Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log 10 reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV. (HEPATOLOGY 2000;32:129-134.)recently has been licensed in the United States, Canada, Europe, and Asia for the treatment of chronic hepatitis B. This drug has been shown to be highly effective in inhibiting hepatitis B virus (HBV) replication. [1][2][3][4] Clinical trials have provided evidence for histologic improvement as well as rates of hepatitis B e antigen (HBeAg) disappearance and seroconversion to anti-HBe that are similar to those observed with interferon alfa therapy. [1][2][3][4] One of the observations common to all of these studies, however, is the emergence of lamivudineresistant HBV mutants that undergo mutation in the HBV DNA polymerase gene. Two types of mutation have been identified to account for lamivudine resistance. 5 Mutation at codon M552 of the YMDD motif results in substitution of isoleucine for methionine (M552I). An alternate mutation at this site results in substitution of methionine by valine (M552V). The M552V mutation is accompanied by a second mutation at codon 528 that results in the substitution of leucine by methionine (L528M). In a recent analysis of data from the phase III trials of lamivudine, Atkins et al. 6 reported that resistance to lamivudine developed in 16% to 32% of patients after 1 year of treatment. 6 More recently, resistance has been shown to occur in 38% and 49% of patients after 2 and 3 years of treatment, respectively. 7,8 The natural history of hepatitis B in this situation is not yet well defined, but there have been well documented cases in which clinical and histologic progression has occurred after liver transplantation, including rapid progression to cir...

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These data suggest that de novo sirolimus-based immunosuppression is associated with satisfactory outcomes after transplantation, even in selected patients beyond Milan criteria. The protocol has proven safe, with an acceptable side-effect profile. This study supports the conduct of larger randomized trials investigating sirolimus after transplantation for HCC.

Liver transplantation for endstage hepatitis B virus (HBV) infection has been associated with survival inferior to that of liver transplantation in other chronic liver diseases due to HBV reinfection of the graft. Lamivudine is a new nucleoside analog with potent antiviral effects against hepatitis B. Our aim was to test its efficacy when used pre- and posttransplantation in HBV-DNA positive patients with endstage liver disease. Patients received oral lamivudine 100 mg daily both pretransplant and posttransplant. Viral serology, serum and tissue HBV-DNA and liver histology were assessed sequentially. Five consecutive patients with endstage hepatitis B were entered into the trial. Serum HBV-DNA was cleared pretransplant in all patients. Three of four transplanted patients cleared HBeAg and HBsAg postoperatively, whereas all four became negative for serum HBV-DNA (dot-blot and PCR). Liver biopsies were negative for HBV-DNA by PCR in 3 of 4 cases. Lymphocytes were negative for HBV-DNA by PCR in all cases. With follow-up of 3, 14, 16, and 26 months, two patients have normal liver enzymes and normal liver histology and two have developed recurrent hepatitis B. No significant side effects were seen. This pilot study shows that lamivudine can effectively inhibit hepatitis B virus in cirrhotic patients pretransplant and posttransplant. A lamivudine resistant mutant developed in two patients. Transplant recipients with actively replicating HBV related cirrhosis may achieve a good outcome after liver transplantation using lamivudine, but viral resistance is likely to be a significant problem.

To our knowledge, this is the first study of prolonged midodrine, octreotide and albumin therapy in RA. We observed a significant reduction in the plasma renin and aldosterone concentrations and a trend towards a reduction in the volume of ascites removed by paracentesis without an effect on renal function. The beneficial effects are at the expense of a reversible deterioration in the MELD score. Large controlled trials are needed before this therapy can be routinely recommended.