Current issues and treatment of fulminant hepatic failure including transplantation in Hong Kong and the Far East

In the Far East, fulminant hepatic failure is mainly due to viral hepatitis. In areas where hepatitis B infection is endemic, exacerbation of chronic hepatitis B infection, either spontaneously or on withdrawal of immunosuppressive therapy, is the major cause of fulminant hepatic failure. For hepatitis B surface antigen (HBsAg)-positive patients treated with intense immunosuppressive or cytotoxic therapy, preemptive use of lamivudine has drastically reduced the incidence of hepatitis due to hepatitis B exacerbation. Recently, the application of orthotopic liver transplantation, in particular living donor liver transplantation, has markedly improved the survival of patients with fulminant hepatic failure. In Hong Kong, the phenomenon of adoptive transfer of immunity to hepatitis B virus in liver transplantation has recently been reported. The mechanisms by which transfer of immunity occurs and its potential relationship with grafts from living related donors should be further explored.     

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.     

Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region

Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.     

Lamivudine treatment failure in preventing fatal outcome of de novo severe acute hepatitis B in patients with haematological diseases

BACKGROUND: Patients with malignant haematological diseases administered or no longer receiving immunosuppressive therapy are at high risk of reactivation or de novo hepatitis B infection and fulminant hepatitis. Despite promising results in the treatment of chronic hepatitis and its use in selected patients with acute hepatitis B, there is no consensus on lamivudine treatment in severe acute hepatitis portending a fatal clinical outcome. CASE REPORTS: Of the ten patients with malignant haematological disorders who became infected with the same strain of hepatitis B virus during hospitalisation in a haematology ward, five received lamivudine (and in some cases, ganciclovir and famciclovir). The other patients received only supportive therapy, since deteriorating clinical conditions hampered specific treatment efforts. Eight patients died from acute liver failure and one from a fatal course of the haematological disease; one had a favourable outcome from the therapy. There was no significant difference in terms of survival between the treated and untreated patients. CONCLUSIONS: Although lamivudine has proved promising in the therapy of chronic hepatitis B and of recurrent hepatitis after liver transplantation, its use in de novo severe acute hepatitis should be investigated further, particularly in immunocompromised patients.     

The role of lamivudine and predictors of mortality in severe flare-up of chronic hepatitis B with jaundice

summary . Patients with chronic hepatitis B (CHB) may develop severe disease exacerbations (flare) with jaundice, and some may progress to fulminant hepatic failure. Whether early administration of lamivudine can prevent liver failure and mortality is uncertain. We investigated the role of lamivudine treatment in severe hepatitis B virus (HBV) exacerbations. Consecutive patients presented with severe flare-up of HBV (new onset of jaundice plus alanine aminotransferase greater than five times upper limit of normal) treated with lamivudine and historical controls who did not receive lamivudine were studied. All patients had no hepatic encephalopathy on admission. Univariate analysis and multivariate logistic regression were performed on various clinical and laboratory factors for the prediction of mortality. Twenty-eight patients treated with lamivudine and 18 controls were identified. Overall, nine patients died and two other received liver transplants for fulminant hepatic failure. Six of 28 (21.4%) lamivudine-treated patients vs five of 18 (27.8%) controls died or received a liver transplant ( P =0.62). On multivariate analysis, platelet ≤143 × 10E9/L (odds ratio 22.4, 95% CI 1.8–281.6) and bilirubin > 172 μmol/L (odds ratio 18.4, 95% CI 1.5–228.5) were independent predictors of liver-related mortality. The mortality of patients who had thrombocytopenia and high bilirubin, thrombocytopenia, high bilirubin, and no risk factor were 69.2%, 11.1%, 12.5% and 0% respectively. Hence lamivudine confers no survival benefit to conventional treatment in severe exacerbations of CHB. Patients with thrombocytopenia and high bilirubin should be considered for liver transplantation.     

Serological markers in fulminant hepatitis B.

