Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma.

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

Donor factors similarly impact survival outcome after liver transplantation in hepatocellular carcinoma and non-hepatocellular carcinoma patients.

BACKGROUND: Many have advocated the preferential use of high risk allografts for hepatocellular carcinoma patients undergoing liver transplantation. Hepatocellular carcinoma (HCC) patients tend to have relatively preserved liver function, and their outcome is felt to be driven largely by tumor-related factors. AIM: The aim of this study was to compare the relative importance of donor versus recipient factors on post-orthotopic liver transplantation survival among HCC and non-HCC recipients. METHODS: The study group included Scientific Registry of Transplant Recipients data on adult recipients of deceased donor liver transplants from February 2002 through December 2008. Recipients were classified as HCC based on MELD exception applications and were compared to all other recipients. Predictors of post-LT survival were identified by Cox regression. To test whether donor factors have less impact on survival in HCC patients, interaction terms were created between HCC diagnosis and donor factors. RESULTS: Of the 40,212 DDLTs during the study period, 29,020 (72 %) met study criteria. A total of 7,786 (27 %)were transplanted with a diagnosis of HCC. The mean donor risk index was 1.5 in both cohorts. The 1-/5-year survival was 88 %/68 % and 87 %/74 % among HCC and non-HCC recipients, respectively (p\0.0001). On multivariate analysis, there was no statistically significant interaction between HCC diagnosis and DRI (HR 0.94,p = 0.317). Likewise, no interaction was seen between HCC diagnosis and individual donor factors. In both groups, donor and recipient factors carried similar weight in determining post-LT survival. CONCLUSIONS: Contrary to previous assumptions, donor factors play a similar role in determining survival post-LT among HCC patients and non-HCC patients.

Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000.

BACKGROUND: The incidence of cholangiocarcinoma (CCA) continues to rise. Orthotopic liver transplantation (OLT) can be used for selected patients with localized but unresectable hilar CCA. Although initial post-OLT survival rates were poor, outcomes after introduction of the Mayo Clinic protocol have been more promising and there has been increased interest in OLT for CCA nationally. AIMS: The aim of this study is to determine post-transplant survival and prognostic factors for patients undergoing OLT for CCA. METHODS: A retrospective analysis of all patients with CCA listed nationwide for OLT between October 1987 and May 2008 was performed using the Scientific Registry of Transplant Recipients database. Survival curves were generated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Of 595 patients with CCA listed for OLT, 359 (60.3 %) underwent OLT. Median age at OLT was 49 years, 66 % were male and 91 % were Caucasian. The median follow-up time was 2 years. There has been an increasing number of liver transplants performed for CCA since 2000. The 1- and 5-year probability of survival was 85.8 and 51.4 %, respectively. On multivariate analysis, significant prognostic factors for decreased post-OLT survival included transplant before 2000 (HR 11.25, 95 % CI 1.28-98.7) and acute cellular rejection (HR 5.64, 95 % CI 1.14-27.8). CONCLUSIONS: Survival after transplant for CCA has improved over time, and OLT is being used more frequently in the treatment of CCA. Significant predictors of post-OLT survival include a history of acute rejection and date of transplant in relation to the publication of Mayo protocol results.

Outcomes of liver transplantation for porto-pulmonary hypertension in model for end-stage liver disease era.

UNLABELLED: Porto-pulmonary hypertension (POPH), once considered an absolute contraindication for liver transplantation (LT), has become a more accepted indication because of the evolution of treatment with prostacyclin analogues, phosphodiesterase inhibitors and endothelin receptor antagonists. An exception model for end stage liver disease (MELD) score of 22 is assigned to candidates with documentation of effective treatment. We examined the post-transplant outcomes of patients who received LT for POPH with exception. METHODS: Scientific Registry of Transplant Recipients data on 34,318 adult (≥ 18 years) deceased donor LT recipients transplanted between March 1, 2002 and August 31, 2010 were reviewed. The diagnosis of POPH was ascertained from MELD exception forms. Patients were followed from the time of transplant until the earlier occurrence of death or end of the follow-up period. Cox regression was used to evaluate the predictors of post-LT mortality and graft failure. RESULTS: During the study period, 34,318 patients received deceased donor LT. Seventy eight out of 34,318 patients were transplanted for POPH with MELD exception. The 1-year adjusted risks of patient death and graft failure for patients transplanted under exception rules for POPH were significantly higher than with POPH adult recipients who did not receive exception points (death:hazard ratio [HR] = 2.25, p = 0.005 and graft failure HR = 1.96, p = 0.012). CONCLUSIONS: This study of national data suggests that treated POPH continues to be associated with inferior early post-transplant outcomes.

The educational impact of the Specialty Care Access Network-Extension of Community Healthcare Outcomes program.

