Complete Virological Response Research Articles

Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation

AbstractHepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B-cell lymphoproliferative disorders (LPDs). The t(14;18) translocation may play a pathogenetic role. Limited data are available regarding the effects of antiviral therapy on rearranged B-cell clones. We evaluated the effects of interferon and ribavirin on serum, B-lymphocyte HCV RNA, and t(14; 18) in 30 HCV+, t(14;18)+patients without either mixed cryoglobulinemia syndrome or other LPDs. The t(14;18) translocation was analyzed by bothbcl-2/JHpolymerase chain reaction andbcl-2/JHjunction sequencing in peripheral blood mononuclear cells in all patients. Fifteen untreated patients with comparable characteristics served as controls. Throughout the study, the presence or absence of both t(14;18) and HCV RNA sequences were, in most cases, associated in the same cell samples. At the end of treatment, t(14;18) was no longer detected in 15 patients (50%) with complete or partial virologic response, whereas it was persistently detected in nonresponders (P< .05), as well as in 14 of 15 control patients. In 4 responder patients, t(14;18) and HCV RNA sequences were no longer detected in blood cells after treatment, but were again detected after viral relapse; the same B-cell clones were involved in the pretreatment and posttreatment periods. In conclusion, this study suggests that antiviral therapy may induce regression of t(14;18)–bearing B-cell clones in HCV+patients and that this phenomenon may be related, at least in part, to the antiviral effect of therapy. This in turn suggests that antiviral treatment may help prevent or treat HCV-related LPDs.

Excellent outcome of Lamivudine treatment in patients with chronic renal failure and hepatitis B virus infection.

Chronic hepatitis B virus (HBV) is associated with increased morbidity and mortality in patients with chronic renal failure (CRF) and renal transplant recipients. Lamivudine (3TC) has been shown to be a potent inhibitor of HBV replication. It appears to be safe and effective in patients with CRF, though experience is still limited. We describe 4 patients with CRF on hemodialysis who showed a rapid and full response to 3TC, administered for a median of 10 months. All patients had serum alanine transferase (ALT) levels 3 to 6 times the upper limit of normal prior to treatment, and different degrees of histologic inflammatory activity (Knodell score 4 to 8, median 6). All were serum HBsAg- and HBeAg-positive, with serum HBV DNA 1-3.9 x 107 copies/mL (median 1 x 107 copies/mL). Within 4 to 8 weeks of initiation of therapy, HBV DNA became undetectable and serum ALT normalized. Serum HBeAg disappeared in all 4 patients, with the emergence of anti-HBeAb in 3 of them. Three patients also lost HBsAg with the evolution of a protective anti-HBsAb titer. One patient has already undergone successful kidney transplantation with no evidence of HBV recurrence (serum HBV DNA negative) 16 months postoperatively. Although our study sample is small, these data suggest that 3TC can induce a complete biochemical, virological and serological response in patients with CRF and HBV infection. Its use may enable safe kidney transplantation in selected patients.

THROMBOCYTOPENIA IN PATIENTS WITH HCV‐POSITIVE CHRONIC HEPATITIS: EFFICACY OF LEUCOCYTE INTERFERON‐α TREATMENT

SUMMARYTreating patients with HCV‐associated thrombocytopenia is a problem, because the pathogenesis of thrombocytopenia is still unclear. We evaluated the clinical and haematological response to leucocyte interferon‐α in 20 naive patients with chronic hepatitis C and thrombocytopenia (platelet count &lt;140 × 109/l for at least six months) without portal hypertension and/or hypersplenism. They were treated with leucocyte interferon‐α (3 MU three times per week) for 12 months and followed up for 12 months. Biochemical (ALT) and virological (HCV‐RNA) responses were determined. Two patients discontinued treatment because of hyperthyroidism. Of the 18 patients who completed treatment, 12 (66%) showed a biochemical response, 10 of whom (55.5%) also showed a virological response. At the end of follow‐up, four patients (22%) showed a complete (biochemical and virological) response. During treatment, platelet counts decreased to less than 10–20% of pretreatment values in most patients. Three of the four patients with a complete response showed a platelet increase during treatment and throughout the follow‐up period. In HCV‐associated thrombocytopenia leucocyte interferon‐α is well tolerated and in cases of sustained virological inhibition is able to ameliorate the disease by increasing the platelet count.

