Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death

Background/Aims

India is hyper-endemic for hepatitis E virus (HEV). HEV infection in cirrhosis may cause high mortality. Prospective study evaluating HEV infection in cirrhotics is scarce.

Methods

Consecutive patients with cirrhosis and healthy controls were included. Cirrhotics were categorized to 3 groups, (Group I – rapid decompensation, Group II – chronically decompensated, Group III – cirrhotics without decompensation). Sera from cirrhotics and controls were tested for HEV-RNA (RT-PCR). HEV-RNA positivity among cirrhotics and controls was compared. Natural course and mortality rate between HEV infected and non-infected cirrhotics were assessed during a 12-month follow-up.

Results

107 cirrhotics and 200 controls were included. 30 (28%) cirrhotics and 9 (4.5%) controls had detectable HEV-RNA (p < 0.001). HEV- RNA positivity among Group I (n = 42), II (n = 32) and III (n = 33) cirrhotics was 21 (50%), 6 (19%) and 3 (10%), respectively (p = 0.002). 70% (21/30) with HEV infection and 27% (21/77) without it had rapid decompensation (p = 0.001). Mortality between HEV infected and non-infected cirrhotics at 4 weeks (43% vs. 22%, p = 0.001) and 12 month (70% vs. 30%, p = 0.001) was different. Multivariate analysis identified HEV infection, Child-Pugh’s score, renal failure, and sepsis as independent factors for mortality.

Conclusions

In India, cirrhotics were prone to HEV infection, which was associated with rapid decompensation and death.

Introduction

Hepatitis E virus (HEV) and hepatitis A virus (HAV) are hyper-endemic in the Indian subcontinent, China, Central Asia and Africa [1], [2], [3], [4]. A recent editorial in New England Journal of Medicine reported, a seroprevalence of HEV among 20% of blood donors in USA, identification of Swine HEV in USA and evidence of HEV epidemic in Japan [5]. HEV infection has also been documented in Australia and European Union [2], [6], [7], [8].

In hyper-endemic countries like India, sub-clinical HAV infection in childhood causes acquirement of protective anti-HAV antibody in almost all by the age of 16 years [9], [10]. In contrast, the prevalence of IgG anti-HEV antibody among adults in these region varies from 17.5% to 56% [11], [12], [13]. Protective role of IgG-anti-HEV is unclear and repeated HEV infection in an individual have been documented [14], [15]. Therefore, in hyper-endemic areas of HAV and HEV, while large immune population against HAV exist, the adult population remain susceptible to HEV infection, as documented during multiple epidemics of HEV in Asia and Africa [1], [2].

HAV and HEV infection in healthy individuals are associated with a mortality rate of 0.04–4% [1], [2]. However, in non-endemic area with non-immune population, HAV infection in patients with pre-existing chronic liver disease have been reported to cause death in 40% of such cases [16]. Therefore, HAV vaccination is recommended for patients with chronic liver disease [17]. Recently, few case series from Pakistan and India indicate that, HEV infection in pre-existing chronic liver disease may be associated with rapid decompensation and higher mortality [11], [13], [18]. In Indian subcontinent, 97–100% of patients with cirrhosis of liver are immune to HAV infection [9], [19], whereas, adult population with cirrhosis may be prone to contract HEV infection. Prospective study, defining the frequency of HEV infection among patients with cirrhosis, and its subsequent natural course has not been evaluated. The present prospective study was conducted, to identify whether patients with cirrhosis of liver are at high risk to contract HEV infection and whether HEV infection in them alters the natural course of the disease.