The Reliability of Fibro-test in Staging Orthotopic Liver Transplant Recipients with Recurrent Hepatitis C.

Background and Aims: Liver biopsy remains the gold standard for staging of chronic liver disease following orthotopic liver transplantation. Noninvasive assessment of fibrosis with Fibro-test (FT) is well-studied in immunocompetent populations with chronic hepatitis C virus infection. The aim of this study is to investigate the diagnostic value of FT in the assessment of hepatic fibrosis in the allografts of liver transplant recipients with evidence of recurrent hepatitis C. Methods: We retrospectively compared liver biopsies and FT performed within a median of 1 month of each other in orthotopic liver transplantation recipients with recurrent hepatitis C. Results: The study population comprised 22 patients, most of them male (19/22), and with median age of 62 years. For all patients, there was at least a one-stage difference in fibrosis as assessed by liver biopsy compared to FT, while for the majority (16/22) there was at least a two-stage difference. The absence of correlation between the two modalities was statistically demonstrated (Mann-Whitney U test, p = 0.01). In detecting significant fibrosis (a METAVIR stage of F2 and above), an FT cut-off of 0.5 showed moderate sensitivity (77%) and negative predictive value (80%), but suboptimal specificity (61%) and positive predictive value (58%). Conclusions: In post-transplant patients with recurrent hepatitis C, FT appears to be inaccurately assessing the degree of allograft fibrosis, therefore limiting its reliability as a staging tool.

The safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in the treatment of orthotopic liver transplant recipients with recurrent hepatitis C: real-world data.

BACKGROUND: Recurrent hepatitis C (RHC) in orthotopic liver transplantation (OLT) population is associated with accelerated rates of fibrosis, low efficacy and decreased tolerability with traditional therapies. AIM: The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir (LED/SOF) with or without ribavirin (RBV) in OLT patients with RHC. PATIENTS AND METHODS: Patients at least 3 months post-OLT and with documented RHC were treated with LED/SOF with or without RBV for either 12 or 24 weeks. End-of-treatment and sustained virological response 12 weeks after the completion of treatment were documented. Patients were closely monitored for treatment-related adverse effects and the potential need for adjustment in their immunosuppression. RESULTS: Seventy-one patients were included in the study. Median age was 62 years. Median time from OLT was 55 months. Twenty-six (36.6%) patients were treatment-naive and 45 (63.4%) had previously failed interferon-based therapies. The majority of patients (57.7%) had stage F0-F2 fibrosis. Sixty-seven (94.3%) patients completed 12 weeks of LED/SOF with RBV, three patients completed 12 or 24 weeks of LED/SOF without RBV, and one patient completed only 8 weeks of LED/SOF without RBV owing to severe allograft dysfunction. Sustained virological response was near universal in our cohort (98.5%) regardless of genotype, fibrosis stage, and regimen or treatment duration. Most commonly reported side effects were malaise and gastrointestinal upset. No patient required adjustment in immunosuppression and no episodes of rejection were documented during treatment. CONCLUSION: The combination of LED/SOF with RBV for 12 weeks or LED/SOF for 24 weeks is very effective and safe in treating OLT recipients with RHC.

Prophylaxis Among Hepatitis B Core Antibody-positive Deceased-donor Liver Transplant Recipients: Hepatitis B Immunoglobulin Plus Oral Antiviral Agents Versus Antiviral Agents Alone: A Single-center Experience.

OBJECTIVES: Hepatitis B core antibody immunoglobulin G seropositivity is evidence of past exposure to hepatitis B virus. Donor or recipient hepatitis B core antibody positivity may pose a risk of reactivation, especially early after liver transplant. Although most centers advocate using antiviral agents plus hepatitis B immunoglobulin, some have recently relied on antivirals only as prophylaxis after liver transplant. Here, we retrospectively investigated patient survival in hepatitis B core antibody-positive recipients, comparing those treated with antivirals plus hepatitis B immunoglobulin versus antivirals alone. MATERIALS AND METHODS: After Internal Review Board approval, we reviewed medical records of deceased-donor liver transplant recipients between 1995 and 2013. Demographic characteristics, transplant indication, hepatitis B core antibody status, time to death, and type of posttransplant prophylaxis were recorded. We also recorded whether donors showed hepatitis B core antibody positivity. Patients who died within 30 days of liver transplant were excluded. RESULTS: There were 148 hepatitis B core antibody-positive recipients. Prophylaxis was given to 75 recipients after transplant: 8 (5%) received hepatitis B immunoglobulin, 22 (15%) received antivirals, and 45 (30%) received the combination. There were 34 deaths: 3 (38%) in hepatitis B immunoglobulin only, 3 (14%) in antiviral only, 8 (18%) in the combination, and 20 (27%) in no prophylaxis groups. One- and 5-year survival rates were similar for binary comparisons among prophylaxis groups (P > .05). CONCLUSIONS: Preliminary results support the current practice of using hepatitis B immunoglobulin plus antivirals for prophylaxis after liver transplant. The similar survival benefit with the combination versus antiviral agents alone suggests equal effectivity for prophylaxis posttransplant. However, a clear benefit of antivirals was not evident in our analysis. Future larger prospective studies are warranted to identify potential benefits of using antivirals alone as prophylaxis after liver transplant and to further clarify their role as the sole prophylactic regimen.