BACKGROUND: With the aging hepatitis C cohort and increasing prevalence of fatty liver disease, the burden on primary care providers (PCPs) to care for patients with liver disease is growing. In response, the Veterans Administration implemented initiatives for primary care-specialty referral to increase PCP competency in complex disease management. The Specialty Care Access Network-Extension of Community Healthcare Outcomes (SCAN-ECHO) program initiative was designed to transfer subspecialty knowledge to PCPs through case-based distance learning combined with real-time consultation. There is limited information regarding the initiative's ability to engage PCPs to learn and influence their practice. MATERIALS AND METHODS: We surveyed PCPs to determine the factors that led to their participation in this program and the educational impact of participation. RESULTS: Of 51 potential participants, 24 responded to an anonymous survey. More than 75% of respondents participated more than one time in a SCAN-ECHO clinic. Providers were motivated to participate by a desire to learn more about liver disease, to apply the knowledge gained to future patients, and to save their patients time traveling to another center for specialty consultation. Seventy-one percent responded that the didactic component and case-based discussion were equally important. It is important that participation changed clinical practice: 75% of providers indicated they had personally discussed the information they learned from the case presentations with their colleague(s), and 42% indicated they helped a colleague care for their patient with the knowledge learned during discussions of other participants' cases. CONCLUSIONS: This study shows that the SCAN-ECHO videoconferencing program between PCPs and specialists can educate providers in the delivery of specialty care from a distance and potentially improve healthcare delivery.

Portopulmonary Hypertension: A Survey of Practice Patterns and Provider Attitudes.

BACKGROUND: The role of liver transplantation (LT) in the management of portopulmonary hypertension (POPH) is poorly understood. The aim of this study was to better understand provider attitudes and practice patterns regarding the management of patients with POPH and to assess the concordance between clinical practice and current guidelines. METHODS: We performed a multicenter survey study of hepatologists and pulmonary hypertension (PH) physicians at US LT centers that performed >50 transplants per year. Survey responses are summarized as number (%). Associations were assessed using a Wilcoxon-rank sum, chi-square, or Fisher exact test, as appropriate. RESULTS: Seventy-four providers from 35 centers were included. There was marked variability regarding screening practices, management, and attitudes. Forty-two percent responded that POPH nearly always or often improves with LT, and 15.5% reported that POPH rarely or never improves. In contrast to current guidelines, 50.7% agreed that treated POPH should be an indication for LT in patients with compensated cirrhosis. Hepatologists were more likely than PH physicians to agree that POPH should be an indication for LT (P = 0.02). Forty-nine percent of respondents thought that the current POPH Model for End-stage Liver Disease exception criteria should be modified, and management of patients with an elevated mean pulmonary arterial pressure and normal pulmonary vascular resistance differed from current policies. CONCLUSIONS: There is marked variability in provider attitudes and practice patterns regarding the management of POPH. This study highlights the need for prospective studies to inform practice and for improved implementation of practice guidelines in order to standardize care.

Predictors of Waitlist Mortality in Portopulmonary Hypertension.

BACKGROUND: The current Organ Procurement Transplantation Network policy grants Model for End-Stage Liver Disease (MELD) exception points to patients with portopulmonary hypertension (POPH), but potentially important factors, such as severity of liver disease and pulmonary hypertension, are not included in the exception score, and may affect survival. The purpose of this study was to identify significant predictors of waitlist mortality in patients with POPH. METHODS: We performed a retrospective cohort study of patients in the Organ Procurement and Transplantation Network database with hemodynamics consistent with POPH (defined as mean pulmonary arterial pressure >25 mm Hg and pulmonary vascular resistance [PVR] ≥240 dynes·s·cm) who were approved for a POPH MELD exception between 2006 and 2014. Using a Cox proportional hazards model, we identified predictors of waitlist mortality (or removal for clinical deterioration). RESULTS: One hundred ninety adults were included. Age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.08; P = 0.0499), initial native MELD score (HR, 1.11; 95% CI, 1.05-1.17; P < 0.001), and initial PVR (HR, 1.12 per 100 dynes·s·cm; 95% CI, 1.02-1.23; P = 0.02) were the only significant univariate predictors of waitlist mortality and remained significant predictors in a multivariate model, which had a c-statistic of 0.71. PVR and mean pulmonary arterial pressure were not significant predictors of posttransplant mortality. CONCLUSIONS: Both the severity of liver disease and POPH (as assessed by MELD and PVR, respectively) were significantly associated with waitlist, but not posttransplant, mortality in patients with approved MELD exceptions for POPH. Both factors should potentially be included in the POPH MELD exception score to more accurately reflect waitlist mortality risk.

Diagnosis and management of hereditary hemochromatosis.

Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis.