Lamivudine for chronic delta hepatitis

Abstract

Chronic delta hepatitis is a severe form of chronic liver disease caused by hepatitis delta virus (HDV) infection superimposed on chronic hepatitis B or the hepatitis B surface antigen (HBsAg) carrier state. Therapy of delta hepatitis is currently unsatisfactory. We have evaluated lamivudine (3-thiacytidine), an oral nucleoside analogue with marked effects against hepatitis B, as therapy in 5 patients with chronic hepatitis D. Five men, ages 38 to 65 years, were treated. All had HBsAg, antibody to HDV, and HDV RNA in serum, as well as persistent elevations in alanine aminotransferase (ALT) levels and liver histology showing severe chronic hepatitis with fibrosis or cirrhosis. Lamivudine was given in a dose of 100 mg orally daily for 12 months. Patients were monitored carefully and tested for HBsAg, HBV-DNA and HDV-RNA levels serially during the year of treatment and for 6 months thereafter. Liver biopsies were performed before therapy and repeated after 1 year. Serum levels of HBV DNA fell rapidly in all 5 patients, becoming undetectable even by polymerase chain reaction (PCR) in 4. However, all 5 patients remained HBsAg-and HDV-RNA-positive, and serum ALT levels and liver histology did not improve. All patients tolerated therapy well. When lamivudine was stopped, HBV-DNA levels returned to pretreatment values without a change in disease activity. Lamivudine is a potent inhibitor of HBV-DNA replication, but does not improve disease activity or lower HDV-RNA levels in patients with chronic delta hepatitis. (HEPATOLOGY 1999;30:546-549.)The hepatitis delta virus (HDV) is a small defective RNA virus that replicates only in the presence of hepatitis B surface antigen (HBsAg). 1,2 Chronic HDV infection often results in severe liver disease that progresses to cirrhosis in as many as 70% of patients. 3 All patients with delta hepatitis have HBsAg in serum, but most lack markers of active hepatitis B virus (HBV) replication such as hepatitis B e antigen (HBeAg) and HBV DNA. Diagnosis is suggested by the finding of anti-HDV in an HBsAg-positive patient and is confirmed by the finding of HDV RNA in serum or HDV antigen in liver. 4 Therapy of chronic delta hepatitis is problematic. Pilot studies suggested that interferon alfa was effective in reducing serum aminotransferase elevations and improving hepatic histology. 5,6 Subsequent randomized, controlled trials showed that interferon was effective in only a proportion of patients and had to be administered in high doses for prolonged periods. [7][8][9][10][11][12] Relapses were common after therapy unless HBsAg was cleared, which occurred uncommonly. 13 Interferon alfa therapy is also expensive, difficult to administer, and often poorly tolerated. Thus, current options for therapy of chronic delta hepatitis are limited.Other antiviral agents have been used in chronic delta hepatitis, but results have been limited. Both ribavirin and levamisole appear ineffective. 14,15 Recently, lamivudine (3-thiacytidine), an oral nucleoside analogue, has been shown to have inhibitory effe...

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

“…Direct anti-HBV agent, such as lamivudine, has been evaluated by Lau et al [49]. It efficiently reduces HBV viremia but not HBsAg levels and has no effect on hepatitis delta, even when associated to IFN [50].…”

Hepatite D

“…Mais recentemente, estudos com a lamivudina em pacientes com hepatite crônica D 25 , na dose de 100mg/dia, por via oral e por um período de 12 meses, revelaram que o medicamento é bem tolerado, com negativação do HBV-DNA em 80% dos casos. Contudo, todos os pacientes tratados permaneceram positivos para o HBsAg e HDV-RNA ao final do tratamento, sempre com ALT alterada e sem remissão do quadro histológico.…”

“…Contudo, todos os pacientes tratados permaneceram positivos para o HBsAg e HDV-RNA ao final do tratamento, sempre com ALT alterada e sem remissão do quadro histológico. Relatam ainda os autores que, após a suspensão da terapêutica, o HBV-DNA voltou a ser detectado no soro 25 . Concluem os autores que a lamivudina revelouse um potente inibidor da replicação do VHB mas mostrou-se incapaz de inibir a replicação do VHD 25 .…”

“…Relatam ainda os autores que, após a suspensão da terapêutica, o HBV-DNA voltou a ser detectado no soro 25 . Concluem os autores que a lamivudina revelouse um potente inibidor da replicação do VHB mas mostrou-se incapaz de inibir a replicação do VHD 25 . A associação da lamivudina e altas doses de Inteferon por um período de 16 semanas também não melhorou a resposta terapêutica.…”

Chronic Hepatitis B with Flare Due to Co-infection of Hepatitis Delta Virus during Lamivudine Therapy

“…However, most patients with chronic HDV infection have antibody to HBe (anti-HBe) and low levels of HBVDNAreplication (8). Liver injury due to HDVmay even occur in CHBpatients undergoing lamivudine therapy; it has reportedly been shownthat lamivudine has no direct effect on HDVreplication (9). In the present case, HBVDNAimmediately decreased to below detectable levels in response to lamivudine therapy, but serum alanine aminotransferase (ALT)rose to above the pretreatment level.…”