Acute pericarditis and renal failure complicating acute hepatitis A infection.

Abstract: Hepatitis A infection may result in acute hepatitis, and rarely, fulminant hepatitis may ensue. Extrahepatic manifestations of hepatitis A are uncommon. The authors present the case of a 77-year-old male who had development of acute renal failure and pericarditis during the clinical course of acute hepatitis A infection. He died as a result of septic shock on the fifth day of hospitalization. To the best of our knowledge, this is the first report of both these rare and serious complications appearing in the same patient.

Key Words: hepatitis A, extrahepatic complications, pericarditis, acute renal failure

Introduction

The clinical spectrum of acute hepatitis A virus (HAV) infection includes silent infection, subclinical infection detected by abnormal liver tests, clinically apparent hepatitis, and, rarely, fulminant hepatitis. (1) Although rare, reported cardiac manifestations include bradycardia, ECG changes (prolongation of PR interval and some mild T-wave depression) and pericarditis. (2) Furthermore, HAV infection is very rarely complicated by acute renal failure. (3-5) We report a patient with hepatitis A infection who presented with both acute pericarditis and acute renal failure.

Case Report

A 77-year-old nonalcoholic male was admitted to our hospital with a history of syncope, anorexia, nausea, and decreased urine output. He reported no foreign travel, use of drugs or alcoholic beverages, or blood transfusion. His history was otherwise unremarkable. On physical examination, the patient was ill and lethargic. His temperature was 36.8[degrees] C, blood pressure was 120/78 mm Hg, and his respiratory rate was 32/min. Chest auscultation revealed a pericardial friction rub with bilateral rales. He had mild diffuse abdominal tenderness but no ascites, hepatosplenomegaly, spider angiomas, or asterixis.

A blood workup at admission revealed a hemoglobin level of 12.5 g/dL, white blood cell count of 11,500/[mm.sup.3] with a normal differential count, and a platelet count of 178,000/[mm.sup.3]. Serum [Na.sup.+] and [K.sup.+] concentrations were 139 mEq/L and 5.0 mEq/L, respectively. On arterial blood gas analysis, blood pH was 7.3, with an HC[O.sub.3] level of 15.9 mEq/L. His blood glucose was 147 mg/dL; serum alanine transaminase, 1,877 U/L; serum aspartate transaminase, 2,612 U/L; alkaline phosphatase, 125 U/L; [gamma]-glutamyl transferase, 113 U/L; total bilirubin, 1.74 mg/dL; blood urea nitrogen, 28.2 mg/dL; and creatinine, 1.5 mg/dL. Serum osmolality was 306, and his international normalized ratio was 2.27. The erythrocyte sedimentation rate was 15 mm/h. Serum antinuclear antibody, antibodies to extranuclear antigens, and rheumatoid factor were not detected. Thyroid hormone levels were within normal range. A toxicology screen was negative for acetaminophen, salicylate, and ethanol. Urinalysis showed yellow urine with a specific gravity of 1.025, pH of 5.0, and protein concentration of 100 mg/dL, with no detectable bilirubin. Urinary sediment contained 2 to 3 white blood cells per high-power field and 4 to 5 red blood cells per high-power field, with sparse hemoglobin and granular casts.

Chest radiography revealed an increased cardiothoracic index and minimal pleural effusion. The liver was normal in appearance on abdominal ultrasonography, with the absence of gallbladder stones and a nondilated biliary tract. Kidneys were reduced in size, with normal parenchymal echogenicity, and there was no apparent dilation of the urinary tract. Echocardiography (Fig.) revealed an ejection fraction of 51%, along with pericardial effusion causing mild atrial collapse.

