Acute Hepatitis E Virus Infection Presenting as a Prolonged Cholestatic Jaundice Laura Mechnik, M.D., Nina Bergman, M.D., Malka Attali, M.D., Marc Beergabel, M.D., Bruce Mosenkis, M.D., Nadia Sokolowski, M.D., and Stephen Malnick, M.A.(Oxon), M.Sc., M.B.B.S. Abstract Hepatitis E virus (HEV) is an enteric virus that usually causes a self-resolving hepatitis; although, it may be fatal, especially in pregnant women. Although HEV is endemic in Israel, there have been no recent local outbreaks. We report the case of a 70-year-old man who presented with painless jaundice. Ultrasound and ab- dominal computed tomography scan revealed gallstones, with no evidence of cholecystitis and no dilatation of the intra- or extra- hepatic bile ducts. An open cholecystectomy was performed with intraoperative cholangiography. There was no evidence of choled- ocholithiasis. A subsequent endoscopic retrograde cholangiopan- creatography was normal. His bilirubin level subsequently increased to a maximum of 25 mg/dL, and his gamma-glutamyl- transferase level reached 1,400 U/L. There was no evidence of any autoimmune or metabolic disease, and routine viral serology was normal except for immunoglobulin G to hepatitis A virus. A liver biopsy revealed an acute cholestatic picture. The jaundice resolved slowly after a period of 6 months. Hepatitis E virus RNA was isolated from the acute-phase serum and was not de- tectable in the convalescent serum. This case is a unique example of chronic cholestatic jaundice that we think is caused by acute HEV infection. Key Words: Hepatitis E virus—Cholestatic jaundice—Prolonged. H epatitis E virus (HEV) is an enteric virus that causes an acute hepatitis. 1 Although it may be fatal, especially in pregnant women, 2 the course is usually benign and self- resolving. We recently treated a patient with a prolonged cholestatic jaundice that we believe was caused by HEV. This is an extremely rare, if not unique, presentation of this hepatitis virus. CASE REPORT A 70-year-old man, born in the former USSR who immigrated to Israel 5 years previously, was hospitalized because of the ap- pearance of increasing jaundice. Two weeks before, he experi- enced right upper quadrant abdominal pain, nausea, and lassitude. Subsequently, he developed pruritus, acholic stools, and dark urine. His previous medical history included a partial gastrectomy 9 years previously for a peptic ulcer. He was taking no regular medication and did not report alcohol use. Physical examination revealed an icteric man, in otherwise good health, with no signs of hepatic failure. A central abdominal scar was evident. The gallbladder was not palpable and neither were the liver or spleen. No Kaiser–Fleischer rings were detect- able. An ultrasound was performed that revealed the presence of gallstones but no evidence of cholecystitis. A computed tomogra- phy of the abdomen confirmed the presence of gallstones, but no dilatation of the bile ducts was seen. Laboratory investigations revealed a bilirubin level of 4.5 mg/dL; aspartate aminotransferase, 175 U/L; alanine aminotransferase, 318 U/L; and alkaline phos- phatase, 318 U/L. Also, his gamma-glutamyl-transferase level was elevated to 1,400 U/L. The hepatitis A virus (HAV), hepatitis B virus, and HCV antibodies were negative except for immunoglob- ulin G (IgG) anti-HAV. In addition, both cytomegalovirus and Epstein–Barr virus antibodies were IgG-positive. Antinuclear an- tibodies, anti–smooth muscle antibodies, antimitochondrial anti- bodies, and anti–liver kidney microsomal antibodies were negative. His serum ceruloplasmin level was 35 mg/dL, and his bilirubin level progressively increased over the course of several days to 20.6 mg/dL. Serum ferritin and urinary copper excretion were within normal limits. An open cholecystectomy with an in- traoperative cholangiogram was performed that revealed a gall- bladder containing multiple small stones and no evidence of choledocholithiasis. The postoperative course was complicated by the increasing severity of the jaundice and bilirubin levels in- creased to 25 mg/dL. An endoscopic ultrasound was unsuccessful in visualizing the biliary system because of the previous partial gastrectomy. Because of this, an endoscopic retrograde cholangio- pancreatography was performed, which revealed a normal biliary and pancreatic duct system. A liver needle biopsy revealed chole- stasis with bile plugs in the canaliculi, feathery degeneration of hepatocytes, and liver cell rosettes. In addition, lobular inflamma- tion and fatty changes of the hepatocytes were seen (Fig. 1). This was consistent with an acute cholestatic lesion, most likely of viral origin. A trial of oral steroids (prednisone 40 mg once daily) was started, but the patient reported feeling distinctly worse, and the treatment was stopped after 5 days. Over the course of 6 months, the jaundice slowly resolved together with the other disturbances in the liver enzymes, and the patient remained in good health 1 year later. Hepatitis E virus RNA was detected by polymerase chain reaction in the acute serum but not in the convalescent serum. This test was performed in the National Reference Laboratory with the appropriate positive and negative controls. Hepatitis E virus antibody testing is not avail- able in Israel. On follow-up, the patient recalled eating raw shell- fish 2 weeks before the start of his illness. DISCUSSION We report a case of prolonged cholestatic jaundice that resolved during a period of 6 months. We believe that this a unique manifestation of acute HEV infection. There was a prodrome that was consistent with a viral infection. Serum transaminase levels were elevated to approximately five times the upper limit of normal but were first checked after Submitted September 22, 2000.Accepted February 28, 2001. From the Division of Internal Medicine, Kaplan Medical Center, Re- hovot, Israel. Address correspondence to Dr. Stephen Malnick, Department of Inter- nal Medicine C, Kaplan Medical Center, Rehovot 76100, Israel. E-mail: stevash@trendline.co.il J Clin Gastroenterol 2001;33(5):421–422. © 2001 Lippincott Williams & Wilkins, Inc. 421