to calculate the minimum sample size of 178.

After an informed consent for inclusion in the study, ultrasound abdomen was carried out by a radiologist. All patients were scanned by the same radiologist using a 3.5 MHz convex transducer using Toshiba Nemio machine with Doppler facility. Same protocol was used for Doppler evaluation of portal vein to ensure standardization. Scanning was done during quite inspiration after overnight fasting. The probe was aligned along the long axis of the portal vein and measurement was made mid way between the formation of main portal vein and its bifurcation. The sample gate was kept open to include half to 2/3rd of the portal vein lumen with Doppler angle being always kept <60. Spectral analysis was done for 2-3 cycles and average of the mean portal vein velocity was recorded11.

Table-III: Sonographic staging of chronic liver disease.

Sonographic###Terminology###Sonographic findings

Stage of CLD

Stage I###No sonographic###Liver###Fine texture, smooth surface, sharp edge

###Chronic Liver

###Disease (NS-CLD)###Portal vein###Calibre <13mm, hepatopetal velocity 15 cm/sec

###Spleen###Size <12 cm, no splenic varices

###Ascites and/or###Nil

###pleural effusion

Stage II###Chronic Liver###Liver###Coarse texture, +- irregular surface, +- blunted edge

###Disease (CLD)

###Portal vein###Calibre 13mm, hepatopetal velocity 12 cm, +- splenic varices

###Ascites and/or###Nil

###pleural effusion

Stage IV###Decompensated###Liver###As in stage II

###Cirrhosis

###Portal vein###Calibre >13mm, hepatopetal velocity 12 cm, + splenic varices

###Ascites and/or###Present

###pleural effusion

Stage Va###Stage II/III with###Stage II/III with hepatic space occupying lesion suggestive of HCC

###HCC

Stage Vb###Stage IV with HCC###Stage IV with hepatic space occupying lesion suggestive of HCC

During ultrasonography following criteria were used to grade liver disease. Liver Grade 0 (Normal liver): Homogeneously fine echotexture, smooth surface; sharp edge; portal vein caliber <13 mm with hepatopetal velocity of [greater than or equal to]15 cm/sec12-14. Liver Grade 1 (chronic liver disease): coarse echotexture, +- irregular surface, +- blunt or rounded margin, portal vein caliber 13 mm and a hepatopetal velocity of <15 cm/sec or a hepatofugal flow. Liver Grade 3 (CLD with HCC): liver grade 1 or 2 with space occupying lesion/lesions suggestive of hepatocellular carcinoma. Spleen was graded as spleen grade 0: length 12 cm, no varices; spleen grade 2: length >12 cm with varices15. Note was made for presence of ascites and/or pleural effusion.

Based on these ultrasound findings, a sonographic stage of hepatitis C infection was decided as follows. Stage I: liver grade 0, spleen grade 0, no ascites or pleural effusion; Stage II: liver grade 1, spleen grade 0 or 1, no ascites or pleural effusion; Stage III: liver grade 2, splenic grade 1 or 2, no ascites or pleural effusion; Stage IV: liver grade 2, spleen grade 1 or 2, with ascites and/or pleural effusion; Stage Va: liver grade 3, spleen grade 1 or 2, no ascites and/or pleural effusion; Stage Vb: liver grade 3, splenic grade 1 or 2, with ascites and/or pleural effusion.

Findings were recorded on an already prepared proforma. Data were analyzed by SPSS 21. Prevalence of different sonographic stages of CHC among study population was calculated. Average liver size, portal vein caliber, mean portal vein velocity and splenic size were determined. Study population was divided in two groups of 'Early stage CHC' (sonographic stage I, II) and 'Advanced stage CHC' (sonographic stage III, IV, V). Student's t-test was applied to compare the means of the values for different sonographic parameters in the two groups16. A p-value of less than 0.05 was considered as significent value.

RESULTS

A total of 178 patients were included in the study. Out of them, 65% (n=116) were males while 35% (n=62) were females. Male to female ratio was 1.86:1. The mean age was 47.5 +- 12.5 years. The age distribution curve showed non-zero (positive) skewness (fig-1).

Stage I disease was found in 68% (n=121) while stage II disease was noted in 12% (n=21). Stage III disease was present in 9% (n=16) and stage IV CLD was detected in 6% (n=11) of patients. Stage Va was shown by 3% (n=5) and stage Vb was noted in 2% (n=4).

Table-I shows liver size, portal vein caliber, mean portal vein velocity and splenic size in different stages of hepatitis C with progressive change in the values of these variables as the disease advances in its sonographic stage. In 'Early stage CHC' the average liver size, average portal vein caliber, average mean portal vein velocity and average spleen size were 13.9 +- 0.6 cm, 10.9 +- 0.9 mm, 19.7 +- 2.7 cm/sec and 10.7 +- 0.9 cm respectively. In 'Advanced stage CHC', these values were 11.3 +- 1.3 cm, 14.2 +- 0.6 mm, 10.7 +- 1.5 cm/sec and 15.7 +- 1.5 cm respectively with statistically significant (p-value <0.01) difference between the two groups (table-II and fig-2).

DISCUSSION

Chronic hepatitis C is an important cause of morbidity and mortality all across the globe especially in the developing world. In Pakistan the overall prevalence of seropositivity for hepatitis C in general population is as high as 6% with about ten million people having HCV infection6. Some studies, however, suggest a lower prevalence of 3% in Pakistan which might be because of difference in the sample population17. Ultrasound plays an important role in the evaluation of such patients and detects the possible complications18.

There have been several models of classification and staging of CHC, some of which focus on the end stage liver disease for selecting patients for liver transplant19. Others focus on histopathological evaluation of hepatic inflammation and fibrosis for staging of the disease20,21. Our study introduced a staging model taking in to account the sonographic appearance of liver, portal vein and spleen along with the presence of ascites, pleural effusion and hepatocellular carcinoma. Ribeiro et al suggested a somewhat similar staging system but that was based on multimodal data22. The strength of the proposed staging model is coupling simple hepatic and splenic sonographic grades with other sonographic features making categorization of CLD possible. This sonographic staging model can be used for any chronic infection of liver including CHC and, if adopted by radiologists, is likely to make ultrasound reports in CLD patients more standardized and structured.

Table-III outlines the salient features of the sonographic staging model for CLD used in this study. Many cases of CHC go undetected till late because the disease is asymptomatic. Such cases are diagnosed only when the disease is complicated by portal hypertension, hepatic cirrhosis and hepatocellular carcinoma. Moorman et al in their chronic hepatitis Cohort Study (CHeCS) showed that 17% cases qualified for having a 'late diagnosis' despite having access to health care system23. Our study confirmed this finding in our set up where 20% cases presented in advanced stages of the disease (sonographic stage III, IV, V) at the time of initial diagnosis while 80% of cases were diagnosed in early stages (sonographic stage I, II). The high prevalence of 'late diagnosis' is alarming because it increases the morbidity and mortality associated with the disease.

A high index of suspicion is necessary for early diagnosis of infected patients/carriers to avoid complications and to reduce the spread of disease to others by timely institution of therapy. Introduction of mandatory blood screening test on annual basis especially in areas with high prevalence of HCV infected patients can be considered. This will help diagnosing majority of patients in NS-CLD stage of the disease who are more likely to be completely cured by the timely treatment.

Butterfield et al showed that in cases of severe mental illness, the rate of CHC infection in males was almost twice that among females24. This was attributed to their increased chances of exposure to the causative factors. In the multivariate model, however, gender was not found to be significantly playing a role in CHC. Our study, on the other hand, also showed that the proportion of seropositive males 65% (n=116) was almost twice the proportion of infected females 35% (n=62). The reasons are likely to be the same as outlined by Butterfield et al including more chances of being exposed to the causative factors. Alternatively less number of females reporting to the healthcare system because of socio economic reasons could also be playing some role. More, population based studies are required to find the representative epidemiologic features of CHC in Pakistan.

Advanced stage CHC has easily recognizable sonographic patterns. Smaller liver size with coarse echotexture, dilated portal vein with reduced mean velocity and occasionally even flow reversal, splenomegaly, the presence of ascites and/ or pleural effusion and presence of hepatic space occupying lesion in cases of hepatocellular carcinoma are the sonographic features which help in determining the stage of CLD. The study confirmed that there was a statistically significant (p-value <0.01) difference between 'Early stage CHC' and 'Advanced stage CHC' in terms of averege liver size, spleen size, portal vein caliber and portal vein folw velocity.

A limitation of this study is that it took into account only those seropositive cases who reported for ultrasound. Thus the sample might not be representative of the actual situation in general population. Larger population based studies are required to assess the situation more accurately and suggest appropriate steps for improvement.

CONCLUSION

Despite the availability of diagnostic facilities, the prevalence of advanced stage CLD (stage III-V) is as high as 20% among the newly diagnosed cases of chronic hepatitis C.

RECOMMENDATIONS

A high index of suspicion among the clinicians and periodic screening of general population can reduce this prevalence by ensuring an early diagnosis. The proposed sonographic staging, if adopted by radiologists, is likely to make ultrasound reports in CLD patients more standardized and structured.

CONFLICT OF INTEREST

This study has no conflict of interest to declare by any author.

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Publication:Pakistan Armed Forces Medical Journal
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Date:Apr 30, 2017
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