From the AGA Journals

Hepatitis C drove steep rises in cirrhosis, HCC, and related deaths

Publish date: October 6, 2015
Author(s):
Amy Karon

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Improving treatment not enough to reduce liver disease burden

Despite recent advances in hepatitis C virus treatment, many infected patients have preexisting liver fibrosis that puts them at risk for cirrhosis and hepatocellular carcinoma. Meanwhile, risk factors for nonalcoholic fatty liver disease (NAFLD) are increasingly prevalent. In this study, the investigators sought to understand the contribution of liver disease etiology to trends in adverse liver outcomes (the prevalence, incidence, and mortality of cirrhosis and HCC). They identified all VA health care users from 2001 to 2013 with diagnoses of cirrhosis (n = 129,998) or HCC (n = 21,326) and their liver disease etiology, and compared outcomes by calendar year.

Dr. Barry Schlansky

Over the study period, marked increases in cirrhosis prevalence (59%), cirrhosis mortality (52%), HCC incidence (164%), and HCC mortality (185%) were observed in this national VA cohort. The increasing prevalence of cirrhosis was mainly driven by increasing contributions from HCV or NAFLD liver disease, but rises in mortality from cirrhosis and both incidence and mortality from HCC were almost entirely due to HCV. Based on these trends, the researchers forecasted that the prevalence of cirrhosis will plateau and begin to decline in 2021 (2020 in the HCV subgroup), but rates of HCC will continue to surge.

Although these results differ from two recent analyses of the national cancer surveillance registry (SEER) that found decelerations in HCC incidence and mortality in recent years, the current study included methodologic features (stratification by liver disease etiology and absence of age standardization) that likely facilitated more accurate estimates of HCC incidence and mortality. The generalizability of VA data to the general population is always debated (the former is nearly exclusively men with a higher prevalence of HCV infection and other liver disease risk factors, all of whom have access to medical care), yet the researchers rightly note that the time trends in cirrhosis and HCC outcomes (rather than absolute numbers) are still applicable to the non-VA population, particularly men. This study highlights the dramatic rise in cirrhosis and HCC, and associated deaths from these conditions, over the last decade. In addition to aggressive treatment of the underlying cause of liver disease, meaningful reductions in the burden of advanced liver disease will require a renewed focus on measures to improve adherence with maintenance care for cirrhotic patients, especially liver cancer screening.

Dr. Barry Schlansky is assistant professor, division of gastroenterology and hepatology, department of medicine, Oregon Health and Science University, Portland. He has no conflicts of interest.


 

FROM GASTROENTEROLOGY

References

Cirrhosis nearly doubled among Veterans Affairs patients between 2001 and 2013, while cirrhosis-related mortality rose by about 50% and deaths from hepatocellular carcinoma almost tripled, investigators reported in the November issue of Gastroenterology.

Hepatitis C virus infection was “the overwhelming driver of these trends, with smaller contributions from alcoholic liver disease, nonalcoholic fatty liver disease, and other liver diseases,” said Dr. Lauren Beste of the University of Washington, Seattle, and her associates. Based on their data, the prevalence of cirrhosis in the United States will peak in 2021, they said. “In contrast, the incidence of HCC continues to increase, confirming worrisome predictions of rapid growth put forward by work (Gastroenterology. 2010;138[2]:513-21) conducted” in the early 2000s.

New HCV infections have dropped sharply in the United States since about 1990, but cases of HCV-related cirrhosis and HCC continue to rise as chronically infected patients age and their liver disease progresses. Although the burden of cirrhosis and HCC due to HCV infection is expected to peak in about the year 2020, the population-level effects of nonalcoholic fatty liver disease, alcoholic liver disease, and hepatitis B virus infection remained unclear, the investigators said. Therefore, they retrospectively studied underlying etiologies among a national cohort of almost 130,000 Veterans Affairs patients with cirrhosis and more than 21,000 patients with HCC between 2001 and 2013 (Gastroenterology 2015. doi: 10.1053/j.gastro.2015.07.056).

In 2013, the VA cared for more than 5.7 million patients, including about 1% with cirrhosis and 0.13% with HCC. Between 2001 and 2013, the prevalence of cirrhosis almost doubled, rising from 664 to 1,058 cases for every 100,000 patients. Deaths among cirrhotic patients also increased by about half, rising from 83 to 126 for every 100,000 patient-years. These liver-related deaths were mainly caused by HCC, whose incidence rose about 2.5 times from 17 to 45 per 100,000 patient-years, Dr. Beste and her associates reported.

Notably, deaths due to liver cancer rose threefold – from 13 to 37 per 100,000 patient-years between 2001 and 2013, “driven overwhelmingly by HCV with much smaller contributions from NAFLD and alcoholic liver disease,” said the researchers. By 2013, almost half of cirrhosis cases and related deaths occurred among HCV-infected patients, as did 67% of HCC cases and related deaths, they noted.

About 60% of patients with cirrhosis and HCV infection also had a longstanding history of alcohol use, the researchers noted. Addressing both factors, as well as diabetes, obesity, and other drivers of nonalcoholic fatty liver disease, could help ease the national burden of liver disease and liver-related mortality among U.S. veterans and other groups, they added. “The increasing burden of cirrhosis and HCC highlights the need for greater efforts to address their causes at a population level,” Dr. Beste and her associates wrote. “Health care systems will need to accommodate rising numbers of patients with cirrhosis and HCC.”

The Department of Veterans Affairs and the Veterans Health Administration funded the study. The investigators declared no competing interests.

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