In cases of severe acute hepatitis E, liver failure, or immunosuppression of any cause, RBV treatment for three months
Most guidelines recommend treatment of RBV for three months in cases of severe acute hepatitis E, liver failure, or immunosuppression of any cause.4,5,7–9 However, there is a lack of high-quality randomized controlled experimental studies to support this recommendation. A multicenter retrospective study of 21 patients diagnosed with acute HEV infection (nine of whom had severe hepatitis and four were on immunosuppressive therapy) were treated with RBV at a dose of 600–800 mg/day for up to three months. All patients cleared HEV and returned to normal liver enzyme levels.22 Acute hepatitis E treatment has no specific drug other than RBV, although a case report describes successful treatment of severe hepatitis E with steroids, most guidelines do not recommend steroids for the treatment of acute hepatitis E due to insufficient evidence of efficacy.35
A survey conducted in Qujing, Yunnan Province, China, among pregnant women (n = 19,762) showed an HEV seropositivity rate of 11.6%, indicating a high prevalence of HEV among Chinese pregnant women.36 In Africa, the situation is not encouraging, with a pooled seroprevalence of 29.13% (95% confidence interval 14.63–43.63) among pregnant women.23 Patients infected with HEV during pregnancy may rapidly progress to acute liver failure, maternal mortality, and fetal death, especially in late pregnancy.37 The mechanism by which HEV infection in pregnant women leads to severe liver injury is unknown but may be related to elevated serum levels of oestradiol, which promotes hepatitis E virus replication.38
Challenges remain in the treatment of HEV infection in pregnant women. Currently, there is no established treatment for hepatitis E in pregnant women, which is symptomatic supportive care.39 Ribavirin is not recommended for pregnant women infected with HEV due to its teratogenic risk.40 However, in patients with acute HEV infection due to genotype 1 or 2, ribavirin treatment during the third trimester of pregnancy may be considered due to the high mortality of untreated HEV in mothers and vertically infected infants.7 A Chinese vaccine has shown protection against hepatitis E in the general population and appears to be safe during pregnancy, although its safety and efficacy in many pregnant women remain to be determined.37
The initial detection of Orthohepevirus C (HEV-C) occurred in rats from Germany and Vietnam.41 HEVs isolated from rats, the natural host of HEVs, are classified as HEV-C, while HEVs infecting humans are classified as Orthohepevirus A. RHEV and HEV-A are two highly divergent viruses, their genomes only share 50–60% genomic identity.42 Studies considered HEV-C incapable of infecting humans due to significant differences. However, the first case of human infection by rat HEV was reported in Hong Kong, with a second case reported in Canada.43,44 Asia is the continent with the highest incidence of infected animals, accounting for a total of 295 documented instances. China has the highest number of reported cases within the Asian region.45 Currently, studies utilized enzyme immunoassay methods for the antigenic diagnosis of rat type r-1 HEV and type b HEV.46 The most reliable method to determine orthohepevirus C infection is to detect viral genomic RNA by RT-PCR, including nested broad-spectrum RT-PCR.46,47 The first case of human infection by rat HEV was detected by RT-PCR in serum, feces, saliva, and liver tissue in human infection, and feces contained the highest RNA load.43 This discovery has significant implications for the epidemiology, clinical aspects, laboratory diagnosis, and prevention of HEV infection in humans.41