Nonalcoholic fatty liver disease and hepatocellular carcinoma: A weighty connection

By Brad Q. Starley, Christopher J. Calcagno, S. Harrison. Hepatology, 2010

1,379 citations recorded by the source corpus.

Hepatocellular carcinoma (HCC) is a common and deadly malignancy that is increasing in incidence in developed countries. The emergence of hepatitis C virus (HCV) accounts for about half of this increase in HCC, although the etiology of HCC in 15%‐50% of new HCC cases remains unclear. The most common form of chronic liver disease in developed countries is nonalcoholic fatty liver disease (NAFLD), which encompasses a broad spectrum of histopathology. The prevalence of NAFLD, including the more aggressive nonalcoholic steatohepatitis (NASH), is increasing with the growing epidemics of diabetes and obesity. NASH can progress to cirrhosis and its related complications. Growing evidence suggests that NASH accounts for a large proportion of idiopathic or cryptogenic cirrhosis, which is associated with the typical risk factors for NASH. HCC is a rare, although important complication of NAFLD. Diabetes and obesity have been established as independent risk factors for the development of HCC. New evidence also suggests that hepatic iron deposition increases the risk of HCC in NASH‐derived cirrhosis. Multiple case reports and case reviews of HCC in the setting of NASH support the associations of diabetes and obesity with the risk of HCC, as well as suggest age and advanced fibrosis as significant risks. Insulin resistance and its subsequent inflammatory cascade that is associated with the development of NASH appear to play a significant role in the carcinogenesis of HCC. The complications of NASH, including cirrhosis and HCC, are expected to increase with the growing epidemic of diabetes and obesity. (HEPATOLOGY 2010;51:1820–1832)

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/12aabd74a847d6ec37728549e7343272f795e200

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

1. Z. Younossi
2. Christopher D. Byrne
3. G. Targher

In Epidemiology

1. Z. Younossi
2. Christopher D. Byrne
3. G. Targher
4. L. Henry
5. P. Scherer
6. Z. Goodman
7. Haiming Cao
8. Herbert Tilg

In Hepatology

1. Z. Younossi
2. Christopher D. Byrne
3. G. Targher
4. Z. Goodman

Citations in the corpus

• Mechanisms of Hepatic Triglyceride Accumulation in Nonalcoholic Fatty Liver Disease (2013, neutral): “Whereas simple steatosis is characterized by a relatively favorable clinical course, NASH much more frequently progresses to cirrhosis and hepatocellular carcinoma [1, 2].”
• The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe (2016, methodology): “(20,21) Given the limited amount of data available for the age-specific natural history of NAFLD, a base transition matrix without regard to age was built from the published literature (Supporting Table S2)(22-31); where data gaps existed, values were imputed from the primary sources used in a recen”
• Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation (2014, background): “However, consideration should be given to treating those with compensated disease who are awaiting transplant with modified interferon and ribavirin dosing, especially if the genotype is favorable (genotype II, III), the patient has a potential living donor, or MELD exception points for HCC.90 This ”
• NAFLD: a multisystem disease. (2015, background): “Although it is less certain whether simple steatosis increases risk of HCC, it is now becoming clear that NASH is a risk factor for HCC, even in people without cirrhosis [30–32].”
• Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. (2014, background): “lower rate of HCC development among NASH patients has been reported in several additional studies.(10-17) Despite the low incidence of HCC among NASH patients, the overall increasing prevalence of NAFLD will undoubtedly lead to increased prevalence of NASH and a subsequent increased prevalence of NA”
• Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis Through Adipose Tissue Crosstalk (2016, background): “NAFLD and NASH can be associated with insulin resistance, though not in all cases, and a subgroup of individuals among this group has a higher risk of progressing to cirrhosis and, eventually, hepatocellular carcinoma (Cohen et al., 2011; Starley et al., 2010).”
• Pathologic criteria for nonalcoholic steatohepatitis: Interprotocol agreement and ability to predict liver‐related mortality (2011, background): “In summary, our data confirm that patients with NASH are at high risk for LRM.(1-14,21-30) We have also shown that a certain degree of agreement exists between all four sets of pathologic criteria for NASH.”