Interferon Therapy for Acute Hepatitis C During Pregnancy

OBJECTIVE:Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome.CASE SUMMARY:A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology.DISCUSSION:The rate of transmission of hepatitis C virus from mother to infant is within the range of 1–5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations.CONCLUSIONS:Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.

Drug Treatment of Pediatric Chronic Hepatitis B

Children with chronic hepatitis B are at risk of developing long-term complications such as cirrhosis and hepatocarcinoma. It is estimated that half to two-thirds of affected children will clear the hepatitis B e antigen (HBeAg) naturally before reaching adulthood. As in adults, treatments in children accelerate the virological response (DNA negativity and HBeAg loss, with anti-HBe seroconversion), which is associated with normalization of transaminase levels. Treatments also favor subsequent loss of hepatitis B surface antigen (HbsAg), the ultimate goal for minimizing long-term consequences. Interferon-α was the first approved treatment for pediatric chronic hepatitis B, and was shown to promote DNA negativity and HBeAg loss in 26% of treated patients (6 MU/m2 body surface area for 6 months) at 1 year and 33% at 18 months (versus 11% in controls). 10% of treated patients also lost HBsAg. Adverse effects mainly included fever, flu-like symptoms and growth impairment during the treatment phase. Nucleotide analogs have now emerged as promising alternatives for the treatment of chronic hepatitis B. Lamivudine dose-ranging studies showed a higher clearance in children, and the optimal dosage was established to be 3 mg/kg once daily in children up to 12 years of age. Efficacy trials showed complete virological response (HBeAg loss and DNA negativity) in 23% of all treated patients after 1 year, and in 34% of patients with initial transaminase levels >2 × the upper limit of normal. Lamivudine resistance due to mutant/variant viruses is observed in 19% of children after 1 year, a figure that may increase by an average of 20% per year. Other nucleotide analogs, such as adefovir, will soon be tested in children, and have shown promising results in adults without so far demonstrating viral resistance. Finally, therapeutic vaccines aiming to induce a cellular immune response towards hepatitis B antigens are being tested in adults, but no clinical benefit has so far been established.

Drug treatment of pediatric chronic hepatitis B.

Children with chronic hepatitis B are at risk of developing long-term complications such as cirrhosis and hepatocarcinoma. It is estimated that half to two-thirds of affected children will clear the hepatitis B e antigen (HBeAg) naturally before reaching adulthood. As in adults, treatments in children accelerate the virological response (DNA negativity and HBeAg loss, with anti-HBe seroconversion), which is associated with normalization of transaminase levels. Treatments also favor subsequent loss of hepatitis B surface antigen (HbsAg), the ultimate goal for minimizing long-term consequences. Interferon-alpha was the first approved treatment for pediatric chronic hepatitis B, and was shown to promote DNA negativity and HBeAg loss in 26% of treated patients (6 MU/m(2) body surface area for 6 months) at 1 year and 33% at 18 months (versus 11% in controls). 10% of treated patients also lost HBsAg. Adverse effects mainly included fever, flu-like symptoms and growth impairment during the treatment phase. Nucleotide analogs have now emerged as promising alternatives for the treatment of chronic hepatitis B. Lamivudine dose-ranging studies showed a higher clearance in children, and the optimal dosage was established to be 3 mg/kg once daily in children up to 12 years of age. Efficacy trials showed complete virological response (HBeAg loss and DNA negativity) in 23% of all treated patients after 1 year, and in 34% of patients with initial transaminase levels >2 x the upper limit of normal. Lamivudine resistance due to mutant/variant viruses is observed in 19% of children after 1 year, a figure that may increase by an average of 20% per year. Other nucleotide analogs, such as adefovir, will soon be tested in children, and have shown promising results in adults without so far demonstrating viral resistance. Finally, therapeutic vaccines aiming to induce a cellular immune response towards hepatitis B antigens are being tested in adults, but no clinical benefit has so far been established.

