Neil Osterweil

November 16, 2016

BOSTON — Over the past 2 decades, rates of nonalcoholic steatohepatitis (NASH) have increased fourfold in adolescents in the United States, and obesity rates have more than doubled, new research shows.

"Fortunately, the prevalence of advanced fibrosis remains low," said Praveen Kumar Conjeevaram Selvakumar, MD, from the Cleveland Clinic Children's Hospital in Ohio.

"However, it should be noted that we found a significant increase in the prevalence of advanced fibrosis from fatty liver disease among the Mexican-American adolescent population," he said here at The Liver Meeting 2016.

"In fact, being Mexican-American increased the risk of having advanced fibrosis from fatty liver disease by more than twentyfold in our study," Dr Selvakumar reported.

He and his colleagues used the National Health and Nutrition Examination Survey to look at trends in nonalcoholic fatty liver disease (NAFLD) in general, and NASH in particular, in adolescents 12 to 18 years of age in the United States. To estimate trends in suspected NASH and advanced fibrosis in adolescents, the team looked at three time periods: 1988 to 1994, 1999 to 2004, and 2005 to 2010.

To estimate the prevalence of NASH, the researchers used the Pediatric NASH Predictive Model. To calculate the probability of advanced fibrosis, they used the Pediatric NAFLD Fibrosis Score, which assesses alanine aminotransferase, alkaline phosphatase, platelet counts, and gamma-glutamyl transferase levels.

NASH was defined as the presence of NAFLD and a Pediatric NASH Predictive Model score of at least 75. Advanced fibrosis was defined as the presence of NAFLD and a Pediatric NAFLD Fibrosis Score of at least 8.

The 1988 to 1994 cohort consisted of 561 adolescents, which is equivalent to a weighted total of 1,705,960. The 1999 to 2004 cohort consisted of 5427 adolescents (weighted total, 8,317,271), and the 2005 to 2010 cohort consisted of 3551 adolescents (weighted total, 8,423,116).

In each cohort, approximately two-thirds of the adolescents were non-Hispanic white, about 15% were non-Hispanic black, and roughly 10% were Mexican-American.

Obesity was defined as a body mass index (BMI) in the ninety-fifth percentile, and severe obesity was defined as a BMI in the ninety-ninth percentile.

Table 1. Prevalence of Obesity

Body Mass Index 1988–1994, % 1999–2004, % 2005–2010, % P Value
Obese 9.10 16.60 18.90 <.001
Severely obese 0.81 3.30 5.00 <.001

 

On multivariable analysis, age was a risk factor for NASH in overweight or obese adolescents; every additional year was associated with an odds ratio (OR) of 1.2 (P < .001). In addition, risk for NASH was higher in males than in females (OR, 1.4; P < .001) and in Mexican-American than in non-Hispanic white adolescents (OR, 1.4; P = .005). Higher BMI percentile was also a risk factor for NASH (OR, 2.4; P < .001).

However, risk was lower in non-Hispanic black than in non-Hispanic white adolescents (OR, 0.50; P < .001).

Factors significantly associated with risk for advanced fibrosis in overweight or obese adolescents were higher BMI percentile (OR, 6.7; P = .003) and being of Mexican-American descent (OR, 20.5; = .003).

Table 2. Significant Increases Over Time in Liver Disease

Adolescent Group 1988–1994, % 1999–2004, % 2005–2010, % P Value
Suspected NAFLD        
   All 3.30 8.80 10.10 <.001
   Male 5.50 12.10 14.40 .001
   Female 1.40 5.30 5.60 .016
   Non-Hispanic white 3.30 7.70 9.00 .025
   Non-Hispanic black 1.40 6.50 8.60 <.001
Suspected NASH        
   All 0.74 3.10 3.40 .008
   Male 0.73 4.20 4.70 .009
   Non-Hispanic white 0.46 2.40 3.10 .01
Suspected advanced fibrosis        
   Mexican-American 0.00 0.61 1.40 .005

 

"Needless to say, NALFD should be diagnosed earlier and efforts such as exercise and healthy diet should be instituted earlier to prevent complications from happening," Dr Selvakumar said.

Getting patients to change their lifestyle habits on the basis of future risk for liver disease can be a hard sell, he acknowledged.

"When patients come to our clinic, they do not understand the implications of this disease because they are asymptomatic," he told Medscape Medical News. "These findings can help us to talk with them," he said, and explain that "this is the most common cause of liver transplantation in adults."

Concerned, But Not Surprised

The findings from this study are concerning but not surprising, said Kimberly Brown, MD, a specialist in clinical and transplant hepatology at the Henry Ford Hospital in Detroit, who was not involved in the study.

"We are seeing more and more young adults with NAFLD and NASH, and the assumption is that they acquired the disease or became at risk as adolescents, which is very concerning," she told Medscape Medical News. In addition, "we see patients in their twenties who already have fibrosis or cirrhosis or other complications of their metabolic illness."

On the basis of the prevalence of NASH in adults, clinicians in the United States can expect to see an additional 800,000 to 900,000 cases of hepatocellular carcinoma in the future, which is a very conservative estimate, she reported.

"Last year, we did a little over 7000 transplants; that is our treatment right now for liver cancer," Dr Brown explained.

"Right now, although the incidence of this cancer is relatively low, the numbers of patients at risk make that total number at the end just huge, and something that we're going to find very difficult to manage," she pointed out.

The study funding source was not disclosed. Dr Selvakumar and Dr Brown report no relevant financial relationships.

The Liver Meeting 2016: American Association for the Study of Liver Diseases (AASLD): Abstract 202. Presented November 14, 2016.

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