Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20‐year experience

Dumitra, Sinziana; Alabbad, Salleh I.; Barkun, Jeffrey; Dumitra, Teodora; Coutsinos, Dimitrios; Metrakos, Peter; Hassanain, Mazen; Paraskevas, Steven; Chaudhury, Prosanto

doi:10.1111/hpb.12041

Cited by 17 publications

(10 citation statements)

References 37 publications

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“…Even after adjusting for multiple potential contributing factors in the multivariate model, the survival disadvantage associated with HCV and HCC persisted. Lower post‐LT survival among patients with HCV has been attributed to the high rate of HCV recurrence among this cohort . However, this survival difference appears to be limited to patients without HCC, as our subanalyses of patients with HCC demonstrated no significant difference in post‐LT five‐yr patient or graft survivals by etiology of liver disease.…”

Section: Discussionmentioning

confidence: 62%

Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data

Wong

Chou

Bonham

et al. 2014

Clinical Transplantation

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There is an increasing trend of patients with hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease undergoing liver transplantation in the US. Our study utilized data from the 2002 to 2012 United Network for Organ Sharing registry to evaluate model for end-stage liver disease era trends in US liver transplantations focused on patients with non-alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease (ALD), and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan-Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index (BMI), and had higher prevalence of diabetes and cardiac disease. However, overall long-term survival was significantly higher in patients with NASH and ALD (p < 0.001). Compared to HCV, patients with NASH had significantly higher post-transplantation survival (HR 0.69, 95% CI 0.63-0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69-0.83). Despite having higher BMI and higher prevalence of diabetes and cardiac disease, patients with NASH had better post-liver transplantation survival compared to patients with HCV or HCC. Patients with ALD also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation.

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Section: Discussionmentioning

confidence: 62%

Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data

Wong

Chou

Bonham

et al. 2014

Clinical Transplantation

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“…HCV infection predicted only shorter post‐LT survival for non‐HCC patients. Prior studies noted the same lack of an association between HCV and post‐LT outcomes in patients undergoing transplantation for HCC . We theorize that HCV reinfection after LT primarily imparts a post‐LT mortality risk by increasing the risk of recurrent cirrhosis rather than recurrent HCC.…”

Section: Discussionmentioning

confidence: 74%

“…Prior studies noted the same lack of an association between HCV and post-LT outcomes in patients undergoing transplantation for HCC. [40][41][42] We theorize that HCV reinfection after LT primarily imparts a post-LT mortality risk by increasing the risk of recurrent cirrhosis rather than recurrent HCC. Because recurrent cirrhosis and recurrent HCC are competing risks in patients undergoing transplantation with both HCV and HCC (HCC recurrence does not require HCV-related graft fibrosis), it follows that HCV would be a weaker predictor of post-LT survival in patients with both HCC and HCV versus HCV alone.…”

Section: Discussionmentioning

confidence: 99%

Waiting time predicts survival after liver transplantation for hepatocellular carcinoma: A cohort study using the United Network for Organ Sharing registry

et al. 2014

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Recipients of liver transplantation (LT) for hepatocellular carcinoma (HCC) have an 8% to 20% risk of HCC recurrence. Single-center studies suggest that a period of waiting after HCC therapy may facilitate the selection of patients at low risk for post-LT HCC recurrence and mortality. We evaluated whether a longer waiting time after Model for End-Stage Liver Disease (MELD) prioritization for HCC predicts longer post-LT survival. From the United Network for Organ Sharing registry, we selected 2 groups registered for LT between March 2005 and March 2009: (1) HCC patients receiving MELD prioritization and (2) non-HCC patients. Patients were stratified by their MELD status at LT (a marker of time on the wait list after HCC MELD prioritization) and were followed from LT until death or censoring through October 2012. By comparing post-LT survival to intention-to-treat (ITT) survival from registration, we assessed predictors of post-LT survival and estimated the benefit of LT. The median MELD scores at LT were 22 (HCC) and 24 (non-HCC). A higher MELD score at LT was independently associated with lower post-LT mortality in the HCC group [hazard ratio (HR) 5 0.84, 95% confidence interval (CI) 5 0.73-0.98] and higher post-LT mortality in the non-HCC group (HR 5 1.20, 95% CI 5 1.15-1.25). Compared with the HCC group, the non-HCC group had lower post-LT mortality [relative risk (RR) 5 0.85, log-rank P < 0.01] but higher ITT mortality (RR 5 1.25, log-rank P < 0.01) because of a 33 percentage point lower probability of undergoing LT. In conclusion, a longer waiting time before LT for HCC predicted longer post-LT survival in a national transplant registry. Delaying LT for HCC may reduce disparities in ITT survival and access to LT among different indications and thereby improve system utility and organ allocation equity for the overall pool of LT candidates.

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“…Furthermore, HCV eradication in the pre-LT setting prevents recurrence of liver infection (45) and has been associated with higher survival in patients transplanted for HCC. (46) Additionally, Martini et al recently showed that reaching HCV RNA undetectability in the pre-or peri-LT setting could lower the risk of early allograft dysfunction in HCV-positive recipients. (47) This finding, together with our results, should further encourage clinicians to treat HCV patients as early as possible, especially in HCC patients awaiting LT who may be more likely to receive grafts from marginal donors with the consequent higher risk of post-LT complications.…”

Section: Included 1 Cohort Of Hcc Lt Recipients Subsequently Treated mentioning

confidence: 99%

Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus–infected patients treated with direct‐acting antivirals

Zanetto¹,

Shalaby²,

Vitale³

et al. 2017

Liver Transpl

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Concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following direct-acting antiviral (DAA) therapy in patients with cirrhosis with a prior complete oncological response have been raised. Data regarding the impact of HCV treatment with DAAs on wait-list dropout rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Center were considered eligible for the study. After enrollment, patients were divided into 2 groups, depending on whether they underwent DAA treatment while awaiting LT or not. For each patient clinical, serological, and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence rates were calculated. A total of 23 patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) dropout events due to HCC progression were registered (P = 0.90). No significant differences in terms of radiological progression were highlighted (P = 0.16). A total of 9 out of 23 (39%) patients and 14 out of 23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation, or microvascular invasion. During post-LT FU, 1/8 (12.5%) DAA-treated patient and 1/12 (8.3%) control patient experienced HCC recurrence (P = 0.60). In conclusion, viral eradication does not seem to be associated with an increased risk of dropout due to neoplastic progression in HCV-HCC patients awaiting LT. Liver Transplantation 23 1103-1112 2017 AASLD.

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Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20‐year experience

Abstract: HCV patients had lower survival post-LT. HCC alone had no impact on survival. Patient survival decreased in the HCC+/HCV+ group and this appears to be as a consequence of HCV recurrence.

Cited by 17 publications

References 37 publications

Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data

Improved survival outcomes in patients with non‐alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002–2012 United Network for Organ Sharing data

Waiting time predicts survival after liver transplantation for hepatocellular carcinoma: A cohort study using the United Network for Organ Sharing registry

Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus–infected patients treated with direct‐acting antivirals

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