Decay of HIV type 1 DNA and development of drug-resistant mutants in patients with primary HIV type 1 infection receiving highly active antiretroviral therapy.

The present study was aimed at describing the effect of highly active antiretroviral therapy (HAART) in 10 patients with primary HIV infection (PHI). Clearance rates of HIV RNA and HIV DNA in peripheral blood as well as the preexistence and the emergence of drug-resistant strains of HIV were determined over 52 weeks of treatment. The data indicate that HAART is able to induce a suppression of plasma viral load together with a significant decrease, but not a suppression, of peripheral blood mononuclear cell-associated proviral DNA in PHI subjects. Analysis of drug-resistant strains revealed that three PHI patients, showing a complete virologic response, developed mutations in the pol gene, thus suggesting that a persistent residual virus replication exists despite a sustained suppression of plasma viremia.

Effect of Prior Nucleoside Use on the Two-Year Virological Response to an Initial Protease Inhibitor Regimen in HIV-Infected Patients

Purpose: This retrospective study investigates the effect of prior nucleoside (nucleoside reverse transcriptase inhibitor [NRTI]) experience on 2-year virologic response to an initial protease inhibitor-highly active antiretroviral therapy (PI-HAART) regimen. Method: 152 patients who started a PI (excluding saquinavir hard gel capsule [hgc] as a sole PI) with two NRTIs between January 1996 and May 1998 at two HIV treatment sites were included. Results: 109 patients (71%) were NRTI experienced. 106 patients received two new NRTIs, and 32 received one new NRTI. Overall, 51% of patients had a virologic response (HIV viral load <400 copies/mL); the mean follow-up was 28 months. Virologic response was associated with the use of at least one new NRTI (relative risk [RR] 2.1; p = .031) but not with prior NRTI experience (p = .19). A complete virologic response was most likely to occur when two new NRTIs were used (RR 2.3) rather than one new NRTI (RR 1.8), but this was not significant (p = .12). Conclusion: This study suggests that prior nucleoside experience is not a key predictor of 2-year virologic response in patients who receive at least one new NRTI in an initial PI-HAART regimen.

Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease

The virological and immunological response to an efavirenz-containing rescue regimen was compared with that of a nevirapine-containing one in a prospective, open-label 12-month study performed in patients previously treated with ≥12 months of nucleoside analogue monotherapy, and ≥15 months of indinavir- or ritonavir-containing HAART. Pooled laboratory data were assessed according to change or continuation of nucleoside analogues, at the time of start of salvage treatment. An improvement of markers of HIV disease progression occurred in all 59 evaluable patients (with a higher viral load decrease in the efavirenz over the nevirapine group at the third month), but the virological response was neither complete nor sustained at the end of study, irrespective of efavirenz or nevirapine adjunct, and complete viral suppression was attained in only 16.9% of subjects. A progressively increasing mean CD4+ lymphocyte count characterized the immunological response of all patients. The 35 patients who changed at least one nucleoside analogue when introducing salvage therapy had a better outcome, irrespective of the non-nucleoside reverse transcriptase inhibitor chosen. Rescue strategies are increasingly needed in HIV-infected patients treated for a long time with HAART. The association of nelfinavir, a non-nucleoside reverse transcriptase inhibitor, and dual nucleoside analogues, is popular among patients who fail first-line HAART. When prolonged prior treatment with nucleoside analogue monotherapy and HAART are of concern, and a quite elevated viral load is present, this salvage regimen may not allow a complete and sustained virological response in a 1-year period, while a more favourable immunological recovery can be expected. However, the concurrent change of nucleoside analogues significantly improves treatment outcome.

Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is common, although the majority of cases are mild. A subset of transplant recipients develops progressive allograft injury, including cirrhosis and allograft failure. Minimal data are available on the safety and efficacy of antiviral treatment in this group of patients. The aim of this study is to review our experience in the treatment of moderate to severe HCV recurrence with combination interferon-alpha2b and ribavirin (IFN/RIB). Between October 1993 and October 1999, a total of 197 patients underwent OLT for HCV-related liver failure. This study describes 12 transplant recipients with moderate to severe recurrence treated with IFN/RIB. All patients met at least 1 of the following inclusion criteria: (1) moderate to severe inflammation (grade III to IV) on allograft biopsy, (2) bridging fibrosis on allograft biopsy, or (3) severe cholestasis attributable solely to HCV recurrence. Two patients had undergone re-OLT for allograft cirrhosis secondary to HCV recurrence and now had evidence of progressive HCV in their second allografts. Appropriate dose reductions of both IFN and RIB, as well as initiation of granulocyte colony-stimulating factor (G-CSF), for marked leukopenia were recorded. IFN/RIB therapy was started 60 to 647 days post-OLT, and duration of therapy ranged from 39 to 515 days. Seven patients were administered G-CSF to successfully treat leukopenia. Six of the 12 patients (50%) became HCV RNA negative by polymerase chain reaction. One of these 6 patients (no. 1) was HCV RNA negative at 6 months but chose to discontinue therapy because of intolerable side effects, experienced a relapse, and was HCV RNA positive at 12 months. Two of the remaining 5 patients were HCV RNA negative at 2 and 9 months off therapy. For the entire group, there was a statistically significant decrease in serum biochemical indices assessed at initiation of therapy and 1, 3, and 6 months into therapy. Most patients required dose reductions of both IFN and RIB. Five patients died; 3 patients died of liver-related complications that included severe intrahepatic biliary cholestasis, severe HCV recurrence, and chronic rejection with profound cholestasis. In the subset of HCV-positive liver transplant recipients with moderate to severe recurrence, combination IFN/RIB therapy resulted in complete virological response (serum RNA negative) in 6 of 12 patients ( approximately 50%). However, only 1 of 12 patients (8.3%) had sustained virological clearance after cessation of IFN/RIB therapy. Dose reductions of both IFN and RIB were required in most patients. The use of G-CSF (sometimes preemptively) allowed correction of leukopenia and full-dose antiviral therapy. Multicenter trials using combination therapy to identify factors predictive of response are needed in the subset of patients with progressive allograft injury.

Detection of Residual Hepatitis C Virus RNA by Transcription-Mediated Amplification in Patients With Complete Virologic Response According to Polymerase Chain Reaction–Based Assays

A considerable proportion of patients with chronic hepatitis C who achieve a virologic end-of-treatment response relapse after discontinuation of therapy. It is conceivable that polymerase chain reaction (PCR)-based assays with a lower detection limit of 100 to 1,000 hepatitic C virus (HCV) RNA copies/mL are still too insensitive to detect residual viremia. End-of-treatment serum samples of 47 patients with a virologic relapse according to results of qualitative PCR assays (Amplicor HCV; Roche Molecular Systems, Mannheim, Germany) were tested by transcription-mediated amplification (TMA), an isothermal, autocatalytic target amplification method that has the potential to detect less than 50 HCV RNA copies/mL. Virologic sustained responders (n = 59) and nonresponders (n = 49) served as controls. In end-of-treatment serum samples of virologic sustained responders and nonresponders an almost complete concordance between PCR and TMA results was observed (98%). However, HCV RNA was detectable by TMA in end-of-treatment serum samples from 16 of 25 relapse patients (64%) who were HCV-RNA–negative according to Amplicor HCV version 1.0 (lower detection limit 1,000 copies/mL) and in 8 of 22 patients (36%) who were HCV-RNA–negative according to Amplicor HCV version 2.0 (lower detection limit 100 copies/mL). End-of-treatment alanine transaminase (ALT) levels of sustained virologic responders and TMA-negative relapsers were similar, whereas a trend toward higher ALT values was observed in TMA-positive relapsers compared with sustained virologic responders (P = 0.09). In conclusion, HCV RNA can be detected at the end of treatment by TMA in a considerable proportion of patients who were classified as virologic end-of-treatment responders with a subsequent virologic relapse according to PCR-based methods.(Hepatology 2000;32:818-823.)