The predictors of post-transplant coronary events among liver transplant recipients.

BACKGROUND/PURPOSE: Cardiac morbidities can occur during the peri- and post-liver transplant (LT) period, affecting the long-term survival. The purpose of this study was to identify the potential factors that predict a coronary event post-transplantation. METHODS: Medical records of patients who underwent liver transplantation at Johns Hopkins Hospital between 2009 and 2013 were retrospectively reviewed. We looked at pre-liver transplant cardiac risk factors and the diagnostic tests utilized for coronary artery disease screening. Patients with and without post-liver transplant coronary events were compared. RESULTS: There were a total of 146 patients with a mean age at LT of 55.3 years. The prevalence of hypertension, tobacco use and diabetes within the patient population was 61.6 % (n = 90), 39 % (n = 57) and 37.6 % (n = 55), respectively. There were 29 deaths and 30 coronary events over a median follow-up period of 1.75 years. Age at the time of liver transplant was predictive of coronary event (OR 1.11, CI 1.01-1.20). The 1-year survival in patients with a coronary event was 47 versus 94 % in patients without a coronary event. The combined use of a dobutamine stress echocardiogram and coronary artery calcium score predicted a coronary event with a sensitivity of 62.5 % and specificity of 66.7 %. CONCLUSION: In conclusion, LT recipients with cardiac events had limited survival as compared to the cohort without coronary events. Identification of such patients with noninvasive screening may provide a practical alternative to an invasive cardiac workup. Further improvement in screening strategies may minimize the liver transplant cardiac morbidity.

Greater Biosynthetic Liver Dysfunction in Primary Sclerosing Cholangitis Suggests Co-existent or Impending Cholangiocarcinoma.

Background and Aim : Patients with primary sclerosing cholangitis (PSC) who develop cholangiocarcinoma (CCA) have a median survival of less than 6 months. In half of cases, PSC and CCA will be diagnosed either concurrently or within a year of one another. The aim of the present study is to demonstrate that the degree of biochemical liver dysfunction is associated with concomitant or impending CCA. Methods : We did a chart review of patients diagnosed with PSC and CCA up to 18 months from presentation ("CCA" group) as well as patients with PSC that underwent transplantation with no sign of CCA in their explanted liver ("nCCA" group). Along with demographic data and follow-up length, we recorded their presenting liver function tests, including alanine and aspartate aminotransferases (ALT, AST), total bilirubin (TBil), alkaline phosphatase (ALP), international normalization ratio (INR), and serum Ca 19-9 levels. Differences between mean values of the two groups were analyzed with a student's t-test. Results : Twenty-four patients were included. The "CCA" group consisted of eight patients, and the "non-CCA" group had 16 patients. There was no significant difference between the two groups in their presenting values of ALT, ALP, or serum Ca 19-9. However, the "CCA" group had significantly higher levels of AST, TBil, and INR. Conclusion : Patients with PSC and concurrent or impending CCA appear to exhibit significantly greater biochemical liver dysfunction than those who do not develop CCA. Therefore, newly-diagnosed PSC patients presenting with these findings may warrant more rigorous evaluation.

Effect of prior hepatitis B virus exposure on long-term risk of liver-related events after liver transplantation.

