Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false‐positive antibodies

Abstract

Background and aims Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti‐HEV IgM and IgG, and HEV‐RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti‐HEV serology. Methods One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non‐AIH). Results Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non‐AIH). Patients with acute AIH and positive anti‐HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti‐HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). Conclusion Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross‐reactivity between HEV and liver antigens.

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection

“…In line with these data, the presence of autoantibodies has also been associated with HEV infection. This was very much like other forms of viral hepatitis [13,30,33,35,36]. However, it has not yet been clarified whether cryoglobulins or autoantibodies have a pathogenetic impact and contribute to overt disease in HEV-infected individuals.…”

“…The presence of autoantibodies has been described in HEV infection and in other viral diseases [ 11 , 12 , 13 ]. In contrast to true autoimmune diseases, there has been debate on the role of the immunological bystanders or the non-specific phenomena in HEV.…”

“…This suggested HEV as a possible trigger for the development of AIH, but a large Dutch cohort showed similar proportions of seropositive results in AIH patients compared with controls [ 16 ]. Whether or not the higher rate of seropositivity in AIH patients is merely due to false-positive testing because of higher levels of immunoglobulins has been debated [ 13 ]. In general, the presence of autoantibodies in sera from patients with active HEV infection is common [ 12 , 17 ].…”

Approach to the patient with acute severe autoimmune hepatitis

“…53 Cross-reactivity between HEV and liver autoantibodies raises the additional diagnostic dilemma of falsely positive HEV results. 53,54 There is increasing recognition that AIH is an important cause of ALF of unknown origin (potentially up to 62% of cases). 7,[55][56][57][58][59][60] Biopsy provides the opportunity to look for features of AIH, as well as to exclude other aetiologies (Fig.…”

“… 53 Cross-reactivity between HEV and liver autoantibodies raises the additional diagnostic dilemma of falsely positive HEV results. 53 , 54 …”