The pattern of response to interferon alpha (α-IFN) predicts sustained response to a 6-month α-IFN and ribavirin retreatment for chronic hepatitis C

Background/Aims: In chronic hepatitis C, interferon-alpha (α-IFN) and ribavirin combination therapy improves sustained response compared to α-IFN monotherapy, both in naive patients and in previous α-IFN relapsers, but the efficacy of such therapy remains limited in non-responder cases. The aim of this study was to assess whether the pattern of response to α-IFN alone may predict sustained response to combination therapy during retreatment. Methods: Fifty previous α-IFN relapsers and 50 previous α-IFN non-responders were retreated with a high α-IFN dose (6 MU/thrice weekly for 2 months; induction phase) and then randomised to continue with α-IFN alone (3 MU/thrice weekly) or to receive combination therapy (3 MU/thrice weekly of α-IFN and 1000–1200 mg/daily of ribavirin) for an additional 6 months according to the biochemical response to α-IFN shown after the induction phase. All patients were also evaluated for virological and histological response. Results: Eleven of 25 (44%) relapsers treated with combination therapy and 4/25 (16%) treated with α-IFN alone achieved a sustained response. The corresponding figures among non-responders were 1/25 (4%) and 0/25, respectively. Among 26 patients with a complete ALT and HCV-RNA response after 2 months of α-IFN, sustained response was seen in 11/14 (79%) treated with combination therapy and in 4/12 (33%) treated with α-IFN alone ( p=0.05). On the other hand, of 74 cases still HCV-RNA positive after 2 months of α-IFN alone, biochemical and virological end of therapy response was better with combination therapy (11/36; 30.5%) compared to α-IFN alone (4/38; 10.5%), but only one patient developed a sustained response (1/36; 3%). Conclusions: The retreatment with a 6-month combination therapy was associated with a high rate of sustained response only in patients showing a complete biochemical and virological response to α-IFN alone. Longer retreatment with combination therapy may be needed to achieve a sustained response in patients without a prompt virological response to α-IFN.

Efficacy of thymosin α1 in patients with chronic hepatitis B: A randomized, controlled trial

Thymosin alpha1 (Talpha) is an immune modifier that has been shown in a pilot study to be effective for chronic hepatitis B; this requires confirmation. Ninety-eight patients with clinicopathologically proven chronic hepatitis B were randomly allocated to 3 groups: 1) group A received a 26-week course of Talpha with a 1.6-mg subcutaneous injection two times a week (T6 group); 2) group B received the same regimen as group A, but Talpha therapy extended for 52 weeks (T12 group); and 3) group C served as a control group and was followed up for 18 months without specific treatment (T0 group). The three groups were comparable in clinicohistological features at entry. The complete virological response rate (clearance of serum hepatitis B virus [HBV] DNA and hepatitis B e antigen [HBeAg]) was higher in group A (40.6%) and group B (26.5%) than in group C (9.4%) (group A vs. group C: P=.004; group B vs. group C: P=.068) when assessed 18 months after entry, although complete response rates among these three groups were similar when first assessed at the end of therapy. There was a trend for complete virological response to increase or accumulate gradually after the end of Talpha therapy. None of the responders lost hepatitis B surface antigen. Blinded histological assessment showed a significant improvement in treated patients, particularly in lobular necroinflammation and scores excluding fibrosis. No significant side effects were observed. These results suggest that a 26-week course of Talpha therapy is effective and safe in patients with chronic hepatitis B.

