Safety and efficacy of subcutaneous hepatitis B immunoglobulin after liver transplantation: an open single-arm prospective study.

Life-long hepatitis B immunoglobulin (HBIG) administration is a main component of prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver transplantation (LT). Long-term effects of HBIG treatment are known only for intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy of self-administered SC HBIG, 135 LT patients receiving a 48-week treatment were analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was <75 kg or ≥75 kg, respectively. Patients were switched from the monthly IV HBIG treatment to weekly SC HBIG 2-3 weeks after the last IV dosage. All patients were able to SC self-injection after a single training. The treatment was effective in maintaining trough anti-HBs levels >100 IU/L. No severe drug-related side effects occurred. Fifteen injection-site small hematomas and four cases of mild itch occurred. At the end of the study, anti-HBs median titer was 232 IU/L (115-566 IU/L) and 97.8% of patients had an anti-HBs level >150 IU/L. Due to high mean level of anti-HBs titers observed during this study, individualized treatment schedules should be further investigated. In conclusion, SC HBIG for long-term prophylaxis of post-LT HBV reinfection resulted safe, well accepted, and effective in maintaining adequate anti-HBs levels.

Telbivudine prophylaxis for hepatitis B virus recurrence after liver transplantation improves renal function.

INTRODUCTION: Renal impairment after liver transplantation represents an important issue in the management of transplantation patients, particularly when those subjects may need prophylaxis for fungal or viral infection. Herein we report our experience with 12 transplantation patients receiving telbivudine 600 mg/d while on the waiting list, followed by treatment for 18 months after liver transplantation, showing an improvement on their renal function during the follow-up period. METHODS: Our series consisted of men with hepatitis B virus (HBV)-related end-stage liver disease. The viral load decreased rapidly while on the waiting list once the patient was started on antiviral treatment. Those subjects were compared with 12 patients on lamivudine prophylaxis. All patients were evaluated for liver and renal function, immunosuppression trough levels, and creatine phosphokinase (CPK) before liver transplantation (T0) and at 3, 6, 12, and 18 months (T3, T6, T12, T18). RESULTS: All patients received a calcineurin inhibitor immunosuppression-based regimen. Creatinine clearance (Modification of Diet in Renal Disease) was 67 mL/min at T0, with a statistically significant improvement after month 6 compared with those on lamivudine and with the value at the beginning of the prophylaxis (Mann-Whitney U test P<.05). Neither CPK nor transaminase serum levels increased throughout the study period. Once HBV DNA was cleared while on the waiting list, it remained negative throughout the follow-up period. CONCLUSIONS: Telbivudine prophylaxis for HBV is safe and effective, without any significant deleterious effect on the liver; on the contrary, it seems to improve renal function after liver transplantation through 18 months. Further studies and larger series are warranted to confirm these findings.

Resistance to alpha interferon therapy in HCV chronic liver disease: role of hepatic fibrosis.

The response rate to interferon in HCV chronic liver disease is insufficient to date and the causes of this failure are not fully understood. Hepatic fibrosis hinders the blood-hepatocyte exchange of substances and we hypothesized that this process may also reduce the efficacy of interferon. Serum levels of connective tissue metabolites are related, to some extent, to the amount of extracellular matrix in the liver. Therefore, the usefulness was evaluated of serum tests of connective tissue metabolism compared to standard biochemical and histological parameters in predicting the probability of primary response to interferon. Sixty-eight patients with HCV chronic liver disease were treated with alpha-interferon for 1 year. At multivariate analysis time 0, the serum level of the P1 fragment of laminin was found to be the only factor independently associated with the response to treatment. As is well known, higher serum concentrations of the P1 fragment of laminin are associated with active basement membrane turnover and derangement of the hepatic structure. Therefore, this process seems to reduce the probability of response to interferon and, if confirmed, evaluation of serum the P1 fragment of laminin may be a useful test to predict the response to interferon and to define the therapeutic strategy, especially as far as the dose of interferon is concerned.