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. 2020 Oct 29;12(11):3182.
doi: 10.3390/cancers12113182.

Non-Alcoholic Steatohepatitis as a Risk Factor for Intrahepatic Cholangiocarcinoma and Its Prognostic Role

Stefania De Lorenzo  1 , Francesco Tovoli  2 , Alessandro Mazzotta  3 , Francesco Vasuri  4 , Julien Edeline  5 , Deborah Malvi  4 , Karim Boudjema  3 , Matteo Renzulli  6 , Heithem Jeddou  3 , Antonietta D'Errico  4 , Bruno Turlin  7 , Matteo Cescon  8 , Thomas Uguen  9 , Alessandro Granito  2 , Astrid Lièvre  10 , Giovanni Brandi  1
Affiliations

Non-Alcoholic Steatohepatitis as a Risk Factor for Intrahepatic Cholangiocarcinoma and Its Prognostic Role

Stefania De Lorenzo et al. Cancers (Basel). .

Abstract

Non-alcoholic fatty liver disease (NAFLD) and its most aggressive form, non-alcoholic steatohepatitis (NASH), are causing a rise in the prevalence of hepatocellular carcinoma. Data about NAFLD/NASH and intrahepatic cholangiocarcinoma (iCCA) are few and contradictory, coming from population registries that do not correctly distinguish between NAFLD and NASH. We evaluated the prevalence of NAFLD and NASH in peritumoral tissue of resected iCCA (n = 180) and in needle biopsies of matched liver donors. Data of iCCA patients were subsequently analysed to compare NASH-related iCCA (Group A), iCCA arisen in a healthy liver (Group B) or in patients with classical iCCA risk factors (Group C). NASH was found in 22.5% of 129 iCCA patients without known risk factors and in 6.2% of matched controls (risk ratio 3.625, 95% confidence interval 1.723-7.626, p < 0.001), while NAFLD was equally represented in both groups. The overall survival of NASH-related iCCA was inferior to that of patients with healthy liver (38.5 vs. 48.1 months, p = 0.003) and similar to that of patients with known risk factors (31.9 months, p = 0.948), regardless of liver fibrosis. The multivariable Cox regression confirmed NASH as a prognostic factor (hazard ratio 1.773, 95% confidence interval 1.156-2.718, p = 0.009). We concluded that NASH (but not NAFLD) is a risk factor for iCCA and might affect its prognosis. Dissecting NASH from NAFLD by histology is necessary to correctly assess the actual role of these conditions. Prevention protocols for NASH patients should also consider the risk for iCCA and not only HCC. Mechanistic studies aimed to find a direct pathogenic link between NASH and iCCA could add further relevant information.

Keywords: intrahepatic cholangiocarcinoma; liver cirrhosis; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; outcome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patients disposition. iCCA, intrahepatic cholangiocarcinoma; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.
Figure 2
Figure 2
Kaplan-Meyer overall survival analysis of NASH patients (n = 29). (A) Patients without any known causes of liver disease (n = 100). (B) Patients with classical risk factors for intrahepatic cholangiocarcinoma (n = 51).
See this image and copyright information in PMC

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