Interferon-??-n1

Interferon-alpha-n1 (lymphoblastoid interferon-alpha) is a nonrecombinant 'natural' interferon derived from lymphoblastoid cells exposed to Sendai virus. In common with endogenous and recombinant interferon-alpha molecules, interferon-alpha-n1 has antiviral, immunomodulatory and antiproliferative properties. Interferon-alpha-n1 shows some efficacy in immunocompetent adults with well-compensated chronic viral hepatitis B. Rates of complete virological response (defined as an absence of detectable hepatitis B virus-DNA in the serum) ranged from 5 to 79% of adults who received various dosage regimens of interferon-alpha-n1 in monotherapy trials. Clearance of hepatitis B 'e' antigen was reported in 5 to 70% of patients treated with the drug. Spontaneous virological responses occurred in 0 to 48% of untreated patients. The clinical efficacy of interferon-alpha-n1 in patients with chronic hepatitis B is not improved by concomitantly administered deflazacort, zidovudine or levamisole, but may be increased by a course of corticosteroid pretreatment in some patients. Interferon-alpha-n1 also shows therapeutic benefit in adults with chronic hepatitis C. Complete biochemical responses (defined as normalisation of serum ALT levels) were achieved in 27 to 60% of adult patients treated with the drug, whereas spontaneous normalisation of serum ALT levels occurred in up to 11% of untreated patients. Responses to interferon-alpha-n1 were temporary in 27 to 78% of treatment responders but were sustained in 6 to 40% of patients. Emerging data delineating baseline factors predictive of a positive response to interferon-alpha-n1 treatment may aid in the selection of patients with hepatitis B or C most likely to benefit from treatment with this drug. Most patients receiving interferon-alpha-n1 experience a transient 'influenza-like' syndrome during the first week of treatment. The syndrome, which is dose related and alleviated by paracetamol (acetaminophen), is characterised by fever, chills, and arthralgia. Dose-limiting adverse effects occurring during longer term interferon-alpha-n1 therapy include fatigue, myalgia, headache, depression, pruritus and seizures. Neutropenia and thrombocytopenia may also occur during interferon-alpha-n1 treatment. Autoimmune thyroid disease may develop in up to 9% of patients treated with interferon-alpha-n1 for >or=6 months. At present, interferon-alpha-n1 and the recombinant forms of interferon-alpha are the only drugs available for the treatment of adults with well-compensated hepatitis B or C. Interferon-alpha-n1 produces moderate response rates in adults with well-compensated chronic hepatitis B or C. Thus, it is positioned alongside recombinant interferon-alpha products as a useful first-line treatment option for patients with chronic hepatitis B or C.

Interferon alfa for recurrent hepatitis B infection after liver transplantation.

Reinfection with hepatitis B virus (HBV) after liver transplantation is nearly universal in patients not receiving immunoprophylaxis. Because reinfection reduces graft and patient survival, treatment of recurrent infection is important. Interferon alfa (IFN-alpha) is an effective therapy for chronic hepatitis B infection in immunocompetent patients, but its efficacy in transplant recipients has not been established. Fourteen liver transplant recipients with recurrent hepatitis B infection (hepatitis B surface antigen [HBsAg] positive in serum; hepatitis on biopsy) were treated with IFN-alpha 2b (Intron A; Schering Inc, Kenilworth, NJ) 3 million units (MU) three times weekly for 23.5 weeks (median, range 4 to 41). The primary endpoint was loss of HBV DNA by the b-DNA assay (a virological response). Before treatment, all patients were HBV DNA positive and 9 were hepatitis B e antigen (HBeAg) positive. Pretreatment HBV DNA levels were 6,760 MEq/mL (median, range 2.0 to 11,888 MEq/mL). HBV DNA levels decreased significantly with treatment (P = .03). Four patients had a complete and sustained virological response. Virological responses did not consistently correlate with biochemical response because of concomitant hepatitis C. Two patients had a serological response; 1 lost HBeAg, another lost HBeAg and HBsAg. All responders remained HBV DNA negative in follow-up (mean, 32 months; range, 23 to 40), but 1 patient required retransplantation for cirrhosis. Of the nonresponders, 1 patient required retransplantation for chronic rejection, 3 required retransplantation for recurrent hepatitis B, 3 died with recurrent hepatitis B, and 3 are alive and remain HBV DNA positive. IFN-alpha can induce a sustained serological (14%) and virological response (29%) in liver transplant recipients with recurrent HBV infection.