A Healthy Lifestyle May Help Prevent Liver-Related Deaths

BOSTON – Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that a substantial burden of hepatocellular carcinoma (HCC) and cirrhosis-related deaths may be prevented by lifestyle modifications to diet, alcohol use and exercise. 

HCC and cirrhosis incidence are on the rise in the U.S., and deaths related to these illnesses are also accelerating at an alarming pace, prompting researchers from Massachusetts General Hospital and Harvard Medical School to analyze whether adopting a healthier lifestyle might reduce HCC incidence and deaths from cirrhosis. 

“We wanted to conduct this study because there is growing evidence that both HCC- and cirrhosis-related mortality are largely preventable. Several prior studies have found that individual lifestyle factors, which include body weight, exercise, alcohol use, smoking and diet, contribute to the risk for developing HCC. However, no prior study had quantified the overall contribution of multiple lifestyle factors on the risk for HCC and liver-related mortality,” says Tracey G. Simon, MD, instructor of medicine at Harvard Medical School and Massachusetts General Hospital, and the study’s lead author. “We wanted to estimate how many cases of HCC and deaths from cirrhosis could have been prevented, in our study population, if everyone had adhered to a healthy lifestyle.” 

The study was driven by the rising epidemic of nonalcoholic fatty liver disease (NAFLD) worldwide, and the need to develop treatment approaches that are both feasible and effective at the population level, says Dr. Simon. 

“Right now, there are not yet any effective medications to reverse liver fibrosis or prevent HCC. It is essential that we focus on controlling risk factors through primary prevention. Lifestyle modification represents a primary prevention effort that is likely to be a more effective and feasible way to prevent HCC and liver-related mortality, at the population level, explains Dr. Simon of the focus.”

This nationwide, prospective cohort study included data on adult men and women with no known liver disease at the beginning of the study. Study participants provided detailed clinical, lifestyle and dietary data every other year from 1986 through 2012. All new HCC cases and deaths were confirmed. A low-risk lifestyle group met all of the following criteria: never smoked or prior smoking less than five pack-years, no or moderate alcohol use, a body-mass index between 18.5 and 24.9, weekly physical activity and a healthy diet ranking in the upper 40 percent of the Alternative Healthy Eating Index (which measures diet quality). All other study subjects were placed in a high-risk group. 

The researchers used Cox proportional hazard regression modeling to estimate multivariate-adjusted hazard ratios (HRs) and 95 percent confidence intervals (CIs) for incident HCC and cirrhosis-related mortality. They calculated the population-attributable risk (PAR) of nonadherence to a low-risk lifestyle by comparing relative risks and incidence rates between the two groups, and then assessed the PARs for each modifiable lifestyle risk factor to estimate the percentage of cases that could be prevented by modifying those factors in isolation.

Among 121,893 adults followed for 2,388,811 person-years, the researchers confirmed 121 new HCC cases and 350 cirrhosis-related deaths. Multivariate-adjusted HRs for five versus zero modifiable risk factors were 3.59 (95 percent CI 1.50-7.42) for incident HCC and 4.27 (95 percent CI 56-98) for cirrhosis-related mortality. The PAR for a high-risk versus low-risk lifestyle was 90 percent (95 percent CI 2.06-11.69) for incident HCC and 89 percent (95 percent CI 43-98) for liver-related mortality. Women and men had similar associations. Overall, overweight/obesity was the most significant modifiable risk factor, with a PAR of 36 for HCC incidence and 42 for cirrhosis-related mortality.

“Our findings strongly support continued efforts to develop public health policies for lifestyle modification, to prevent HCC and liver-related mortality. Our data suggested that adherence to a healthy overall lifestyle could potentially prevent more than 30,000 liver-related deaths in the United States each year,” says Dr. Simon. “We are working to validate these findings in additional population-based cohorts, and look forward to planning large-scale studies of multi-dimensional diet and lifestyle interventions for patients with established liver disease.”

