Clinical course of sporadic acute hepatitis E in a hepatitis B virus endemic region

Abstract

Objectives: In China, the epidemic pattern of acute hepatitis E virus (HEV) infection has changed from waterborne outbreaks to foodborne sporadic cases. However, the clinical course of sporadic acute hepatitis E (AHE) has not been well defined.

Methods: Consecutive patients with AHE who were admitted to the Jinan Infectious Disease Hospital, Jinan, Shandong Province between January 2003 and December 2014 were evaluated and followed. Demographic data, clinical manifestations, results of laboratory tests, and outcomes were recorded. Risk factors for liver failure and death were analyzed.

Results: A total of 680 patients with AHE were identified during the study period. The incidence was highest in February, March, and April, accounting for about 41% of the cases. The male to female ratio was 5.1:1 (574/106). The average age was 50.9±12.8years. The prevalence rates of prodromal fever, fatigue, loss of appetite, and jaundice were 25.6%, 85.6%, 83.8%, and 92.8%, respectively. The median (range) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and platelet levels were 727 (8-6270) U/l, 300 (17-6226) U/l, 196.8 (8.0-1083) μmol/l, 33.0 (15.2-45.8) g/l, and 162 (10-589)×10⁹/l, respectively. The prevalence of hepatitis B surface antigen (HBsAg) was 18.5% (126/680) and of liver cirrhosis was 9.4% (64/680). Thirteen percent (89/680) of the cases progressed to liver failure, including 4.1% (28/680) with acute liver failure (ALF) and 9.0% (61/680) with acute-on-chronic liver failure (ACLF). Among patients with HBsAg positivity or cirrhosis, 28.6% (36/126) and 36.0% (23/64), respectively, progressed to ACLF. Multiple logistic regression analysis indicated that age >53years, prodromal fever, HBsAg positivity, cirrhosis, and thrombocytopenia (platelet count <150×10⁹/l) were independently associated with the development of liver failure, with an odds ratio (95% confidence interval) of 2.5 (1.5-4.3), 1.9 (1.1-3.2), 3.7 (2.0-6.7), 2.1 (1.1-4.2), and 5.9 (3.3-10.4), respectively. The overall mortality was 5.6% (38/680), and the mortality rates in patients with and without underlying liver disease were 9.3% (22/237) and 3.6% (16/443), respectively. Multiple logistic regression analysis indicated that hepatic encephalopathy, bilirubin >500μmol/l, international normalized ratio (INR)>2, and severe thrombocytopenia (platelet count <100×10⁹/l) were independently associated with death, with an odds ratio (95% confidence interval) of 7.2 (2.4-21.8), 5.8 (1.9-17.2), 24.1 (7.9-73.3), and 10.8 (3.6-32.9), respectively.

Conclusions: In areas that are dual endemic for hepatitis B virus and HEV, the HEV vaccine for patients with obvious liver diseases is of significance. Thrombocytopenia is an important predictor of liver failure and mortality in sporadic AHE.

Keywords: Acute hepatitis E; Hepatitis B surface antigen; Liver cirrhosis; Liver failure; Platelets; Sporadic; Thrombocytopenia.