Oliguria developed in this patient 24 hours after admission. On the second day of admission, the patient became anuric, despite appropriate intravenous hydration and diuretic therapy. Pericardiocentesis and renal biopsy could not be performed because of the bleeding tendency. The serum blood urea nitrogen, creatinine, and [K.sup.+] levels increased to 55 mg/dL, 4.0 mg/dL, and 5.5 mEq/L, respectively. The blood pH decreased to 6.93. At this point, hemodialysis was initiated. The results of serologic studies showed positive IgM anti-HAV antibodies (repeated twice), whereas anti-HAV IgG and serologic tests for hepatitis B and C, cytomegalovirus, and Epstein-Barr virus were all negative.

On subsequent laboratory examination, there was minimal improvement in transaminase and bilirubin levels. On the fourth day of admission, the patient had a high fever and hypotension. Blood and urine cultures were obtained, and broad-spectrum antibiotics were administered because community-acquired sepsis could not be excluded. He died as a result of Escherichia coli sepsis on the fifth day after admission.

Discussion

The differential diagnosis for serum alanine transaminase and serum aspartate transaminase levels in the thousands includes a very short list of drugs, exposure to hepatotoxins such as carbon tetrachloride, and viral hepatitis. Of these possibilities, the diagnosis of HAV infection was made in our patient on the basis of positive anti-HAV IgM serology. Acute hepatitis A is a common viral infection found throughout the world. Since immunity to hepatitis A (positive anti-HAV IgG) approaches 100% in adults in Turkey, hepatitis A infection is not usually considered in the initial differential diagnosis. (6)

The clinical manifestation of hepatitis A infection varies widely. Recognized complications of hepatitis A include cholestasis, prolonged and relapsing disease, fulminant hepatitis, triggering of chronic active autoimmune hepatitis, and autoimmune extrahepatic disease. (2) To the best of our knowledge, only two cases with cardiac complications of hepatitis A have been described in the literature, and neither patient died. The first case report describes a cardiac complication with myopericarditis and ventricular tachycardia. (7) The second was a 50-year-old female with myopericarditis reported by Bosson et al. (8) Although HAV replication in cells of extrahepatic origin has been documented in various cell lines and in several animal models, the precise pathophysiology of atypical manifestations has not been elucidated. It has been suggested that immune mechanisms may be involved. (9,10) Circulating immune complexes containing HAV and specific IgM antibodies have been found during infection. (2) Acute pericarditis may occur during the clinical course of uremia; however, pericardial effusion was diagnosed while renal function tests were within normal limits in our patient.

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Acute renal failure is a rare complication of hepatitis A infection. The exact mechanism by which the hepatitis A virus causes renal damage is still obscure. (3) Several possible mechanisms have been put forward. First, prerenal factors such as vomiting or diarrhea may cause circulatory insufficiency, which may then activate the renin-angiotensin system and impair renal blood flow. This may lead to tubular necrosis. This is supported by low urinary sodium concentration. (11) In our case, prerenal failure caused by fluid depletion was ruled out by the presence of a high urine sodium concentration. Second, hyperbilirubinemia may decrease effective blood volume by reducing total peripheral vascular resistance. (12) In contrast, hyperbilirubinemia may sensitize renal vasculature to circulating vasoconstricting stimuli resulting in vasoconstriction. (13) The combined effect may lead to redistribution of cardiac output away from the kidney. The patient's total bilirubin levels were mildly elevated, suggesting that the bilirubin effect only had a minor role in the development of acute renal failure. Third, glomerulonephritis secondary to the deposition of HAV-associated immune complexes is a proposed mechanism. (14) Garel et al (15) reported two cases of mesangial IgM glomerulonephritis associated with hepatitis A, and Ilan and Galun (16) reported a patient with acute hepatitis A infection and presumed glomerulonephritis based on proteinuria, red blood cell casts, and microscopic hematuria, in the absence of any other etiologic agent(s). In our case, the presence of proteinuria, red cell casts in the urine sediment, and high urine sodium concentration suggest glomerulonephritis, but a kidney biopsy could not be performed because of impaired coagulation parameters.

