With significant advances in the treatment of viral hepatitis—including increasing cure rates for hepatitis C and highly effective treatment of hepatitis B—suspicions have arisen that the profile of liver disease in the United States will change, explains Zobair M. Younossi MD, MPH. “The liver disease associated with obesity and diabetes is non-alcoholic fatty liver disease (NAFLD), and thus it has been hypothesized that, as viral hepatitis B and C are being treated more effectively and the rates of obesity are increasing, and the fact also that there is no treatment for NAFLD, that rates of NAFLD will increase,” he adds. “Given this, it’s important for to understand the type of liver disease burden to expect over the next few decades.”

Confirming Suspicions

To assess the shift in the prevalence of different live disease etiologies (chronic hepatitis B, hepatitis C, alcoholic liver disease, and NAFLD) over the past 3 decades, Dr. Younossi and colleagues assessed prevalence data among more than 58,000 NHANES  participants during 1988-1994, 1999-2004, 2009-2012, and 2013-2016. Their results were published in Gut.

“We found that, over these time periods, the only liver disease that increased in prevalence was NAFLD, from 20% in 1998-1994 to 32% in 2013-2016 (Figure),” says Dr. Younossi. “The prevalence of hepatitis C actually decreased over time, while the prevalence rates of hepatitis B and alcoholic liver disease remained stable.” During the same period, steady increases were observed in rates of obesity (from 22.2% to 38.9%), type 2 diabetes (from 7.2% to 13.5%), insulin resistance, and hypertension.

“When we assessed the drivers of increasing NAFLD prevalence by running a multivariable regression analysis and controlling for all potential confounders, it was clearly shown that obesity and type 2 diabetes were two major, independent predictors of NAFLD,” notes Dr. Younossi. “We think, and believe it’s been confirmed, that the rates of increase in obesity and type 2 diabetes lead to another complication, and that’s an increasing rate of NAFLD.”

Important Considerations

Dr. Younossi explains that there are important factors associated with the increased prevalence of NAFLD for physicians to consider, among them that the disease may be more prevalence in Hispanic Americans, when compared with Caucasians and African Americans. “Also, although obesity and type 2 diabetes are the strongest drivers of NAFLD, other metabolic conditions play a role, specifically high cholesterol and high blood pressure. These four conditions—obesity, type 2 diabetes, high cholesterol, and hypertension pressure—make up metabolic syndrome, of which NALFD is a liver complication.”

Because of the prevalence of NAFLD and potential for encountering a patient with the disease, Dr. Younossi recommends that primary care physicians, cardiologists, endocrinologists, gastroenterologists, and other specialists understand that NAFLD is “going to become the most common liver disease in the US, as well as that some patients with NAFLD will have non-alcoholic steatohepatitis (NASH) and can potentially progress to cirrhosis. In fact, NASH is now one of the most common indications for liver transplantation, especially in women, an important cause of liver cancer, and negatively impact quality of life and other patient-reported outcomes.”

Dr. Younossi notes the need for more research to better understand which patients with NAFLD will progress to NASH. “It’s important to have an accurate, noninvasive test, because NASH is currently diagnosed via liver biopsy,” he adds. “We also need better treatment; we currently only have lifestyle modification with exercise and diet. With medical treatment becoming available in the future, knowing exactly which patients should be treated with the addition of medication versus only lifestyle modification is something we’re looking forward to.” In the meantime, Dr. Younossi calls for increased awareness among physicians of NAFLD as an important complication of metabolic syndrome.