High post-transplant virological response in hepatitis C virus infected patients treated with pretransplant protease inhibitor-based triple therapy.

BACKGROUND & AIMS: Prevention of recurrent hepatitis C virus (HCV) following liver transplant (LT) with pre-LT antiviral therapy is limited by poor tolerability and efficacy. We aimed to evaluate the safety and efficacy of NS3/4A protease inhibitor (PI)-based triple therapy in patients awaiting LT. METHODS: Consecutive patients treated with triple therapy pre-LT from two centers were prospectively enrolled in an observational cohort. Overall 12 week sustained virological response (SVR12) was the primary outcome. Pre- and post-LT (pTVR) virological response rates and safety were secondary outcomes. RESULTS: Twenty-nine patients (mean age 57.9, 79% male, 66% prior non-responders) were treated with telaprevir (93%) or boceprevir-based (7%) triple therapy for a median (range) of 27 (3-50) weeks, including a pegylated-interferon and ribavirin lead-in in 18%. Median (range) MELD at treatment was 8 (6-16), 39% had hepatocellular carcinoma and all patients were Child-Turcotte-Pugh class A (62%) or B (38%). Twelve patients underwent LT, 75% with undetectable viral load. The overall SVR12 rate was 52%, including pre-LT SVR12 of 41% in patients who completed treatment and follow-up on the wait list and pTVR12 of 67% among transplanted patients. The pTVR12 rate was 89% among those patients with undetectable viral load at LT. Serious adverse events occurred in nine (31%) patients including one (3%) on-treatment death and eight (28%) hospitalizations. CONCLUSIONS: Overall SVR12 and pTVR12 rates are high among patients treated with PI-based triple therapy while awaiting LT, even in this difficult to treat population. However, caution is needed as early discontinuation and serious adverse events are common.

Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues.

Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence. Seven hundred thirty-eight patients underwent transplantation for HBV, and 354 (48.0%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs were the most frequent first site of HCC recurrence, and they were followed by the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence, and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P = 0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC, vascular invasion of the explanted tumor, and post-LT chemotherapy were associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001, respectively). Patients with HBV reinfection were 3.6 times more likely than patients without HBV to have HCC recurrence. These data suggest further study of attempts at LT for patients with HBV and HCC beyond the Milan criteria if their HBV is aggressively and successfully treated.

Multicenter review of liver transplant for hepatitis B-related liver disease: disparities in gender and ethnicity.

Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected.

Increased risk of colorectal polyps in patients with non-alcoholic fatty liver disease undergoing liver transplant evaluation.

BACKGROUND: Screening colonoscopy is a standard part of the liver transplant (LT) evaluation process. We aimed to evaluate the yield of screening colonoscopy and determine whether non-alcoholic fatty liver disease (NAFLD) was associated with an increased risk of colorectal neoplasia. METHODS: We retrospectively assessed all patients who completed LT evaluation at our center between 1/2008-12/2012. Patients <50 years old and those without records of screening colonoscopy, or with greater than average colon cancer risk were excluded. RESULTS: A total of 1,102 patients were evaluated, 591 met inclusion criteria and were analyzed. The mean age was 60 years, 67% were male, 12% had NAFLD and 88% had other forms of chronic liver disease. Overall, 42% of patients had a polyp found on colonoscopy: 23% with adenomas, 14% with hyperplastic polyps and with 1% inflammatory polyps. In the final multivariable model controlling for age, NAFLD [odds ratio (OR) 2.41, P=0.001] and a history of significant alcohol use (OR 1.69, P=0.004) were predictive of finding a polyp on colonoscopy. In addition, NAFLD (OR 1.95, P=0.02), significant alcohol use (OR 1.70, P=0.01) and CTP class C (OR 0.57, P=0.02) were associated with adenoma, controlling for age. CONCLUSIONS: Screening colonoscopy in patients awaiting LT yields a high rate of polyp (43%) and adenoma (22%) detection, perhaps preventing the accelerated progression to carcinoma that can occur in immunosuppressed post-LT patients. Patients with NAFLD may be at a ~2 fold higher risk of adenomas and should be carefully evaluated prior to LT.