Patterns of hepatitis delta virus reinfection and disease in liver transplantation

Ottobrelli, A.; Marzano, Alfredo; Smedile, Antonina; Recchia, S.; Salizzoni, Mauro; Cornù, C.; Lamy, M; Otte, Jean Bernard; Hemptinne, Bernard de; Geubel, André; Grendele, M.; Colledan, M.; Galmarini, D.; Marinucci, G.; Giacomo, C. Di; Agnes, Salvatore; Bonino, Ferruccio; Rizzetto, Mario

doi:10.1016/0016-5085(91)90404-9

Cited by 149 publications

(91 citation statements)

References 12 publications

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“…Replication of HDV independent of hepatitis B has been shown to occur in vitro in cell culture as well as in vivo in patients after liver transplantation. 27 However, without HBV, delta replicates at low levels only, virions are not exported, and infection does not result in widespread infection or cell damage. These findings indicate that it is not HBV replication so much as production of HBsAg that is important in the disease expression and transmission of delta hepatitis.…”

Section: Discussionmentioning

confidence: 99%

“…Patient 3 was referred for liver transplantation, whereupon the decision was made to maintain him on lamivudine (Epivir: 150 mg/d) in preparation for transplantation as prophylaxis against recurrence of hepatitis B. 27 Subsequently, this patient had further deterioration of hepatic synthetic function despite improved ALT level (Fig. 1B), and developed ascites and variceal hemorrhage.…”

Section: Biochemical Virological and Histological Changes Duringmentioning

confidence: 99%

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Lamivudine for chronic delta hepatitis

et al. 1999

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Biochemical Virological and Histological Changes Duringmentioning

confidence: 99%

Lamivudine for chronic delta hepatitis

et al. 1999

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“…8 This infection pattern was described in 30% to 60% of transplantation patients who experienced either acute hepatitis type D or intermittent HDV viremia without hepatitis during the follow-up period. 9,10 The peculiar features of the apparently isolated HDV infection were: 1) the detection of HDAg but not HBV antigens in the liver shortly after transplantation, and before either HDV or HBV was detectable in the serum by standard blotting methods; and 2) the detection of HDV in the serum without evidence of HBV DNA or HBsAg by standard blotting and enzyme immunoassay methods. These features differed from the serological patterns observed in either coinfection or superinfection, in which markers of HBV infection are detected or are in place before those of HDV infection.…”

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confidence: 99%

Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope

et al. 1998

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Hepatitis delta virus (HDV) is a naturally occurring subviral satellite of hepatitis B virus (HBV). 1 The HDV virion is composed of HDV RNA, hepatitis delta antigen (HDAg), and hepatitis B surface antigen (HBsAg), provided as the HBV helper function. Although HDV is able to replicate its RNA within cells in the absence of HBV, 2 HBsAg is required for packaging and release of HDV virions, 3,4 as well as for infectivity. 5 As a result, HDV infects individuals only in association with HBV. Thus, the two commonly described modes of HDV infection are acute coinfection with both viruses and superinfection of HBV carriers with HDV. Acute HBV/HDV coinfection usually resolves, but is more often associated with fulminant hepatitis than is acute HBV infection alone. HDV superinfection of HBV carriers leads to chronic type D hepatitis, which advances to cirrhosis and liver failure more rapidly than viral hepatitis caused by HBV alone. 1 Consequently, although HDV infection affects only a fraction of HBV cases, the resulting acute or chronic liver failure is a relatively more common indication for liver transplantation in Europe as well as North America. 6,7 Curiously, liver transplantation has a better prognosis in patients with terminal cirrhosis caused by HDV than in those with cirrhosis caused by HBV alone. Thus, even though the graft is often reinfected in both cases, HBV/HDV reinfection results in hepatitis and liver disease in only 50% of cases, whereas reinfection with HBV alone is associated with hepatitis in virtually 100% of patients.The patterns of HDV reinfection observed in transplanted livers initially suggested a third mode of HDV infection, which has been referred to as an autonomous, or ''isolated,'' HDV infection. 8 This infection pattern was described in 30% to 60% of transplantation patients who experienced either acute hepatitis type D or intermittent HDV viremia without hepatitis during the follow-up period. 9,10 The peculiar features of the apparently isolated HDV infection were: 1) the detection of HDAg but not HBV antigens in the liver shortly after transplantation, and before either HDV or HBV was detectable in the serum by standard blotting methods; and 2) the detection of HDV in the serum without evidence of HBV DNA or HBsAg by standard blotting and enzyme immunoassay methods. These features differed from the serological patterns observed in either coinfection or superinfection, in

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“…[1][2][3][4][5][6][7] Patients with hepatitis B undergoing OLT without effective prophylactic regimens have a high risk for recurrent infection and hepatitis. Although graft reinfection is almost universal in patients with detectable hepatitis B e antigen (HBeAg) or HBV DNA in serum at the time of OLT, its incidence also is high (50% to 75%) among patients without these markers of viral replication.…”

Section: Natural Historymentioning

confidence: 99%

“…Although graft reinfection is almost universal in patients with detectable hepatitis B e antigen (HBeAg) or HBV DNA in serum at the time of OLT, its incidence also is high (50% to 75%) among patients without these markers of viral replication. [4][5][6] The majority of immunosuppressed liver transplant recipients with recurrent HBV infection develop an aggressive form of chronic hepatitis evolving to cirrhosis or graft failure within 1 or 2 years. 2,4,7 In 1991, Davies et al 4 introduced the term fibrosing cholestatic hepatitis to describe a unique and uniformly fatal form of HBV recurrence.…”

Section: Natural Historymentioning

confidence: 99%

Hepatitis B: Progress in the last 15 years

Villamil

2002

Liver Transplantation

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Patterns of hepatitis delta virus reinfection and disease in liver transplantation

Cited by 149 publications

References 12 publications

Lamivudine for chronic delta hepatitis

Lamivudine for chronic delta hepatitis

Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope

Hepatitis B: Progress in the last 15 years

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