Review article: the treatment of hepatitis C virus recurrence after liver transplantation.

BACKGROUND: Recurrent hepatitis C represents a major challenge for the liver transplant community. Given the potentially significant impact that hepatitis C recurrence has on graft and patient survival, several treatment strategies have been utilized to prevent/slow the progression to hepatitis C-related graft failure. AIM: To review the efficacy and applicability of treatment strategies for managing recurrent hepatitis C. METHODS: Search of MEDLINE (1990 to December 2006) and national meeting abstracts. Search terms included hepatitis C, liver transplantation, treatment, sustained virological response (SVR), and end of treatment virological response. An emphasis was placed on randomized trials. RESULTS: The largest study of treatment prior to liver transplantation (n = 124) achieved SVR in 24%. Eight randomized trials (n = 383) examined the efficacy of preemptive therapy with SVR ranging from 0-33%. Eligibility for treatment was low and dose reduction common. Four randomized trials (n = 245; all abstracts) have reported SVR from 33-42% for treating those with histological evidence of recurrent disease. CONCLUSIONS: Therapies for treating hepatitis C recurrence have limited applicability and tolerability, and they have a low SVR. Based on available results, preemptive therapy is not recommended. Pegylated interferon and ribavirin is currently the preferred choice for treating established recurrence. There is an urgent need for safer and more effective anti-viral therapy in this situation.

Changes in international normalized ratio (INR) and model for endstage liver disease (MELD) based on selection of clinical laboratory.

Priority for liver transplantation is based on the Model for Endstage Liver Disease (MELD) score, a mathematical function which includes international normalized ratio (INR). We present an analysis to determine the lab-to-lab variation in INR at 14 clinical laboratories across the United States. We performed a survey to identify representative clinical laboratories across the United States, where INR was measured in the determination of MELD score. Five 'standard' samples for INR were formulated and were sent to the 14 clinical laboratories to determine variation in INR and MELD score. Among the 14 clinical laboratories, the range in INR for the five samples was: sample 1 (1.2-2.0), sample 2 (1.4-2.5), sample 3 (1.7-3.4), sample 4 (1.9-3.7) and sample 5 (2.4-5.1). The range in calculated MELD score was: sample 1 (8-14), sample 2 (10-17), sample 3 (12-20), sample 4 (14-21) and sample 5 (16-25). The selection of the clinical laboratory used to determine INR may result in substantial changes in MELD score independent of severity-of-illness. These data suggest that further review of interlaboratory variation in MELD should be undertaken because of the potential impact on prioritization for liver transplantation.