NASH Indications Increasing Amongst Patients in Need of a Liver Transplant

Zobair M. Younossi, MD, MPH

Nonalcoholic steatohepatitis (NASH) indications are increasing sharply for patients in need of a liver transplant.

A team, led by Zobair M. Younossi, MD, MPH, Betty and Guy Beatty Center for Integrated Research, Inova Health System, assessed liver transplant listing trends using chronic liver disease (CDL) etiology.

In the study, the investigators selected adult candidates for liver transplantation from the Scientific Registry of Transplant Recipients from 2002-2019.

The investigators calculated proportion trends for common CLD etiologies at the time of placement on the transplant wait list, including chronic infection with the hepatitis B virus, chronic infection with the hepatitis C virus (HCV), NASH, including cryptogenic cirrhosis, alcohol-related liver disease (ALD) with or without chronic HCV infection, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, in patients with and without hepatocellular carcinoma (HCC).

With a total 168,441 patients with known etiology and non-acute liver failure on the transplant waitlist, 27,799 patients (16.5%) had HCC.

However, in 2002 the most common etiologies in patients without HCC were chronic HCV infections (37%) and ALD (16%), while only 5% had NASH. For the patients with HCC, 58% had chronic HCV infections and 10% had ALD. On the other hand, only 1% had NASH in 2002.

For the 2019 data, among patients without HCC, NASH was the second leading indication for liver transplantation *28%), lagging behind ALD (38%).

For the patients with HCC, chronic HCV infection remained the leading indication (40%)/ However, NASH indications (24%) were higher than ALD (16%).

The investigators also found NASH was the leading indication for women without HCC (34%), patients over the age of 54 (36%), and patients on Medicare (41%).

In a trend analysis, investigators identified NASH as the most rapidly increasing indication for liver transplantation in patients without HCC (Kendall tau = 0.97; P <0.001), as well as in patients with HCC (tau = 0.94; P <0.0001).

One common issue for NASH is that it is difficult to diagnose without a liver biopsy.

Recently, a team, led by Theodore C. Friedman, MD, PhD, Charles R. Drew University of Medicine and Science, compared 3 non-invasive methods for identifying NASH using data from NHANES III (1988-1994) to determine variables associated with published formulas to identify the disease in data planned to be presented at ENDO 2020, the Endocrine Society’s annual meeting.

NASH is considered a serious liver disease that is marked by hepatic steatosis, cell damage, and inflammation, while increasing the risk of developing cirrhosis and hepatic cancer. Currently, NASH is diagnosed with a liver biopsy, which is both expensive and risky to the patient.

The investigators used ultrasound data to identify patients with moderate-to-severe hepatic steatosis. Furthermore, they identified the NASH population among those with hepatic steatosis using either the HAIR score, the NASH liver fat score, or the Gholam score.

The team developed the HAIR score in a sample of obese patients based on hypertension, insulin resistance, and alanine transaminase (ALT) levels. This method had an AUROC of 0.9, a sensitivity of 0.8, and a specificity of 0.89.

They also developed the NASH liver fat score in a Finnish population undergoing gastric bypass and validated this score in an Italian population of liver biopsy patients. The NASH liver fat score incorporates metabolic syndrome, type 2 diabetes, serum insulin, AST, and ALT.

By examining different trends regarding NASH prevalence, clinicians might also be able to improve diagnosis.

“In an analysis of data from the Scientific Registry of Transplant Recipients (2002 through 2019), we found NASH to be the second most common indication for liver transplant in 2019, and the fastest increasing indication,” the authors wrote. “In 2019, NASH was the leading indication for liver transplantation among women without HCC.”

According to experts, the profile of chronic liver disease has changed in the US, largely due to obesity changes and advancements in viral hepatitis treatment.

The study, “Nonalcoholic Steatohepatitis is the Most Rapidly Increasing Indication for Liver Transplantation in the United States,” was published online in Clinical Gastroenterology and Hepatology.