Hepatology : official journal of the American Association for the Study of Liver Diseases
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N-terminal propeptide of type 3 procollagen (PRO-C3) is a biomarker of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). This study examines the association between PRO-C3 concentration and liver fibrosis assessed by magnetic resonance elastography (MRE)-measured stiffness (MRE-stiffness) and the heritability of PRO-C3 concentration in a cohort of twins and families with and without NAFLD. We performed a cross-sectional analysis of a well-characterized prospective cohort of 306 participants, including 44 probands with NAFLD-cirrhosis and their 72 first-degree relatives, 24 probands with NAFLD without advanced fibrosis and their 24 first-degree relatives, and 72 controls without NAFLD and their 72 first-degree relatives. ⋯ PRO-C3 concentrations were higher in carriers of the TM6SF2 rs58542926-T allele compared with noncarriers: 15.7 (± 10.5) versus 10.8 (± 5.7) ng/L (P = 0.047). Conclusion: Serum PRO-C3 correlates with MRE-assessed fibrosis, is heritable, shares genetic correlation with liver steatosis and shares environmental correlation with liver fibrosis. PRO-C3 concentration appears to be linked to both fibrosis and steatosis and increased in carriers of the TM6SF2 rs58542926 risk allele.
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Patients listed for liver transplantation (LT) as status 1a currently receive the highest priority on the waiting list. The presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF-3) portends low survival without transplantation, which may not be reflected by the Model for End-Stage Liver Disease-Sodium (MELD-Na) score. We compared short-term waitlist mortality for patients listed status 1a and those with ACLF-3 at listing. ⋯ Multivariable modeling with adjustment for MELD-Na category revealed that patients with ACLF-3 had significantly greater mortality (subhazard ratio, 1.45; 95% confidence interval, 1.31-1.61) within 14 days of listing compared to status-1a candidates. Analysis of the interaction between MELD-Na category and ACLF-3 showed that patients with ACLF-3 had greater risk of 14-day mortality than status-1a-listed patients, across all three MELD-Na categories. Conclusion: Patients with ACLF-3 at the time of listing have greater 14-day mortality than those listed as status 1a, independent of MELD-Na score; these findings illustrate the importance of early transplant evaluation and consideration of transplant priority for patients with ACLF-3.
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Approved treatment for hepatitis C virus (HCV) with all-oral direct-acting antivirals (DAA) therapy is now entering into its fourth year; however, little has been reported on the real-world clinical (decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]) and economic outcomes. A retrospective cohort analysis of the Truven Health MarketScan Database (2012-2016) was conducted. In a cohort of 26,105 patients with newly diagnosed HCV, 30% received all-oral DAA therapy (DAA group) and 70% were not treated (untreated group). ⋯ The mean adjusted costs were not statistically different between the two groups among patients without cirrhosis. Conclusion: In the short term, all-oral DAA treatment for HCV infection was associated with a decreased risk of developing HCC and DCC, resulting in decreased health care costs, especially in patients with cirrhosis. A longitudinal study is necessary to confirm our findings.