Treatment of hepatitis D

Abstract

Delta virus related chronic hepatitis is difficult to treat. The response to alpha-interferon (IFN), which still represents the only therapy for chronic hepatitis D, varies widely and occurs at different times from the beginning of treatment. The rate of response is proportional to the dose of IFN, with 9 million units (MU) three times a week being more effective than 3 MU thrice weekly. Sustained responses are unusual and are accompanied by the clearance of serum hepatitis B virus surface antigen (HBsAg), seroconversion to anti-HBs and improvement of liver histology. Although disease of a short-standing may respond better to therapy, clear predictors of response are still unidentified. Besides IFN, other therapeutic approaches such as immunosuppressive drugs, acyclovir, ribavirin and thymosin, have been unhelpful. Available evidence does not support the use of deoxynucleotide analogues. Famciclovir has no effect on disease activity and hepatitis D virus (HDV)-RNA levels. Twelve- or 24-month lamivudine treatment does not significantly affect biochemical, virological or histological parameters. Pegylated-IFN could represent a reasonable therapeutic option in the long-term treatment required for chronic hepatitis D. Antisense oligonucleotides and prenylation inhibitors hold promise as therapeutic agents of the future. Liver transplantation provides a valid option for end-stage HDV liver disease; the risk of re-infection is lower for HDV than for HBV under long-term administration of hyperimmune serum against HBsAg. Molecularly tailored drugs capable of interfering with crucial viral replicative processes of HDV appear to be the best prospect in the treatment of hepatitis D.

Delta Hepatitis

“…Clinical manifestations of HBV and HDV coinfection could range from mild to severe fulminant hepatitis. If fulminant hepatitis occurs during the acute hepatitis D, liver transplantation is the only treatment option [3,5,6,63]. At present, interferon is the only option for the treatment of chronic hepatitis D. Since most patients have advanced disease and cirrhosis, the response rate to interferon (IFN) therapy is not high (less than 10% with 1-year IFN therapy [63][64][65]).…”

“…If fulminant hepatitis occurs during the acute hepatitis D, liver transplantation is the only treatment option [3,5,6,63]. At present, interferon is the only option for the treatment of chronic hepatitis D. Since most patients have advanced disease and cirrhosis, the response rate to interferon (IFN) therapy is not high (less than 10% with 1-year IFN therapy [63][64][65]). Therapeutic efficacy increases when higher dose of interferon alpha is administered for prolonged periods (12-24 months) [63][64][65][66].…”

“…Some of the most relevant trials about the therapy of chronic HDV infection are summarized in Table I. Liver transplantation is the best treatment option for end-stage liver disease in HDV infection as in other causes of chronic liver diseases [3,63]. Post-transplant course of chronic HDV infection is good, the risk of re-infection is significantly lower for HDV than for HBV and/or HCV.…”

“…At present, interferon is the only option for the treatment of chronic hepatitis D. Since most patients have advanced disease and cirrhosis, the response rate to interferon (IFN) therapy is not high (less than 10% with 1-year IFN therapy [63][64][65]). Therapeutic efficacy increases when higher dose of interferon alpha is administered for prolonged periods (12-24 months) [63][64][65][66]. As described in an interesting case report a 12-year high-dose IFN treatment resulted in the complete resolution of HDV infection with remission of liver fibrosis and disappearance of HBV and HDV from serum [67].…”

Treatment of chronic hepatitis D: New advances, old challenges

“…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. 11 Such suppression correlated with decreased levels of woodchuck hepatitis virus surface antigen, consistent with the hypothesis that targeting surface antigen may be an important antiviral strategy against HDV.…”