Lamivudine therapy in chronic delta hepatitis: a multicentre randomized‐controlled pilot study

Abstract

SUMMARYBackground: Delta virus (HDV)-related chronic hepatitis is difficult to treat. Aims: To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA, hepatitis D virus antibodies and alanine aminotransferase levels, liver histology, and on hepatitis B surface antigen seroconversion. Methods: Thirty-one hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT ‡ 1.5 upper normal level and compensated liver disease were randomized (1:2 ratio) to placebo (group A, n ¼ 11) or lamivudine (group B, n ¼ 20) for 52 weeks; thereafter, all patients were given lamivudine for 52 weeks and followed up for 16 weeks.

Mathematical models of the interrelated dynamics of hepatitis D and B

“…One would expect that administering lamivudine to individuals with chronic HBV and HDV would also reduce HDV levels. However, studies have shown that administering lamivudine has no significant effect on the levels of HDV RNA in infected patients [9,11,23,10]. Even after months of treatment, HDV viral production and liver damage (i.e.…”

“…infection) remain high. Furthermore, HBV levels can return post treatment [9,11]. It is believed that lamivudine inhibits HBV replication downstream of RNA production, which allows for continued production of HBsAg [9].…”

“…Additional compartments are needed for free HBV and HDV particles. In this paper, we develop a basic model for the interaction of HBV and HDV infection, conduct an analysis of its steady state structure and stability, and test model behavior against experimental results from drug treatment trials [9][10][11].…”

Diagnosis, management and treatment of hepatitis delta virus infection: Turkey 2017 Clinical Practice Guidelines

“…The combination treatments performed so far have not been shown as more effective than interferon treatment alone (39,(41)(42)(43)(44)46). However, with new treatments currently under investigation in phase 2 studies combination treatment may become a viable option (47).…”

Treatment of chronic hepatitis D: New advances, old challenges

“…Thus, an effective anti-HDV therapy would require a marked suppression of HBsAg expression, but current therapies for HBV do not achieve this. Lamivudine, a nucleoside analog that potently inhibits HBV replication, has no efficacy on HDV viremia or liver disease activity in patients with chronic hepatitis D. 7,8 Likewise, other antiviral agents such as suramin, acyclovir, ribavirin, and famcyclovir, as well as immunomodulating agents such as steroids, thymosin, levamisole, and thymic humoral factor-gamma 2 have proved ineffective against HDV. 9 Clevudine, another nucleoside analog that potently suppresses HBV replication, 10 was recently shown to suppress HDV replication in the woodchuck model.…”