Miriam E. Tucker

April 11, 2014

LONDON, United Kingdom — Nonalcoholic fatty liver disease is an independent predictor of cardiometabolic risk, according to 2 new studies.

Taken together, these findings "contribute to a large body of evidence showing nonalcoholic fatty liver disease may pose a cardiovascular risk above and beyond that conferred by traditional risk factors," said Frank Lammert, MD, PhD, professor of internal medicine at the Saarlande University Medical Center in Homburg, Germany.

"I think the key message for clinical practice is that these diseases are closely correlated, and clinical practitioners should be aware of this," he told Medscape Medical News.

Dr. Lammert, who was not involved in either study, spoke during a press briefing here at European Association for the Study of the Liver International Liver Congress 2014, where results from the 2 studies were presented.

In the Japanese study, the presence of nonalcoholic fatty liver disease was associated with an increased risk for type 2 diabetes, and improvement in the disease over a 10-year follow-up period appeared to reduce the risk.

In the French study, nonalcoholic fatty liver disease was found to be a predictor of carotid atherosclerosis, independent of the classic cardiovascular risk factors. In patients with nonalcoholic fatty liver disease, carotid intima-media thickness (C-IMT), carotid plaques, and Framingham scores were greater.

Type 2 Diabetes

In the Japanese study, 3074 patients who did not have diabetes or hepatitis A or B and who did not consume excessive amounts of alcohol underwent 2 ultrasound health checks at least 10 years apart.

At baseline, 24% of the cohort was found to have nonalcoholic fatty liver disease, said Hajime Yamazaki, MD, from the Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan, who presented the results.

At a mean follow-up of 11.3 years, 16.1% of the 728 patients with nonalcoholic fatty liver disease at baseline had developed type 2 diabetes, compared with just 3.1% of the 2346 who did not. The crude odds ratio for the association was 6.05 (P < .001).

After multivariate analysis adjusted for a variety of confounders, including age, sex, body mass index, family history of diabetes, and dyslipidemia, the odds ratio remained significant, at 2.82 (P < .001).

Follow-up ultrasound showed improvement in 110 of the patients with nonalcoholic fatty liver disease at baseline; in the other 618, there was no improvement.

The reason for the improvement could not be determined from these data, but in most cases, it was likely the result of lifestyle changes, Dr. Yamazaki explained.

The incidence of type 2 diabetes lower in those whose condition improved than in those whose condition did not (6.4% vs 17.8%). The crude odds ratio for improvement in nonalcoholic fatty liver disease and type 2 diabetes was 0.31 (P = .004); on multivariate analysis, it was 0.30 (P = .003).

"The clinical message is that it is important to reduce fatty liver to prevent diabetes," he told Medscape Medical News.

This study is the largest and longest to show an association between nonalcoholic fatty liver disease and type 2 diabetes, and the first-ever to show a reduction in type 2 diabetes with improvement in fatty liver disease, he said.

This study was possible because ultrasound health checks are part of clinical practice in East Asian countries. It is unlikely that this type of study could be conducted elsewhere, but results would probably be similar in other populations, he explained.

Although cause and effect couldn't be assessed in this study, "for many of the patients — maybe for the majority — there is a causal link between liver disease and diabetes because the liver plays a central role in glucose homeostasis," Dr. Lammert pointed out.

Cardiovascular Disease

Results from the 2-part cross-sectional and longitudinal French study were presented by Raluca Pais, MD, PhD, from Université Pierre et Marie Curie and Hôpital de La Pitié-Salpêtrière in Paris.

The cross-sectional part involved 5671 patients 20 to 75 years of age who had 2 or more cardiovascular risk factors. All had undergone at least 1 carotid ultrasound to measure C-IMT and carotid plaques.

C-IMT was significantly higher in the 1871 subjects with nonalcoholic fatty liver disease than in the 3800 without the disease (0.64 vs 0.61 mm; P < .001), as were the prevalence of carotid plaques (44% vs 37%; P < 0.001) and Framingham risk scores (15 vs 8; P < 0.001). All were independent of age, sex, body mass index, hypertension, and tobacco use, Dr. Pais reported.

At 8-year follow-up in a subset of 1872 patients who had at least 2 C-IMT measurements, those with nonalcoholic fatty liver disease at baseline had a 34% increased risk for carotid plaques (P < .02).

These associations held true regardless of serum alanine aminotransferase levels, she said.

"Patients at risk for CVD should probably be screened for fatty liver, regardless of the transaminase levels, because nonalcoholic fatty liver disease is an independent predictor of cardiovascular risk, beyond traditional risk factors like metabolic syndrome," she told Medscape Medical News. "We don't know if nonalcoholic fatty liver disease is a marker or actively involved in the pathogenesis and progression of cardiovascular disease. It's at least a marker; for the rest, we don't yet have the answer."

Clinical Implications

During the briefing, Dr. Lammert advised that patients who enter a liver unit be assessed for cardiovascular risk and that those seen in cardiology settings be evaluated by a liver specialist.

"We should stratify the risk and define the subgroup of patients who would benefit from being treated by both a cardiologist and a hepatologist. It shouldn't happen by chance," he said.

He also advised that liver specialists focus on patients who present with nonalcoholic fatty liver disease without traditional cardiovascular risk factors, noting that at least 1 such genetic subgroup has been identified. "We need to define this better," said Dr. Lammert.

Dr. Yamazaki, Dr. Pais, and Dr. Lammert have disclosed no relevant financial relationships.

European Association for the Study of the Liver (EASL) International Liver Congress 2014: Abstracts 23 and 26. Presented April 10, 2014.


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