10.20.2015

Two-thirds of treated patients had decreases in alanine aminotransferase

by Nancy Walsh
Senior Staff Writer, MedPage Today

HONOLULU — Treatment of nonalcoholic steatohepatitis (NASH) with vitamin E and pentoxifylline led to improvements in liver enzymes, a real-world study found.

In a study that included 106 patients given NASH-specific therapy, those in the treatment group had median decreases in alanine aminotransferase (ALT) of 58.4% (95% CI 40.6-75.2) compared with a decline of 42.7% (95% CI 11.9-63.8) in the no-treatment group (P=0.029), reported Naim Alkhouri, MD, of the Cleveland Clinic in a poster session at the American College of Gastroenterology meeting here.

The incidence of NASH — a potentially lethal condition — has been rising rapidly worldwide, and today is the most common liver disease. The current mainstay of treatment is lifestyle modification focused on diet and exercise.

“Weight loss can actually help in NASH, as has been shown in studies of bariatric surgery where patients had biopsies at the time of surgery and 1 year later showing a resolution of the NASH and in some cases improvements in fibrosis. Also, if patients lost 7% to 10% of their body weight, it improved the histologic features of NASH,” he said.

“But lifestyle modification is successful only in a minority of patients — about 5% to 10%, and we still don’t have any FDA-approved treatments for NASH, which is the aggressive form of fatty liver disease,” he said.

Previous randomized studies of the antioxidant vitamin E and pentoxifylline have demonstrated some benefits in NASH, but concerns have been raised about the efficacy and potential for adverse events with these therapies and the data thus far are very limited.

For instance, in a randomized NIH-sponsored study published in the New England Journal of Medicine that included 247 adults with NASH to vitamin E (800 IU/day), pioglitazone (30 mg/day), or placebo, improvements in histologic findings and disease activity scores were seen in 43% of the vitamin E group compared with 19% of the placebo group. Liver enzymes also improved in with vitamin E treatment.

“For pentoxifylline, we only have small phase II studies and larger studies are needed. Furthermore, these agents have not shown effects on hepatic fibrosis, which is the holy grail of treatment for any liver disease, so hepatologists have been waiting for more effective treatments,” Alkhouri said in an interview.

“Nonetheless, vitamin E has been shown to help with NASH resolution and may help with decreasing liver enzymes, and in one small study pentoxifylline has shown mild improvement in hepatic fibrosis.”

To assess the efficacy of these treatments in a tertiary care setting, Alkhouri and colleagues enrolled adults who had been diagnosed with NASH based on imaging studies showing fatty infiltration of the liver with ALT levels above 60 U/L on two occasions, or liver biopsy showing histologic findings typical of NASH.

Initially all were instructed to follow the Mediterranean diet and were advised on other lifestyle modifications.

Patients were divided into a treatment group, in which they were given 400 IU of vitamin E twice daily plus pentoxifylline 400 mg three times per day if no improvement in ALT occurred by 6 months, or to a group receiving no NASH-specific therapy. All patients in the treatment group had a baseline liver biopsy, as did 92% of those in the no-treatment group. The primary outcome was change in ALT levels, as repeat biopsies were not done on all patients.

The treatment group included 33 patients, while the no-treatment group consisted of 73 patients. Among those in the treatment group, 17 remained on vitamin E monotherapy while 16 also received pentoxifylline.

Patients in the treatment group were older than those in the no-treatment group (53.5 versus 48.6 years, P=0.043), and had higher nonalcoholic fatty liver disease activity scores on biopsy (5.4 versus 4.4, P<0.001).

The two groups were similar in patient body mass index, the prevalence of hypertension and diabetes, hemoglobin A1c levels, and baseline ALT.

During a median follow-up of 2.3 years, more than two-thirds of patients in the treatment group (69.7%) showed normalized ALT levels of below 45 U/L or less than 50% of the baseline level, compared with only 53.4% of patients in the no-treatment group.