Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis

Abstract

AIMThe impact of mild drinking habit (less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease (NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD.METHODSA total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with non-alcoholic steatohepatitis, 26% with advanced fibrosis (F3-4)] were divided into the mild drinking group with ethanol consumption of less than 20 g/d (mild drinking group, n = 93) and the non-drinking group (n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma (HCC) occurrence were compared between the groups.RESULTSWe observed significant differences in male prevalence (P = 0.01), platelet count (P = 0.04), and gamma-glutamyl transpeptidase (P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group (6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox’s regression model revealed that hepatic advanced fibrosis (F3-4) (P < 0.01, risk ratio: 11.60), diabetes mellitus (P < 0.01, risk ratio: 89.50), and serum triglyceride (P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal (P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis (F3-4), however, a drinking habit (P = 0.04, risk ratio: 4.83), alpha-fetoprotein (P = 0.01, risk ratio: 1.23), and diabetes mellitus (P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence.CONCLUSIONA mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.

Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies

“…Although both studies evaluated lifetime drinking and made careful efforts to exclude previous drinkers and binge drinkers and adjusted for multiple confounders, the cross‐sectional study by Dunn and colleagues () found protective effects of low alcohol use, whereas the longitudinal study by Ajmera and colleagues () reported harmful effects. Similarly, although low alcohol use has been found protective from steatosis in numerous cross‐sectional Japanese studies, the only longitudinal ones reported increased HCC risk (Kawamura et al, ; Kimura et al, ).…”

“…Vilar‐Gomez and colleagues () found that, in patients with NAFLD cirrhosis, low alcohol use (<30 g/d for men and <20 g/d for women) was associated with an increased risk of death or liver transplantation (hazard ratio 2.3), hepatic decompensation (hazard ratio 1.7), and HCC (hazard ratio 3.2) compared to abstinence, a finding that reinforces the need for absolute alcohol abstinence in patients with cirrhosis. Two additional studies found an increased risk for HCC among NAFLD patients with advanced fibrosis or cirrhosis reporting any alcohol use (Ascha et al, ; Kimura et al, ).…”

Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development

“…HCC is a leading cause of cancer mortality, with poor prognosis and very few effective therapeutic options. Risk factors for HCC include persistent infection with hepatitis B and C viruses, obesity, metabolic syndrome, nonalcoholic steatohepatitis, alcohol consumption, exposure to aflatoxins, and inborn errors of metabolism, such as α‐1 antitrypsin deficiency, tyrosinemia, and citrin deficiency . Recently, gut microbiota and BAs were also shown to be associated with HCC development …”

Miglitol attenuates non‐alcoholic steatohepatitis in diabetic patients

“…Other glucose‐lowering agents had already been administered in three patients. Non‐alcoholic steatohepatitis was suspected based on the criteria of: (i) the presence of hepatorenal contrast and increased hepatic echogenicity on abdominal ultrasonography; (ii) ethanol consumption of <20 g/day; (iii) the absence of other causes of liver dysfunction, such as viral hepatitis, drug‐induced liver injury, autoimmune liver diseases, primary sclerosing cholangitis, Wilson disease, hereditary hemochromatosis, and citrin deficiency; and (iv) histologically confirmed using biopsied specimens. Body weight (BW) and height were measured before liver biopsy in a fasting state.…”

“…The presence of obesity was defined as a body mass index (BMI) >25 kg/m 2 according to criteria released by the Japan Society for the Study of Obesity. Clinical information was also recorded, with the presence of hypertension and hyperlipidemia being evaluated as described previously …”