Radiologic characteristics and prognostic outcomes in non-alcoholic fatty liver disease-related versus alcohol-related hepatocellular carcinoma: a comparative cohort study

Kuldeep Singh; Supriya Sundar Mishra; Anamika Shahi

doi:10.18203/2349-3259.ijct20260361

Authors

Kuldeep Singh Department of Gastroenterology, Apex Hospital, Jaipur, Rajasthan, India
Supriya Sundar Mishra Department of Radiology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India
Anamika Shahi Department of Radiology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India

DOI:

https://doi.org/10.18203/2349-3259.ijct20260361

Keywords:

NAFLD, Hepatocellular Carcinoma, Magnetic resonance imaging, Computed tomography, Treatment

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the fastest-growing etiologies of hepatocellular carcinoma (HCC), while alcohol remains a dominant cause of cirrhosis and HCC in India. Differences in tumor morphology, biological behavior, and outcomes between these two etiologies remain inadequately defined in the Indian population. This study aims to compare radiologic features and prognostic outcomes in NAFLD-related and alcohol-related HCC patients.

Methods: This retrospective cohort study conducted at Apex Hospital included 50 consecutive HCC patients evaluated between September 2014 and October 2015. Etiology was classified as NAFLD (n=25) or alcohol-related liver disease (ALD) (n=25). All patients underwent contrast-enhanced computed tomography (CT) or MRI at presentation. Tumor morphology, liver imaging reporting and data system (LI-RADS) imaging features, vascular invasion, extrahepatic disease, and portal hypertension indicators were analyzed. Clinical parameters including serum alpha-fetoprotein (AFP), Child-Pugh and model for end-stage liver disease (MELD) scores, metabolic comorbidities, and treatment modalities were compared. Survival was assessed at 1 and 3 years.

Results: NAFLD-HCC patients were older (mean 62 vs 54 years), had higher rates of diabetes (68% vs 24%), and more often presented with solitary large lesions (mean size 6.1 cm vs 4.2 cm). Alcohol-HCC patients showed significantly higher rates of multifocal disease (56% vs 28%) and portal hypertension markers. Portal vein thrombosis was more common in alcohol-HCC (36% vs 16%). One-year survival was higher in the NAFLD group (68% vs 40%; p<0.05). Three-year survival remained better in NAFLD-HCC (24% vs 8%).

Conclusions: NAFLD-and alcohol-related HCC represent distinct phenotypic and prognostic subtypes. NAFLD-HCC is characterized by large solitary tumors but better liver function and improved short-term survival, while alcohol-HCC exhibits more advanced cirrhosis, multifocal disease, and worse outcomes. Etiology-specific surveillance strategies are warranted.

References

Estes C, Anstee QM, Arias-Loste MT, Heike B, Stefano B, Joan C, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67(1):123-33.

Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: new trends. Hepatology. 2020;72(1):175-89.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.

Anstee QM, Reeves HL, Kotsiliti E, Govaere O, Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol. 2019;16(7):411-28.

Kalra S, Unnikrishnan AG, Baruah MP. Metabolic disease trends in India: a looming public health challenge. J Assoc Physicians India. 2019;67(4):83-7.

Das K, Chowdhury A. Epidemiology of nonalcoholic fatty liver disease in India. J Clin Exp Hepatol. 2020;10(3):245-54.

Reddy PK, Patel V, Jha P. Patterns of alcohol use and related harm in India. Indian J Psychol Med. 2019;41(2):135-42.

World Health Organization. Global status report on alcohol and health 2018. Geneva: World Health Organization; 2018. Available at: https://www.who.int/publications/i/item/9789241565639. Accessed on 3 July 2025.

Lackner C, Tiniakos D. Fibrosis and alcohol-related liver disease. J Hepatol. 2019;70(2):294-304.

Mittal S, Sada YH, El-Serag HB, Fasiha K, Zhigang D, Sarah T, et al. Hepatocellular carcinoma in the absence of cirrhosis in patients with nonalcoholic fatty liver disease. Hepatology. 2016;63(3):827-38.

Dyson J, Jaques B, Chattopadyhay D, Rajiv L, Janine G, Debasish D, et al. Hepatocellular carcinoma: the impact of obesity, type 2 diabetes and a multidisciplinary team. Hepatology. 2014;60(6):1957-68.

Kanwal F, Singal AG. Surveillance for hepatocellular carcinoma: current best practice and future direction. Gastroenterology. 2021;160(6):2065-77.

Stickel F, Hampe J. Genetic risk factors in alcoholic liver disease. J Hepatol. 2020;72(2):335-51.

European Association for the Study of the Liver. EASL clinical practice guidelines: management of alcohol-related liver disease. J Hepatol. 2018;69(1):182-236.

Marrero JA, Kulik LM, Sirlin CB, Andrew XZ, Richard SF, Michael MA, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the AASLD. Hepatology. 2018;67(1):358-80.

American College of Radiology. LI-RADS® v2018 Manual. Reston (VA): American College of Radiology; 2018.

Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020-2.

Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol. 2018;69(3):526-49.

Wong CR, Nguyen MH, Lim JK. Hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. J Clin Oncol. 2016;34(27):3439-47.

Heimbach JK, Kulik LM, Finn RS, Claude BS, Michael MA, Lewis RR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358-80.

Sharma M, Rameshbabu CS. Collateral pathways in portal hypertension. Indian J Radiol Imaging. 2018;28(1):52-61.

Chalasani N, Younossi Z, Lavine JE, Michael C, Kenneth C, Mary R, et al. The diagnosis and management of NAFLD: practice guidance. Hepatology. 2018;67(1):328-57.

Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. Hepatology. 2012;56(6):2362-71.

Ascha MS, Hanouneh IA, Lopez R, Tarek Abu-Rajab T, Ariel FF, Nizar NZ. The incidence and risk factors of hepatocellular carcinoma in patients with alcoholic cirrhosis. Hepatology. 2010;52(1):79-85.

Hoshida Y, Fuchs BC, Bardeesy N, Baumert TF, Chung RT. Pathogenesis and prevention of hepatitis C virus-associated hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2014;11(2):101-13.

Dhir M, Lyden ER, Smith LM, Are C. Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta‐analysis. HPB (Oxford). 2012;14(9):635‐45.

Yilmaz Y. NAFLD-associated hepatocellular carcinoma: epidemiology, clinical features and prevention. Hepatology. 2012;56(6):2407-8.

Singal AG, Rich NE, Mehta N, Andrea B, Anjana P, Maarouf H, et al. Direct-acting antiviral therapy not associated with recurrence of hepatocellular carcinoma in a multicenter North American cohort study. Clin Gastroenterology. 2019;156(6):1683-92.

Terrault NA, Lok ASF, McMahon BJ, Kyong-Mi C, Jessica PH, Maureen MJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-99.