OBJECTIVE: To characterize the risk of liver-related events and death in hepatitis B virus (HBV)-exposed liver transplantation (LT) recipients. METHODS: Retrospective review was performed in all adults who underwent LT between January 1995 through December 2010 at the Johns Hopkins Hospital. Recipients with graft failure or death within 14 d of LT or missing HBV status were excluded, leaving 575 individuals for analysis. Patients were classified according to HBV exposure status: Unexposed, Resolved HBV, Chronic HBV, or hepatitis B core antibody (anti-HBc) seropositive liver donor. RESULTS: Compared with HBV-unexposed patients, the relative hazard of combined liver-related events (rejection, cirrhosis, re-transplantation) and death after LT was not increased in patients with a baseline history of resolved HBV infection or chronic hepatitis B. Using anti-HBc seropositive donors also did not increase the risk of liver-related events, death, or composite events (all p ≥ 0.05). However, hepatitis C was associated with liver-related events [adjusted hazard ratio (aHR), 1.59; 95% confidence interval (CI), 1.00-2.52], and blacks had a higher risk of death (aHR, 1.50; 95% CI, 1.01-2.22). CONCLUSION: LT of patients with prior HBV exposure or use of anti-HBc seropositive donors is not associated with increased risk of liver-related events or death.

Trends in pre-liver transplant screening for cholangiocarcinoma among patients with primary sclerosing cholangitis.

BACKGROUND: Cholangiocarcinoma (CCA) is the most common hepatobiliary malignancy complicating primary sclerosing cholangitis (PSC). Unfortunately, timely diagnosis of CCA in PSC patients remains challenging. AIM: To investigate the strategies among liver centers regarding pre-transplant screening for CCA in patients with PSC. METHODS: An online survey was returned from 46 US transplant centers, inquiring on the frequency of screening, the use of specific tests, or tactical approaches to high-grade dysplasia (HGD) or CCA. RESULTS: Most centers screen their PSC patients for CCA prior to orthotopic liver transplantation (OLT) (89%). Serum carbohydrate antigen 19-9 and magnetic resonance cholangiopancreatography are first-line screening tools (93 and 84% respectively). Endoscopic retrograde cholangiopancreatography with biliary brushings is routinely performed in only 30% of the centers. In the case of HGD, 61% would choose close monitoring. In the event of non-resectable CCA, 37% have an OLT protocol, 33% resort to palliative treatment and the remaining 30% make an outside referral. Finally, half the participating centers perform CCA surveillance among their listed PSC patients every 6 months. CONCLUSION: Screening for CCA among PSC patients prior to OLT varies greatly among centers. Serum carbohydrate antigen 19-9 and magnetic resonance cholangiopancreatography are widely used. HGD warrants surveillance rather than intervention among most experts. Protocolized chemoradiation followed by OLT has yet to become a widely accepted approach. The very poor survival of PSC patients who develop CCA underlines the importance of an effective and universally accepted screening process that will aid in its earlier detection.

Efficacy and safety of interferon-based therapy in the treatment of adult thalassemic patients with chronic hepatitis C: a 12 years audit.

BACKGROUND: HCV infection and transfusional iron overload in Thalassemic patients may result in liver disease. HCV treatment in Thalassemia has raised safety concerns. AIM: Estimate effectiveness and tolerability of interferon-based therapy in HCV-infected Thalassemic patients. MATERIAL AND METHODS: Over a 12-year period, consecutive patients with ß Thalassemia major (TM) and chronic hepatitis C received treatment. Liver biopsy, HCV-RNA and genotyping were performed beforehand. Sustained virological response (SVR) was defined as negative HCV-RNA 6 months post-treatment. Forty eight patients (26 M-22 F, mean age 39.8) were enrolled. Twenty nine patients were treated with conventional interferon alpha (IFNa) for 48 weeks (group A). Nineteen patients (10 naïve-9 previously IFNa experienced) received pegylated interferon (PEGIFN) (group B). RESULTS: HCV-1 was found in 44%, HCV-2 in 14%, HCV-3 in 23% and HCV-4 in 19%. Group A: ten patients (38.5%) achieved SVR, 2 (7.5%) relapsed and 17 (54%) were non responders. Group B: five (28%) achieved SVR, 8 (44%) relapsed and 6 (28%) never responded. High HCV-RNA levels, genotype 1 and advanced liver fibrosis were independently associated with no response. Four patients (3 treated with IFNα, 1 with PEG-IFN) had to discontinue treatment due to complications. CONCLUSIONS: The response rate of IFN monotherapy in multi-transfused, HCV-infected Thalassemic patients is not inferior to that in non-multitransfused patients. IFNa administration is well-tolerated and should be recommended as initial treatment schedule in this setting.