Serological markers for hepatitis B virus infection have been examined in 34 patients with acute hepatitis B, 17 of whom developed fulminant hepatic failure. Hepatitis B surface antigen concentrations were significantly lower and hepatitis Be antigen was less frequently detectable in patients with fulminant hepatic failure compared with those with acute hepatitis (median 0.64 micrograms, range 16-0 and median 32 micrograms and range 100-4 micrograms respectively, p less than 0.001; HBeAg detected in 12% and 88% respectively, p less than 0.001). The IgM component of hepatitis B core antibody was significantly higher in the patients with fulminant hepatic failure with median values of 500 IU/ml compared with those with uncomplicated hepatitis (median 202 IU/ml, p less than 0.05 Wilcoxon's rank test). Three patients who developed a fulminant course had detectable levels of either anti-HBs or anti-HBe. These results are consistent with enhanced antibody responses to all three hepatitis B virus antigens and more rapid clearance of the latter during fulminant hepatic failure.     

The use of lamivudine for patients with acute hepatitis B (a series of cases)

There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 10(5) to 10(7) copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58-year-old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow-up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.     

Interferon and cyclosporin A in the treatment of fulminant viral hepatitis

The prognosis of fulminant hepatitis due to non-A, non-B virus infection and acute reactivation of hepatitis B virus in HB carriers is generally poor, and the treatment of choice in Western countries is recognized as liver transplantation. In countries such as Japan where liver transplantation is not readily available, however, these intractable types of fulminant hepatitis have to be treated medically. Based on the assumption that persistent replication of causal viruses and enhanced host immune responses, especially cellular immunity, to eradicate the viruses are the key mechanism in progressive liver cell destruction and the poor prognosis, we attempted a combination treatment with interferon and cyclosporin A for these types of fulminant viral hepatitis. Subjects in the present study consisted of 1 patient with acute severe hepatitis without coma and 13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B virus and acute reactivation of hepatitis B virus. The patients were given interferon-beta, 300 × 10⁴U daily, and cyclosporin A, at an initial dose of 3 mg/kg, with tapering. Fourteen patients with coma received artificial liver support that we devised. The patient with acute severe hepatitis survived, showing histologically remarkable liver regeneration. Eight of the 14 patients with hepatic coma, all of whom were indications for liver transplantation according to the criteria of the King's College group, survived. Decreased transaminase level, increased liver volume, and histological liver regeneration were observed in all the survivors. The combination of interferon and cyclosporin A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and acute reactivation of hepatitis B virus in HB carriers.     

Severe acute exacerbation of chronic hepatitis B: A unique presentation of a common disease

Severe acute exacerbation is a unique presentation of chronic hepatitis B characterized by very high alanine aminotransferase level accompanied by jaundice and hepatic decompensation. The underlying pathogenesis is likely related to excessive immune clearance, which may be related to the genotype of hepatitis B virus. The mortality is very high once hepatic encephalopathy develops, but some patients can recover to almost normal liver function in contrast to patients with end-stage liver cirrhosis. This condition should be differentiated from acute hepatitis B and other causes of acute hepatitis must be excluded. Conventional prognostic systems may not be applicable to severe acute exacerbation of chronic hepatitis B. In general, patients who have thrombocytopenia, hyperbilirubinemia and coagulopathy have a higher risk of mortality regardless of the serum alanine aminotransferase levels. There is no evidence that lamivudine treatment can reduce the short-term mortality of severe acute exacerbation. However, patients with severe acute exacerbation tend to have a higher rate of maintained virological response, higher rate of hepatitis B e antigen seroconversion and low rate of drug resistance on extended lamivudine treatment as compared to other chronic hepatitis B patients. Virological relapse and severe hepatitis reactivation is common after treatment cessation and therefore long-term antiviral treatment is recommended. Liver transplantation, particularly living donor liver transplantation, should be considered for patients who develop hepatic failure secondary to severe acute exacerbation.     

Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection

BACKGROUND/AIMS: Lamivudine is highly effective in suppressing hepatitis B viral replication and hepatic necroinflammatory activity. The potential for recovery of hepatic decompensation in patients with chronic hepatitis B infection treated with lamivudine has not been established. The aim of this study was to evaluate the effectiveness of lamivudine treatment in severely decompensated cirrhosis due to chronic hepatitis B. METHODS: Thirteen consecutive patients with chronic hepatitis B infection, Child's-Pugh-Turcotte (CPT) score of > or =10 (median score=11) and detectable circulating hepatitis B DNA (range 15 to 9634 pg/ml) were included and treated with lamivudine 150 mg once daily. Hepatitis B envelope antigen (HBeAg) was positive in 9 of 13 patients pre-treatment. RESULTS: Two patients underwent liver transplantation at 4 and 6 weeks after starting lamivudine treatment. The remaining 11 patients were followed for a mean of 17.5 months without liver transplantation (range 3 to 39 months). Significant improvement of liver function, defined as a decrease in CPT score of > or =3, was observed in 9 of 13 patients (69%). In five patients, CPT score improved to <7 and they were placed on the inactive status (UNOS status 7) for liver transplantation. Hepatitis B DNA remained negative in all except one patient who developed breakthrough viral replication 12 months after starting lamivudine treatment, while maintaining stable liver function. Three of seven HBeAg-positive patients who did not undergo liver transplantation lost HBeAg during follow-up, but none had sustained seroconversion to hepatitis B e antibody. CONCLUSION: Lamivudine appears highly effective in reversing severe hepatic decompensation due to replicating hepatitis B infection.     

Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin's lymphoma

We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkin's lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkin's lymphoma.     

Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.     

Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Lamivudine Transplant Group

Hepatitis B after liver transplantation is often fatal, and no proven medical therapy exists for this condition. We chose to study the potential efficacy of lamivudine therapy for patients with chronic hepatitis B after liver transplantation. Fifty-two patients with chronic hepatitis B after liver transplantation were treated in an open label, multicenter study. Each had detectable hepatitis B virus (HBV) DNA in serum and 45 (87%) had detectable serum hepatitis B e antigen before treatment. Patients were treated for 52 weeks with lamivudine (100 mg daily). The primary endpoint was undetectability of HBV DNA; secondary endpoints included normalization of serum alanine transaminase (ALT) levels, disappearance of hepatitis B e antigen, and improvement in liver histology. After treatment, 60% of patients had undetectable HBV DNA by solution hybridization assay, 14 (31%) of the initially positive patients lost hepatitis B e antigen; hepatitis B surface antigen was undetectable in 3 (6%); and serum ALT levels normalized in 71%. Blinded histological assessments showed improvement in the histological activity index (P =.007 for periportal necrosis,.001 for lobular necrosis, and.013 for portal inflammation). YMDD variants of HBV, potentially associated with drug resistance, were detected in 14 (27%) of the patients. Repeat liver biopsies in 7 patients with the mutated virus were unchanged in 2, improved in 2, and worse in 3. We conclude that lamivudine is a potentially effective therapy for hepatitis B after liver transplantation.     

Fatal Fulminant Hepatitis B after Withdrawal of Prophylactic Lamivudine in Hematopoietic Stem Cell Transplantation Patients

Hepatitis B virus (HBV) reactivation can give rise to acute hepatitis and even fatal fulminant hepatitis in patients receiving immunosuppressive or cytostatic treatment. Recently, the prophylactic use of lamivudine for HBV reactivation in HBV surface antigen-positive chronic-disease patients undergoing hematopoietic stem cell transplantation (HSCT) has been reported. However, the appropriate duration for this prophylactic therapy is unclear. Here, we report 2 cases of fatal fulminant hepatitis B reactivation in HSCT patients after lamivudine withdrawal. One patient with non-Hodgkin's lymphoma completed 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and autologous peripheral blood SCT (PBSCT). Lamivudine was discontinued 3 months after transplantation. The second patient had acute myeloid leukemia. He received induction chemotherapy and postremission allogeneic PBSCT as late intensified consolidation therapy. Lamivudine treatment was discontinued 10 months after transplantation. In both patients, HBV reactivation 2 to 3 months following lamivudine cessation led to fatal fulminant hepatitis. We suggest that the duration of prophylactic use of lamivudine in chronic HBV carriers receiving HSCT be prolonged until the patient's immune system has been reconstituted.     

