Because only the alcoholics with chronic liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers.

Introduction: The burden of hepatocellular carcinoma (HCC) occurring in patients with alcoholic liver disease (ALD) is increasing at an alarming rate. The aims of this study were to compare the patient and tumor characteristics of HCC occurring in ALD-alone relative to and in addition to other chronic liver diseases. Methods: Patients diagnosed with HCC between 2000 and 2014 were identified at 5 US clinical centers. The patients were categorized as ALD-alone, ALD plus viral hepatitis, or a non-ALD etiology. Clinical and tumor characteristics among the 3 groups were compared, and survival probability was estimated by the Kaplan-Meier method. The frequency of noncirrhotic HCC was compared across the 3 groups. Results: A total of 5,327 patients with HCC were analyzed. Six hundred seventy (12.6%) developed HCC due to underlying ALD. Ninety-one percent of ALD-related HCC arose in men, in contrast to non-ALD etiologies where men accounted for 70% of HCCs cases (P < 0.001). Patients with ALD-alone-related HCC were older at diagnosis and had tumors less likely to be detected as part of routine surveillance. The ALD-alone cohort was least likely to be within the Milan criteria and to undergo liver transplantation. Overall survival in the ALD-alone HCC cohort was lower than the other 2 groups (1.07 vs 1.31 vs 1.41 years, P < 0.001). HCC in the noncirrhotic ALD cohorts occurred in only 3.5% of the patients compared with 15.7% in patients with non-ALD etiologies (P < 0.001). DISCUSSION: HCC occurring in patients with ALD occurred mostly in older men and almost exclusively in a cirrhotic background. They present with advanced tumors, and their survival is lower than HCCs occurring in non-ALD.

INTRODUCTION: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. METHODS: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. RESULTS: In the DAA era (2014–2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88–0.99, P = 0.019), without change in trends of other liver diseases–related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03–1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81–0.97, P = 0.009) along with similar trends for HCV-HCC—increase in noncirrhotic cases (OR 1.35, 95% CI 1.08–1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86–0.98, P = 0.012)—were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. DISCUSSION: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.

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