Dr. Simon will the study entitled “The Impact of Healthy Lifestyle on the Incidence of Hepatocellular Carcinoma and Cirrhosis-Related Mortality Among U.S. Adults” on Monday, Nov. 11 at 8 AM in the Auditorium of the Hynes Convention Center. The corresponding abstract (number 0016) can be found in the journal, HEPATOLOGY.

About the AASLD 

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Abstract 0016: THE IMPACT OF HEALTHY LIFESTYLE ON THE INCIDENCE OF HEPATOCELLULAR CARCINOMA AND CIRRHOSIS-RELATED MORTALITY AMONG U.S. ADULTS

Authors: Dr. Tracey G Simon, Massachusetts General Hospital, Dr. Mi Na Kim, Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Dr. Dawn Chong, Harvard Medical School, Dr. Charles Fuchs, Cancer Center, Yale University, Dr. Jeffrey Meyerhardt, Dana Farber Cancer Center, Harvard University, Dr. Edward Giovannucci, Harvard T. H. Chan School of Public Health, Dr. Meir Stampfer, Epidemiology, Harvard University School of Public Health, Dr. Xuehong Zhang, Channing Department of Network Medicine, Brigham and Women’s Hospital and Dr. Andrew Chan, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School

Abstract Text

Background:

In the U.S., the incidence of and mortality from cirrhosis and hepatocellular carcinoma (HCC) are accelerating at an alarming pace. While individual modifiable lifestyle factors have been associated with elevated risk of incident HCC and cirrhosis-related death, little is known about the shared impact of lifestyle on major hepatic outcomes. Specifically, the proportion of incident HCC cases and cirrhosis-related deaths that might be prevented by adopting a healthy lifestyle are unknown.

Methods:

We conducted a nationwide, prospective cohort study of adult men and women without known liver disease at baseline. All subjects provided detailed clinical, lifestyle and dietary data biennially from 1986-2012. All incident HCC cases and deaths were confirmed. The low-risk lifestyle group met all 5 of the following criteria: (1) never/prior smoking (pack-years<5), (2) no/moderate alcohol use (<1 drink/day [women], <2 drinks/day [men]), (3) BMI 18.5-24.9kg/m 2, (4) weekly physical activity >=6 metabolic equivalent task (MET)- hours, and (5) healthy diet (upper 40% of the Alternative Healthy Eating Index). All others comprised the high-risk group. Using Cox proportional hazard regression modeling, we estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HCC and cirrhosis-related mortality. We calculated the population-attributable risk (PAR) of nonadherence to a low- risk lifestyle, by comparing the relative risks and incidence rates between groups. We further assessed the partial PARs for each modifiable risk factor, to estimate the percentage of cases that could be prevented by modifying individual risk factors, in isolation.

Results:

Among 121,893 adults, followed for 2,388,811 person-years, we confirmed 121 incident HCC cases and 350 cirrhosis-related deaths. The multivariable-adjusted HRs for 5 vs. 0 modifiable risk factors were 3.59 (95% CI 1.50-7.42) for incident HCC, and 4.27 (95% CI 2.06-11.69) for cirrhosis-related mortality. The PAR for high- vs. low-risk lifestyle was 90% (95% CI 56-98) for incident HCC, and 89% (95% CI 43-98) for liver-related mortality (Table 1). Similar associations were observed among women and men, and after further adjusting for the development of incident viral hepatitis or cirrhosis over follow-up. Overall, the single modifiable risk factor with the largest PAR% was overweight/obesity (BMI>=25kg/m 2; PAR% 36 [95% CI 22-50] for HCC, and 42 [95% CI 19-54] for cirrhosis- related mortality, respectively).

Conclusion:

A substantial burden of HCC and cirrhosis-related mortality may be prevented by lifestyle modification. Developing effective strategies

to prevent incident HCC and cirrhosis-related mortality should remain a high priority.

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