Reported deaths during the course of hepatitis A infection are mostly related to fulminant hepatitis. Unless it is fulminant, death is unusual and most often accompanied with acute renal failure complicated by septicemia. (3)

Conclusion

With unclarified mechanisms, acute HAV infection may cause renal failure and acute pericarditis. Therefore, physicians must be aware of the potential extrahepatic complications of hepatitis A infection. We suggest that cardiac examination and renal function monitoring should be done during the evaluation of hepatitis A--infected patients. Moreover, to understand the underlying pathophysiological mechanisms of extrahepatic complications, histopathological examinations done on medically available patients are needed.

References

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3. Wilkinson SP, Davies MH, Portmann B, et al. Renal failure in otherwise uncomplicated acute viral hepatitis. Br Med J 1978;2:338-341.

4. Conrad ME, Schwartz FD, Young MA. Infectious hepatitis: A generalized disease. Am J Med Sci 1964;37:789-801.

5. Vesely DL, Dilley RW, Duckworth WC, et al. Hepatitis A-induced diabetes mellitus, acute renal failure, and liver failure. Am J Med Sci 1999;317:419-424.

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7. Sthoeger ZM, Ayzenberg O, Caspi A. Ventricular tachycardia associated with acute hepatitis A infection. Eur J Med 1993;2:248-249.

8. Bosson C, Lim DQ, HadramiJ, et al. Myopericarditis during hepatitis A. Presse Med 1996;25:995-996.

9. Lemon SM. Type A viral hepatitis. N Engl J Med 1985;313:1059-1067.

10. Green J, Beyar R, Bomzon L, et al. Jaundice, the circulation and the kidney. Nephron 1984;37:145-152.

11. Takeshita S, Yamakado M, Nagano M, et al. A case of sporadic acute type A hepatitis associated with acute renal failure. Nippon Jinzo Gakkai Shi 1994;36:871-875.

12. Green J, Better OS. Systemic hypotension and renal failure in obstructive jaundice-mechanistic and therapeutic aspects. J Am Soc Nephrol 1995;5:1853-1871.

13. Kawai K, Tomita E, Suginara J, et al. A case of acute hepatitis type A with acute renal failure: report of a case with renal biopsy. Nippon Shokakibyo Gakkai Zasshi 1983;80:1345-1348.

14. Zikos D, Grewal KS, Craig K, et al. Nephrotic syndrome and acute renal failure associated with hepatitis A virus infection. Am J Gasteroenterol 1995;90:295-298.

15. Garel D, Vasmant D, Mougenot B, et al. Glomerular nephropathy with mesangial proliferation and acute hepatitis A virus infection: Two cases. Ann Pediatr (Paris) 1986;33:185-188.

16. Ilan Y, Galun E. Glomerulonephritis associated with acute HAV infection. J Clin Gastroenterol 1992;15:85.</p> <pre> A fool thinks himself to be wise, but a wise man knows himself to be a fool. --William Shakespeare </pre> <p>Yavuz Beyazit, MD, Gulay Sain Guven, MD, Murat Kekilli, MD, Seyfettin Koklu, MD, Omer Faruk Yolcu, MD, and Ali Shorbagi, MD

From the Faculty of Medicine, Department of Internal Medicine, Hacettepe University, Ankara, Turkey, and the Department of Gastroenterology, Yuksek Ihtisas Hastanesi, Ankara, Turkey.

Reprint requests to Dr. Gulay Sain Guven, Hacettepe University Faculty of Medicine, Department of Internal Medicine, Sihhiye, 06100, Ankara, Turkey. E-mail: [e-mail]

Accepted September 9, 2005.

RELATED ARTICLE: Key Points

* Hepatitis A is usually a self-limited infection of the liver but can result in a fatal infection with extrahepatic complications.

* Extrahepatic complications of hepatitis A include acalculous cholecystitis, hemolysis, and reactive arthritis.

* Although rare, acute renal failure and acute pericarditis may develop during the course of type A hepatitis infection.