Fatty Liver and Diabetes Increase Liver Fibrosis Risk

Tara Haelle

August 25, 2015

The combination of diabetes and nonalcoholic fatty liver disease increase the risk for liver fibrosis more than fivefold, according to a large prospective cohort study published online July 14 in Hepatology.

"These findings underline the significant role of these — potentially modifiable — risk factors in liver fibrosis and stress the importance of early targeting insulin resistance and/or [diabetes mellitus]," write Edith M. Koehler, MD, from the Erasmus MC University Hospital Department of Gastroenterology and Hepatology in Rotterdam, the Netherlands, and associates. "[They also] suggest that [nonalcoholic fatty liver disease] may be an important determinant of clinically relevant fibrosis in a population that has a very low prevalence of viral hepatitis."

The researchers performed abdominal ultrasounds on 3041 Dutch adults aged 45 years and older, with a mean age of 66 years, and used transient elastography to scan their livers between January 2011 and September 2013 in Rotterdam. The researchers also collected blood samples, anthropometric measurements, and data on demographics, medical history, comorbid conditions, smoking history, drug use, and alcohol consumption.

Slightly more than a third (35.5%) of the participants had presence of steatosis on abdominal ultrasound. A liver stiffness measurement of at least 8 kPa denoted clinically relevant fibrosis, and was found in 5.6% of participants.

The odds of fibrosis doubled with each decade of age, going from an incidence of 1.4% in those aged 50 to 60 years, to 3.4% among those aged 60 to 70 years, to 5.5% among those aged 70 to 80 years, to 9.9% in those older than 80 years (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.72 - 3.36; P < .001). In addition, 0.6% had a liver stiffness measurement greater than 13.0 kPa, indicating likely advanced fibrosis or cirrhosis.

The two largest risk factors for fibrosis were presence of hepatitis B or hepatitis C and combined presence of diabetes mellitus and steatosis. Odds for liver stiffness at least 8 kPa or higher were more than five times greater with hepatitis B surface antigen or anti–hepatitis C positivity (OR, 5.38; 95% CI, 1.60 - 18.0; P = .006) and for combined diabetes and nonalcoholic fatty liver disease (OR, 5.20; 95% CI, 3.01 - 8.98; P < .001 for combined presence).

Smoking conferred 77% greater odds of fibrosis (OR, 1.77; 95% CI, 1.16 - 2.70; P = .008), and abnormally high levels of alanine aminotransferase, defined as higher than 40 U/L for men and 30 U/L for women, carried 24% greater odds (OR, 1.24; 95% CI, 1.12 - 1.38; P < .001). An enlarged spleen, defined as greater than 12 cm, increased the odds of fibrosis by 23% (OR, 1.23; 95% CI, 1.09 - 1.40, P = 0.001).

"To date, limited studies have been performed focusing on the prevalence of, and risk factors for liver fibrosis in the general population, as data are mainly derived from autopsy studies or biopsy studies in selected populations," the authors write. Biopsies are invasive, however, and healthy volunteers for the procedure would not likely be representative of the general population, Dr Koehler's team notes, which led the researchers to rely on transient elastography.

"Transient elastography is a very good non-invasive way to measure how much swelling is in the liver, the degree of fibrosis," said David Bernstein, MD, chief of the Division of Hepatology at North Shore University Hospital in Manhasset, New York. The modality was only approved by the US Food and Drug Administration in April 2013, however, and it is not yet widely available, Dr Bernstein added. Therefore, a data set like that in this study would be unusual in the United States.

"I really think that this study probably underestimates the problem that we have in the US because the Dutch are a thinner, healthier population than Americans," he added.

"We have a much higher prevalence of diabetes and obesity, and both are linked to nonalcoholic fatty liver disease" he explained. He noted that approximately 90% of type 2 diabetics have fatty liver disease, and that the US population has a higher proportion of type 2 diabetics than the Dutch population has.

Current estimates suggest that at least 60 million people in the United States have nonalcoholic fatty liver disease, Dr Bernstein said. "You're talking about a tremendous number, and it's only growing because, for the first time in our history, we have a really overweight and obese population of young people who are likely to develop diabetes. This is a problem we're going to have for a long time."

"Most doctors think that fatty liver is benign," he said. "We know now that fatty liver is not benign. The vast majority of people with fatty liver will have no problem, but 2% to 4% will develop cirrhosis, and people with fatty liver are at greater risk of developing cancer."

It is estimated that fatty liver disease will soon overtake hepatitis C as the leading indication for liver transplantation in the United States, said Dr Bernstein.

The research was funded by Erasmus MC University Medical Center, Erasmus University Rotterdam, Netherlands Organization for Scientific Research, Netherlands Organization for Health Research and Development, Research Institute for Diseases in the Elderly, Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, the Municipality of Rotterdam, and the Foundation for Liver Research.

Hepatology. Published online July 14, 2015. Abstract

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