Acute renal failure associated with nonfulminant acute viral hepatitis A

Hepatitis A runs a benign course in children, but may have atypical presentations in adults. Very rarely acute renal failure complicates nonfulminant hepatitis A. We report a patient with nonfulminant acute viral hepatitis A with multiorgan involvement. Patient had biopsy proven acute interstitial nephritis, acute pancreatitis, acute myocarditis and required hemodialysis for 6 weeks.

For the next 5 weeks, he remained stable with gradually improving liver, cardiac, and pancreatic functions, but remained anuric requiring dialysis.Kidney biopsy was done after 6 weeks of onset of illness to know exact nature of renal involvement and for future prognostication.
Hepatitis A is usually a mild self-limiting infection of liver.Acute renal failure (ARF) complicating acute nonfulminant viral hepatitis A is exceedingly rare although it is not an uncommon association in cases of fulminant hepatitis with massive hepatic necrosis due to hepatitis A. 1 We are presenting here a case of a 25-year-old young male who developed ARF, acute pancreatitis, and myocarditis in the course of viral hepatitis A. The patient had prolonged ARF requiring dialysis.

Case Report
A 25-year-old young male, a resident of Assam, presented with history of fever, yellowish discoloration of sclera and urine, poor appetite, vomiting, pain upper abdomen, and decreased urine output for 1 week.He got admitted at a local hospital.Hospital summary showed that he was hemodynamically stable, had hepatomegaly, mild leucocytosis, deranged liver functions (AST 4404 U/L; ALT 4692 U/L; total/direct bilirubin 9.8/5.3mg/dl; prothrombin time (PT) (patient/control) 31/13 s; and deranged renal parameters (urea 154 mg/dl; creatinine 10.3 mg/dl; sodium 121 mg/dl; potassium 3.2 mg/ dl).He was initiated on hemodialysis.After 1 week, his liver functions started improving; however, he remained oligoanuric and uremic, and was subsequently referred to our hospital.At presentation, he had a BP of 170/90 mm Hg, tachycardia, tachypnoea, and low oxygen saturation.Examination revealed moderate pallor, Light microscopy [Figs. 1 and 2] showed normal glomeruli, patchy moderate mixed inflammatory cell interstitial infiltrate composed of lymphocytes, plasma cells, neutrophils, and a few eosinophils.Mild interstitial fibrosis was also present.The tubular epithelium showed flattening and desquamation in focal areas.Blood vessels appeared normal.Immunofluorescence was negative for IgA, IgG, IgM, C3, C1q, and fibrinogen.

Discussion
Typical presentations of viral hepatitis A include an asymptomatic form seen in young children under the age of 5 years and symptomatic form seen in relatively older children and adults, characterized by malaise, fatigue, and icteric hepatitis. 2Very rarely nonfulminant hepatitis A has lead to ARF. [3][4][5] When such a patient develops renal failure, common causes such as sepsis, shock, drug toxicity, bacterial infections, and rhabdomyolysis should be ruled out first.Although hepatitis A is usually a benign self-limited disease; however, in the present case it was associated with three unusual manifestations namely acute interstitial nephritis leading to prolonged oliguric ARF requiring dialysis, acute pancreatitis, and myocarditis.Patient had only acute hepatitis A infection as is confirmed by reactive hepatitis A IgM antibody.He required multiple sessions of hemodialysis for 6 weeks and gradually recovered normal hepatic and renal functions with normalization of pancreatic enzymes and myocarditis.The prognosis of the renal failure due to hepatitis A virus (HAV) infection is good, although the recovery was substantially delayed.Pancreatitis was diagnosed on the basis of characteristic epigastric pain radiating to back, a small sympathetic effusion, and very high pancreatic enzymes, which improved along with improvement of renal and liver functions.Myocarditis was also self-limiting, suspected on clinical grounds, and confirmed by Echo-Doppler.

Shroff et al. reported two cases of ARF associated with hepatitis A out of which one patient required dialysis.
They suggested beneficial role of high dose acetylcysteine in recovery of renal function. 3Vesely et al. related the peak bilirubin levels to the requirement of hemodialysis in patients who developed ARF in the setting of viral nephritis. 5There also seems to be temporal relationship between improvement of the bilirubin concentration and improvement in renal functions. 5,6ust and Pimstone reviewed the literature on ARF-associated with hepatitis A infection.Acute tubular necrosis (ATN) was the most common histopathological diagnosis.Acute interstitial nephritis, mesangial proliferative glomerulonephritis, and normal histology were also reported as single cases. 7Vaboe et al. described combination of interstitial nephritis and ATN associated nonfulminant hepatitis A requiring dialysis support. 8Also viral hepatitis A has been rarely associated with cardiac manifestations 9 and pancreatitis. 10We could not find any such case with combination of renal, cardiac, and pancreatic involvement associated with viral hepatitis A in the literature.Several mechanisms have been postulated in the pathogenesis of ATN in such settings; these include insufficient renal blood flow due to developing endotoxemia or due to direct cytopathic effect of the virus; while mesangial profilerative glomerulonephritis and interstitial nephritis are due to immune complexes or cryoglubulinemia.
Present case demonstrates that hepatitis A infection can be very severe, resulting in acute interstitial nephritis requiring prolonged dialysis support, myocarditis, and pancreatitis in an apparently healthy individual.Thus in the course of nonfulminant hepatitis A, renal functions should be closely monitored.