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Comparative Study
. 2018 Apr 7;24(13):1440-1450.
doi: 10.3748/wjg.v24.i13.1440.

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

Takefumi Kimura  1 , Naoki Tanaka  2 , Naoyuki Fujimori  1 , Ayumi Sugiura  1 , Tomoo Yamazaki  1 , Satoru Joshita  1 , Michiharu Komatsu  1 , Takeji Umemura  1 , Akihiro Matsumoto  1 , Eiji Tanaka  1
Affiliations
Comparative Study

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

Takefumi Kimura et al. World J Gastroenterol. .

Abstract

Aim: The 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.

Methods: A 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.

Results: We 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.

Conclusion: A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.

Keywords: Ethanol; Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Risk factor.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that no conflict of interest exists.

Figures

Figure 1
Figure 1
Cumulative incidence rate of hepatocellular carcinoma by Kaplan Meier analysis. The horizontal and vertical axes show days from liver biopsy and cumulative incidence rate of hepatocellular carcinoma, respectively.
Figure 2
Figure 2
Comparison of incidence rates of hepatocellular carcinoma between mild drinking and non-drinking groups. The vertical axis shows incidence rate (percentage) of hepatocellular carcinoma during follow-up time.
Figure 3
Figure 3
Cumulative incidence rate of hepatocellular carcinoma based on data at the time of liver biopsy. A: Age; B: Drinking habit; C: Diabetes mellitus; D: Hypertension; E: Albumin; F: Cholinesterase; G: HbA1c, H: Total cholesterol; I: Triglyceride; J: Platelet; K: Type IV collagen 7S; L: Alpha-fetoprotein; M: Steatosis; N: Fibrosis. The horizontal and vertical axes show days from liver biopsy and cumulative incidence rate of hepatocellular carcinoma, respectively. DM: Diabetes mellitus; HT: Hypertension; Alb: Albumin; CHE: Cholinesterase; TC: Total cholesterol; TG: Triglyceride; Plt: Platelet; T4C7S: Type IV collagen 7S; AFP: Alpha-fetoprotein; F: Fibrosis.
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