NASH rapidly overtaking hepatitis C as cause of liver cancer
YOUR DOSE OF MEDICINE - Charles C. Chante MD (The Philippine Star) - June 16, 2019 - 12:00am

Nonalcoholic steatohepatitis (NASH) is rapidly eclipsing hepatitis C virus (HCV) infection as the leading contributor to liver cancer in the United States.

Researchers reported on their analysis of past prevalence of HCV, NASH, and alcoholic cirrhosis and prediction of future trends and their effect on hepatocellular carcinoma.

The analysis, based on data shows that the prevalence of HCV has been in steady decline since 2005 and that decline is forecast to continue. From a prevalence of 3.22 million cases in 2005, researchers have forecast a decline to 1.06 million cases by 2025.

At the same time, even a conservative linear model for the changing prevalence of NASH forecast a rapid increase from 1.37 million cases in 2005 to 17.95 million in 2025. The exponential model suggested an increase from 2.41 million in 2005 to 42.34 million in 2025.

In terms of effect on the prevalence of hepatocellular carcinoma (HCC), the modeling suggested cases of HCV-related liver cancer were predicted to peak at around 29,000 cases in 2025. In contrast, the prevalence of HCC from NASH is forecast to increase from between 5,000 and 6,000 cases in 2005 to 45,000 in 2025 by the conservative linear model or even as high as 106,000 cases according to the exponential model. It overtook HCV infection as a cause of liver cancer by around 2015.

Despite the lack of existing data on which to work, the general trends of our prediction models are consistent with the documented trends of liver transplant etiology, as well as 2010 insurance data indicating nonalcoholic fatty liver disease/NASH as the leading etiology associated with HCC.

The study used liver transplant data as a proxy for the prevalence of hepatocellular carcinoma and also took into account the natural history of the disease. Between 5 percent and 20 percent of untreated HCV infections will go on to develop into cirrhosis, and of patients with HCV-related cirrhosis, around 15 percent will develop HCC within 10 years.

In the case of NASH, the authors cited research suggesting that around 35 percent of patients go on to develop progressive fibrosis, that progression to cirrhosis takes around 29 years, and that the risk of progression to HC ranged from 2.4 percent over 7 years to 12.8 percent over 3 years.

A higher proportion of patients with NASH develop cirrhosis, but of those who develop cirrhosis, the probability of developing HCC is higher in patients with HCV. In contrast, HCV progression to HCC rarely occurs in noncirrhotic patients.”

It was important to explore projected trends in etiology of hepatocellular carcinoma to inform the development of screening, diagnostic, and treatment approaches, particularly given potential differences in the pathology, natural history, and treatment options for NASH-related and HCV-related liver cancer.

Histologically, NASH shares characteristics with alcoholic liver disease, primarily proinflammatory fat accumulation in parenchymal cells, (and) key players in NASH progression to HCC are suggested to include genetic modifications, proinflammatory high-fat and/or high-fructose diets, and oxidative and endoplasmic cellular stresses. In HCV progression to HCC, the presence of the HCV core protein may induce HCC without the prerequisite load of genetic errors normally required for cancer development, skipping or accelerating some of the classic steps of cancer induction.

The authors did note that their model represented a base scenario that assumed the environmental and genetic factors driving NASH would continue along the path of current trends.

Therefore, the possibility exists that our models underestimate the response of the medical community in addressing the rising nonalcoholic fatty liver disease/NASH epidemic.”

HEPATITIS C NONALCOHOLIC STEATOHEPATITIS
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