Acute liver failure and the Molecular Adsorbents Recirculating System: early experience in a tertiary care hospital in Mexico City

Acute liver failure is a clinical condition associated with high mortality despite recent technological advances. Supportive devices such as the Molecular Adsorbents Recirculating System (MARS) provide therapeutic strategies to add time to find an organ for orthotopic liver transplantation or to allow the native liver to recover sufficiently to make transplantation unnecessary. In this series of cases, we discuss our initial experiences with three patients with acute liver failure. One patient had high bilirubin levels caused by Epstein-Barr virus infection and responded well after three MARS sessions. In a second patient, MARS therapy was used to treat acute-on-chronic liver failure caused by chronic hepatitis B virus infection that had not been treated previously; because of severe hemodynamic compromise, only one MARS session was performed. The third patient had an initial diagnosis of acute liver failure and cryptogenic hepatitis, and was treated with five MARS sessions as a supportive measure until the definitive diagnosis (metastatic disease) was performed. In all patients, MARS therapy was well tolerated and induced only mild hypokalemia. In conclusion, although MARS therapy was an effective strategy for these cases of liver failure and greatly improved the biochemical variables, its impact on the mortality rate has not yet been determined.     

Fatal reactivation of hepatitis B virus following cytotoxic chemotherapy for acute myelogenous leukemia: fibrosing cholestatic hepatitis

Hepatitis B virus (HBV) is a well known pathogen that sometimes causes fulminant hepatitis in patients undergoing cytotoxic chemotherapy. Fibrosing cholestatic hepatitis (FCH) is a recently recognized unique variant of viral hepatitis, which has been occasionally reported in HBV-infected recipients of liver, renal, or bone marrow transplantation. We present here a 48-yr-old male in whom HBV was reactivated during post-remission chemotherapy for acute myelogenous leukemia, which resulted in rapidly fatal outcome. He manifested with deterioration of liver function in association with enormous replication of HBV. Liver biopsy showed marked ballooning of hepatocytes, cholestasis, and periportal fibrosis with minimum infiltrates. Immunostaining revealed that hepatocytes were strongly positive for hepatitis B surface antigen. Under the diagnosis of FCH, he was treated with lamivudine and interferon beta, which was not effective. Autopsy showed severe atrophy of the liver and marked degeneration of hepatocytes. Hematologists should be aware that FCH is a fatal complication that can develop under post-chemotherapy immunosuppressed conditions. Although there is no convincing evidence, prophylactic administration of lamivudine seems to be a reasonable strategy.     

Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated with lamivudine

Fibrosing cholestatic hepatitis (FCH) is a rare and extremely severe form of hepatitis B virus (HBV) infection. This condition was originally described in HBV-infected recipients after a liver transplantation. Recently, FCH has been reported not only in liver transplant recipients, but also in other immunosuppressed patients. It is characterized clinically by cholestatic hepatic dysfunction, and pathologically by severe periportal fibrosis, cholestasis, widespread balloon degeneration of hepatocytes, and only a mild infiltration of inflammatory cells. Without treatment, FCH is universally fatal within a few months of diagnosis. There have been only two isolated case reports of FCH with long-term patient survival, and one case report with treatment failure after lamivudine therapy. Because of the rarity of this clinical entity, the therapeutic efficacy of lamivudine in patients with FCH cannot be evaluated systematically. Here, we present four patients with HBV-related FCH treated with lamivudine. One received antineoplastic therapy for acute lymphoblastic leukemia, and the other three were renal graft recipients. Two patients who developed FCH after a renal transplantation survived with an improvement in liver function and were followed up for 20 and 30 months, respectively, and were found to be in good health. However, the other two patients died of sepsis, possibly as a consequence of the immunosuppression with hepatic failure despite lamivudine treatment. Our experience suggests that lamivudine can alter the grave natural history of FCH.     

Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients

Hepatitis B virus (HBV) reactivation is a well-known complication of lymphoma treatment in the pre-rituximab era. This complication has not been as well studied, however, since monoclonal anti-CD20 antibody became the standard regimen for B cell lymphoma. In this retrospective study, 115 B cell lymphoma patients who received rituximab-containing therapy were analyzed. Of 15 hepatitis B surface antigen (HBsAg)-positive patients, five received lamivudine prophylaxis and did not develop HBV-related hepatitis during lymphoma treatment. Eight of ten HBV carriers without lamivudine prophylaxis experienced HBV-related hepatitis, including one fatal hepatic failure. Four (4.2%) of 95 HBsAg-negative patients developed de novo HBV-related hepatitis and two died of fulminant hepatitis. In conclusion, rituximab-based therapy may cause serious HBV-related complications and even death in both HBsAg-positive and HBsAg-negative patients.     

Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation,and review of the literature

OBJECTIVES: To analyse the results of lamivudine therapy on suppression of hepatitis B virus (HBV) replication before transplantation and on preventing graft reinfection postoperatively. DESIGN: Long-term clinical study. SETTING: Liver Institute and Department of Transplantation of a tertiary-care university-affiliated centre. SUBJECTS: (1) 14 candidates for liver transplantation with decompensated liver disease caused by active replication of HBV; (2) six patients with recurrent HBV infection after transplantation. INTERVENTION: Lamivudine 100 mg daily; administered in group 1 before surgery and continued after in nine patients who underwent transplantation; administered in group two postoperatively only. anti-hepatitis B surface antigen immunoglobulin (HBIg) was administered postoperatively in both groups. MAIN OUTCOME MEASURES: Immunoassay evaluation of serum hepatitis B surface antigen, serum hepatitis Be antigen and serum HBV DNA (hybridization and PCR); sequencing through the tyrosine-methionine-aspartate-aspartate locus of the HBV polymerase gene in patients with lamivudine breakthrough; inflammation and fibrosis scoring on liver biopsy before and at least 2 years after lamivudine therapy in group 2. RESULTS: Pretransplantation therapy (group 1) significantly suppressed HBV replication and enabled nine patients (64.2%) to undergo transplantation. Only one patient (7.1%) had lamivudine breakthrough, and one (7.1%) had recurrent HBV. Lamivudine administration begun after transplantation (mean 48.0 months, range 30-60 months) because of graft reinfection (group 2) was associated, over the long-term, with the emergence of high mutation rates (83.3%), histological disease progression (66.6%), and hepatic failure (33.3%). CONCLUSIONS: In patients with chronic HBV infection and active viral replication, lamivudine therapy is effective when started before transplantation. However, its long-term administration after transplantation for recurrent HBV leads to high resistance rates. Combination therapy with lamivudine and HBIg immunoglobulin can substantially reduce the recurrence rate. Further studies on combination antiviral therapy are needed in this patient population.     

Lamivudine treatment for acute severe hepatitis B: report of a case and review of the literature

The oral nucleoside analogue lamivudine has been effectively used in the treatment of chronic hepatitis B. However, there is limited data concerning the efficacy and safety of lamivudine in patients with severe acute or fulminant hepatitis B. We report the use of lamivudine in a young woman with acute HBV infection and fulminant hepatic failure. Following lamivudine treatment, we noticed a prompt clinical, biochemical, serological and virological response as it was seen in the vast majority of, previously reported, cases. Lamivudine treatment was continued until HBsAg was cleared. Our case, as well as previously reported ones, suggests that lamivudine may have a beneficial effect in selected patients with acute severe or fulminant HBV infection.