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A healthy lifestyle could prevent most liver cancer and liver-related deaths

Liz Highleyman
17 December 2019
Tracey Simon of Massachusetts General Hospital. Photo by Liz HIghleyman.

A healthy lifestyle, including smoking cessation, moderate drinking, a balanced diet, exercise and weight loss could dramatically reduce the growing burden of liver cancer and deaths due to liver disease, according to a study presented last month at the AASLD Liver Meeting.

Over years or decades, chronic hepatitis B or C infection, heavy alcohol consumption, fatty liver disease and other causes can lead to liver cirrhosis, hepatocellular carcinoma (HCC, the most common type of primary liver cancer) and the need for a liver transplant. HCC is among the fastest-rising causes of cancer-related death worldwide.

"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," Dr Tracey Simon of Massachusetts General Hospital in Boston said in an AASLD press release. "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."

Along with hepatitis B vaccination and hepatitis C treatment, individual lifestyle changes have been shown to reduce the risk of liver cancer and its complications. Dr Tracey Simon and colleagues conducted a study to determine the overall impact of lifestyle on HCC incidence and liver-related mortality.

The study looked at data from two prospective cohorts of US adults. The Nurses’ Health Study (NHS) enrolled more than 121,000 women in 1976. The Health Professionals Follow-up Study (HPFS) enrolled over 51,000 men in 1986. Members of both cohorts provided detailed clinical, lifestyle and dietary information every two to four years.

This analysis included 76,713 women in the NHS and 48,748 men in the HPFS who had complete lifestyle data available in 1986; they were followed through 2012. People who already had viral hepatitis, cirrhosis or liver cancer at study entry were excluded.

The researchers looked at five healthy lifestyle factors:

  • Body mass index: normal weight, or a BMI of 24.9 or lower
  • Physical activity: at least 150 minutes of moderate to vigorous exercise each week
  • Smoking: current non-smoker, including both never-smokers and those who had quit
  • Diet: a score in the upper 40% on the Alternate Healthy Eating Index 2010, which assesses diet quality.
  • Alcohol: one or fewer drinks per day for women or two or fewer drinks for men.

The researchers calculated population-attributable risk, or the proportion of liver cancer cases and liver-related deaths that could have been prevented if all participants adhered to a healthy lifestyle.

To assess whether their findings were generalisable to the population as a whole – which may not be as healthy – they then did a similar analysis based on a nationally representative sample of adults from the 2009-2010 National Health and Nutrition Examination Survey (NHANES).

In the pooled NHS and HPFS group, about two thirds were women, more than 90% were white and the average age was approximately 52 years. As expected, people with more healthy lifestyle factors were less likely to have diabetes, high blood pressure or abnormal blood lipid levels.

Considered individually, each lifestyle factor independently predicted a higher risk of developing liver cancer. Smoking 15 or more cigarettes a day – less than a pack – was associated with a rise in HCC risk. For alcohol use, risk rose even among those who consumed just 5-15 grams per day (14 grams is generally considered a standard drink, for example a bottle of beer, glass of wine or shot of distilled spirits). Liver cancer cases decreased steadily as diet quality and amount of exercise increased.

Not smoking was associated with a 27% reduction in HCC incidence, a healthy diet reduced the risk by 17%, light or no drinking reduced incidence by 21%, a healthy weight lowered the risk by 36% and a healthy level of exercise reduced incidence by 35%. Looking at population-attributable risk, these factors could have prevented 8%, 10%, 14%, 25% and 22% of liver cancer cases, respectively.

Turning to liver-related mortality, meeting the healthy definition for each of the five lifestyle factors reduced liver-related mortality by 31%, 19%, 37%, 48% and 54%, respectively. These factors could have prevented 16%, 8%, 20%, 37% and 35% of deaths, the researchers calculated.

For both liver cancer and liver-related death, body mass index and exercise were the two most important factors. Maintaining a healthy weight or exercising regularly could have prevented 22 to 25% of new liver cancer cases and 35 to 37% of liver-related deaths.

Compared with individuals with no healthy lifestyle factors, HCC risk decreased by 27% among those with one factor, by 58% among those with two factors, by 81% among those with three factors and by 92% among those with four or more factors.

The findings were similar for liver-related death. Compared with those with no healthy lifestyle factors, mortality decreased by 33% among those with one factor, by 66% among those with two factors, by 74% among those with three factors and by 97% among those with four or more factors.

For both HCC cases and liver-related deaths, these patterns remained similar after adjusting for cases of viral hepatitis or cirrhosis that arose during follow-up, Simon reported.

An exploratory analysis of 1401 people who already had cirrhosis at baseline showed that they, too, could still benefit. Those with one healthy lifestyle factor had a 17% lower risk of liver-related death, those with two factors had a 33% lower risk and those with three or more factors had a 47% reduction in relative risk.

Considering the lifestyle factors in combination, having four or more healthy factors predicted an 88% lower risk of developing liver cancer and a 91% reduction in liver-related death. This combination could have prevented 82% of HCC cases and 90% of deaths, the researchers calculated.

Having three healthy factors was associated with a 46% lower risk of HCC and a 63% lower risk of liver-related death. In other words, the triple combination could have prevented 74% of HCC cases and 80% of deaths. Even having just two healthy factors lowered the risk of HCC by 30% and mortality by 40%, preventing 45% of liver cancer cases and 58% of liver-related deaths.

Looking at the NHANES cohort, the researchers found that lifestyle had an even larger impact. In this general population cohort, having four or more healthy lifestyle factors could have prevented 89% of liver cancer cases and 94% of liver-related deaths.

"These findings underscore the enormous potential of primary prevention to reduce the growing burden of HCC and liver-related mortality," the study authors concluded.


Simon TG et al. The impact of healthy lifestyle on the incidence of hepatocellular carcinoma and cirrhosis-related mortality among U.S. adults. AASLD Liver Meeting, Boston, abstract 16, 2019. Hepatology 70:11A, 2019.