Lamivudine monoprophylaxis for liver transplant recipients with non-replicating hepatitis B virus infection.

BACKGROUND: The aim of this study was to evaluate the efficacy of lamivudine (LAM) monoprophylaxis for patients with non-replicating hepatitis B virus (HBV) infection at orthotopic liver transplantation (OLT). METHODS: Among 128 liver recipients with HBV infection between 1994 and 2004 transplanted at our institution, 60 had non-replicating HBV infection at the time of OLT. Of those, 26 patients received LAM prophylaxis (monoprophylaxis group) and 34 patients received LAM and hepatitis B immunoglobulin (HBIG) prophylaxis (combination group) after OLT. RESULTS: Median follow-up after OLT was 67 and 54 months, for monoprophylaxis and combination groups respectively. One and five yr patient/graft survival were 96/85% and 96/80% in monoprophylaxis group, and 85/79% and 67/55% in combination group. HBV DNA was re-detected or increased >10(5) IU/mL in four patients (15%) at 20-29 month in monoprophylaxis group and six (18%) at 4-35 months in combination group. Recurrent hepatitis was seen in two patients (8%) at 27 and 45 months and monoprophylaxis group and three (9%) at 21-35 months in combination group. The rate of recurrence was not statistically different between two groups. CONCLUSION: LAM monoprophylaxis seemed to be effective for OLT recipients with HBV infection who had non-replicating HBV at transplantation. HBIG administration may play a less valuable role in preventing HBV recurrence in this group of patients.

Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.

Endoscopic sinus surgery in patients with chronic hepatic failure awaiting liver transplant.

BACKGROUND: Because of the need for posttransplant immunosuppression, patients with chronic liver failure requiring transplantation must be free of infection to maintain an active status on the transplant list. These patients present significant surgical risks due to coagulopathy. Here, we present our experience with endoscopic sinus surgery for medically refractory sinusitis in this patient population. METHODS: We created a prospective case series of seven patients undergoing 10 surgeries. RESULTS: All patients were given preoperative blood product infusions. Operative blood loss ranged from 150 to 1500 cc with an average of 495 cc. Two cases had to be stopped before completion because of bleeding obscuring visualization. The two cases with the greatest blood loss were in patients with the most severe liver disease (highest mathematical model for end-stage liver disease scores), lowest albumin, and most extensive sinus disease. All patients were returned to active status on the liver transplant list and four patients have undergone liver transplantation. CONCLUSION: Patients with chronic hepatic disease awaiting liver transplant can be treated successfully with endoscopic sinus surgery, but significant perioperative bleeding may not be avoidable. Preoperative use of fresh frozen plasma, platelets, and sometimes albumin are necessary, and postoperative blood products may be required with more significant sinus and liver disease. NovoSeven (recombinant factor Vlla) was used on two occasions in one patient, with maximal correction of the patient's coagulopathy. Patients should be counseled on the possible need for additional procedures to adequately clear disease.

Lack of seronegative hepatitis C virus infections in patients with chronic renal failure.

BACKGROUND: Recent reports have indicated that serologic testing for hepatitis C virus (HCV) in patients with chronic renal failure may be inadequate to detect infections in this patient population. METHODS: We prospectively tested 258 patients with end-stage renal disease who were referred for evaluation for renal transplantation for anti-HCV using a second-generation enzyme immunoassay (EIA) and a second-generation qualitative reverse-transcriptase polymerase chain reaction (RT-PCR). We confirmed all positive EIAs with a third-generation recombinant immunoblot assay and genotyped RT-PCR-positive specimens. RESULTS: We found that 22 patients (8.5%) had serological evidence of HCV infection. Nineteen (86%) of the antibody-positive patients were viremic (HCV RNA positive). All but 1 of the patients was infected with HCV genotype 1. None of the 233 HCV antibody-negative patients were shown to be viremic by RT-PCR. CONCLUSIONS: No additional HCV cases were detected by screening all patients for HCV RNA by RT-PCR. However, RT-PCR is a valuable adjunct to serology in antibody-positive patients to distinguish resolved from active infections.