Viral persistence after liver transplantation for hepatitis B virus: a cross-sectional study.

BACKGROUND: Prophylaxis to prevent recurrent HBV infection in liver transplant (LT) recipients has evolved over time, and we manage patients who receive lamivudine monoprophylaxis, lamivudine with HBV immunoglobulin (HBIg), and lamivudine and adefovir with HBIg. METHODS: Serum was examined with sensitive assays to detect the persistence of HBV, and to identify mutations that might confer resistance to the antiviral prophylaxis. Forty patients were studied, and sera were collected 20 days to 13.3 years after LT. RESULTS: Overall, HBV DNA was detected in serum of 67.5% of patients (8 of 10 of lamivudine monoprophylaxis patients, 15 of 24 of those receiving lamivudine and HBIg, and 4 of 6 of those receiving lamivudine, adefovir and HBIg). Thus, HBV infection persists for most of the patients despite successful prophylaxis after LT. Of those patients with detectable serum HBV DNA, three of eight of the lamivudine monoprophylaxis group had sequences associated with resistance to lamivudine (YMDD mutants), compared with only 1 of 15 of the lamivudine and HBIg cohort. Three of the lamivudine and HBIg cohort had the I126A Hepatitis B surface antigen escape variant. In those serum HBV DNA-positive patients who were receiving lamivudine, adefovir, and HBIg, only one of four had YMDD mutant, and none had Hepatitis B surface antigen escape variants. None of the 40 patients suffered clinical HBV recurrence. CONCLUSIONS: Our observations imply that the selection of resistant virus may be essential, but is not sufficient to cause overt failure of prophylaxis with development of clinical disease. It seems likely that the patients' immune response contributes, at least partially, to the long-term control of infection in these patients.

Tacrolimus and cyclosporin doses and blood levels in hepatitis C and alcoholic liver disease patients after liver transplantation.

Hepatitis C virus (HCV)-induced cirrhosis is the most common indication for liver transplantation (LT). However, graft reinfection is nearly universal. The choice of immunosuppression, including the calcineurin inhibitor (CNI), may have some effect on severity of recurrence and graft survival. In addition, HCV recurrence may have some impact on metabolism of immunosuppressive drugs. In this retrospective study, we examined the dose and blood levels of tacrolimus (TAC) and cyclosporin A (CYA) in HCV patients consecutively undergoing transplantation (TAC, n = 44; CYA, n = 60) and surviving 12 months post-LT. In addition, we examined the CNI dose and blood levels in an age- and gender-matched comparison group of patients who were transplanted for alcoholic liver disease (ALD) (TAC, n = 44; CYA, n = 47). During the 12-month period of observation, TAC levels were significantly higher for HCV than for ALD patients (P = 0.002). The dose of TAC decreased over time for both HCV and ALD patients (P < 0.001), but the reduction was greater for HCV patients (P = 0.03). CYA dose decreased over time for both groups (P < 0.001) but a greater reduction was observed for the HCV group (P = 0.007). For both HCV and ALD patients, CYA levels decreased over time (P < 0.001) but there was no significant difference between HCV and ALD patients. Thus, to maintain comparable blood levels, a greater reduction of dose was required for HCV than for ALD patients. In conclusion, our observations demonstrate a likely effect of HCV infection on CNI metabolism, an effect that is not clearly due to graft damage. Physicians need to be alert to this interaction and to the need to respond quickly to changes in CNI levels that may be associated with HCV infection and with HCV clearance during antiviral therapy.

Quality of life after liver transplantation for hepatitis C infection.

INTRODUCTION: Transplantation is a life-saving option for patients with liver disease. However, recovery is variable. Impairments in physical health, emotional wellbeing and quality of life are reported. Quality of life may be worse after transplantation for hepatitis C virus (HCV) infection. OBJECTIVE: To identify factors that could impact on quality of life after liver transplantation for HCV infection. METHODS: A qualitative design was used. Data were collected by in-depth interview. Colaizzi's framework for data analysis was used. RESULTS: Varying levels of physical and psychological disability persist for many years after liver transplantation. Participants described living productive and meaningful lives. Many reported a more positive outlook on life since transplantation. Many felt stigmatised by the association of liver disease with alcohol/drug misuse. Participants described the uncertainty of life after transplantation. While all expressed gratitude to the donor, emotional responses to the donation varied. CONCLUSIONS: Transplant recipients exchange one health state for another. Pre-transplant preparation should encourage realistic expectations of life after transplantation. Before transplantation, potential recipients should be given an opportunity to discuss the donation process. This may reduce the burden of emotional debt experienced by some recipients. Feelings of stigma and future uncertainty may be worse for transplant recipients with HCV. A qualitative approach can provide deeper insight into issues affecting quality of life after transplantation for HCV, and explain some of the ambiguous and contradictory findings of previous quantitative studies.

Results of combination treatment with pegylated interferon and ribavirin in cirrhotic patients with hepatitis C infection.

BACKGROUND: The treatment of hepatitis C patients with advanced cirrhotic liver disease remains challenging and data on the outcome of treatment for this patient group is limited. RESULTS: Between September 2000 and August 2004, 61 cirrhotic patients started treatment with pegylated interferon and ribavirin (42 male, age range 29-69 years, 26 Asian). Forty-three (70%) patients were serum hepatitis C virus (HCV) RNA negative at the end of treatment and 24 (39%) achieved a sustained virological response (SVR). SVR was achieved for 35% (6/17) of patients with genotype 1, and for 39% (16/41) with genotype 3. Caucasians with genotype 3 demonstrated a higher cure rate (SVR 10/18 = 56%) than Asians (SVR 6/24 = 25%). Failure to achieve SVR was associated with lower platelet count, neutrophil count and albumin at baseline. Twenty patients suffered clinical or laboratory decompensation, five patients required hospitalization, and two patients died. Patients who experienced hepatic decompensation were older and had baseline characteristics associated with more advanced liver disease. CONCLUSION: The treatment of patients with advanced HCV is challenging, although many treated patients achieve SVR. Significant toxicity is experienced and there is treatment-related mortality. This balance of efficacy and toxicity needs to be considered before commencing treatment.