Miriam E. Tucker

May 01, 2015

VIENNA — In patients with nonalcoholic fatty liver disease, progression is accompanied by increases in the rates of cardiovascular disease burden and mortality, new research shows.

"The bottom line is that cardiovascular comorbidities, such as chronic kidney disease, stroke, and heart failure are extremely common in nonalcoholic fatty liver disease, and it appears that they may be more common in the more advanced stages of disease," said Jake Mann, MD, from the University of Cambridge in the United Kingdom.

"From our study, we can't prove this, but we found an increasing trend of association," Dr Mann told Medscape Medical News.

Dr Mann presented results from a 14-year analysis of hospital chart data here at the International Liver Congress 2015.

"You have to be cautious because with very large cohorts, there is bias, said Laurent Castera, MD, from Hôpital Beaujon in Clichy, France, who is vice-secretary of the European Association for the Study of the Liver.

"The message is important," he told Medscape Medical News. "Most of these patients die of cardiovascular disease rather than liver disease."

"In the post-hepatitis C era, fatty liver is the most important disease in the field of hepatology, so we need to increase the awareness of nonhepatologists," he added.

Most of these patients die of cardiovascular disease rather than liver disease.

Dr Mann and his team reviewed routinely collected data in the records of 929,465 patients from several hospitals in England from 2000 to 2013. Using diagnostic codes, the team identified 1294 patients with fatty liver disease, 122 with nonalcoholic steatohepatitis, and 1285 with cirrhosis.

In each of the three diagnostic groups, about 57% of the patients were male, about 79% were white, and about 11% were of Southeast Asian origin. Patients in the cirrhosis group were significantly older than those in the fatty liver and steatohepatitis groups (59.2 vs 50.6 vs 51.6; P < .0001).

During the 14-year study period, all-cause mortality was significantly lower in the fatty liver group than in the steatohepatitis group (14.5% vs 22.1%; P < .05) and the cirrhosis group (14.5% vs 53.1%; P < .0001).

In addition, the rate of congestive cardiac failure was significantly lower in the fatty liver group than in the steatohepatitis group (3.8% vs 9.0%; <.01) and the cirrhosis group (3.8% vs 6.6%; P < .001).

The rate of type 2 diabetes was significantly lower in the fatty liver group than in the cirrhosis group (20.9% vs 31.2%; P < .0001), as were rates of atrial fibrillation (4.9% vs 8.3%; P < .0001) and chronic kidney disease (3.1% vs 6.9%; P < .0001).

After adjustment for a variety of confounders — including age, sex, ethnic group, diabetes, heart failure, atrial fibrillation, myocardial infarction, cardiomyopathy, ischemic stroke, chronic kidney disease, peripheral vascular disease, and hypertension — the higher risk for mortality in the steatohepatitis group than in the fatty liver group was no longer significant (hazard ratio [HR], 1.5). However, the rate remained a significant 5 times higher in the cirrhosis group than in the fatty liver group (hazard ratio 5.1).

Although the mechanism isn't entirely clear, it appears that there are two general forces at work, Dr Mann explained. First, the traditional macrovascular risk factors — central obesity, insulin resistance, and dyslipidemia — appear to be both a cause and an exacerbation of fatty liver disease. Second, novel risk factors such as a systemic rise in inflammatory cytokines and impaired fibrinolysis might be more concentrated in steatohepatitis than in fatty liver disease.

In clinical practice, the distinction between fatty liver, steatohepatitis, and cirrhosis is often difficult to define. "The definitions are confusing even to hepatologists," he told Medscape Medical News.

"The only way you can be absolutely sure is if the patient has a biopsy. So it's best to consider all of these patients at high risk and manage along standard treatment algorithms, including statins for patients in appropriate risk categories," Dr Mann said.

Dr Mann has disclosed no relevant financial relationships. Dr Castera has served on the speaker's bureau for Echosens.

European Association for the Study of the Liver (EASL) International Liver Congress 2015: Abstract G-12. Presented April 24, 2015.


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