麻豆传媒

More effective treatments for alcoholic hepatitis are urgently needed, according to a , which showed that there has been no improved survival in the past 40 years and even indicated some evidence of a decline.

"There has been ongoing research for many years in alcoholic hepatitis, and many therapeutic agents have been examined for efficacy," Richard Parker, MBChB, of the University of Birmingham in England, and colleagues wrote in PLoS ONE. "However, our data show that mortality from alcoholic hepatitis has not improved over more than 4 decades. Indeed we found a small but significant increase in mortality at 180 days."

The lack of improvement was not explained by changes in disease severity, underscoring a pressing need to develop better treatments, the authors stated.

The systematic literature search identified randomized controlled trials and observational studies and extracted data on 28-day, 90-day, and 180-day mortality post-hospitalization, as well as biochemical and clinical information. The 77 eligible studies, published during 1971-2016, included a total of 8,184 patients.

When all studies were considered, the average mortality rate from alcoholic hepatitis was 25% at 28 days after admission and 29% at 90 days after admission. No clear changes in mortality over time emerged in univariable analysis at either 28 or 90 days after hospitalization (Pearson correlation r=-0.216, P=0.098, and r=0.121, P=0.503, respectively). At 180 days after admission, mortality averaged 44%.

Although a small but statistically significant increase in mortality was seen in 180-day mortality (r=0.461, P=0.036), this was likely a product of the paucity of trials reporting this longer outcome in the 1970s, the authors explained. After meta-regression to adjust for other mortality-linked factors at each time point, no changes in mortality emerged. In addition, subgroup analysis revealed no changes in mortality over time across different study types or with the consideration only of biopsy-proven or severe disease.

The lack of change also held when the authors considered only therapeutic trials, in which inclusion and exclusion criteria were likely more stringent. When intervention and control group studies were assessed separately, a small but statistically significant improvement in 28-day mortality was seen in the control groups (r=-0.341, P=0.034).

Creatinine, bilirubin, white cell count, and age were all factors associated with mortality and showed some change over time.

Asked for her perspective, Jessica L. Mellinger, MD, of the University of Michigan, Ann Arbor, who was not involved with the study, said, "Unfortunately, there are few medical treatments to reverse alcoholic hepatitis, despite numerous studies. The findings that mortality has not improved over the years is therefore not surprising, given the lack of clearly beneficial treatments."

Although intensive care for these patients has improved over time and some studies have shown survival improvement, she said, "alcoholic hepatitis patients are frequently among the most critically ill patients, and more research is urgently needed to find new ways of treating alcoholic hepatitis. Stopping alcohol use is currently the only clearly proven way of improving mortality long-term, so every effort should be made to connect patients with alcohol-related liver disease to alcohol use treatment."

The Birmingham group's findings on mortality align with previous showing no survival improvement during 1968-1999 in discharged liver disease patients at 20 or 12 months, although those with alcoholic hepatitis fared better than those with decompensated cirrhosis. Increased mortality from accidents, suicides, and mental disorders -- particularly in cirrhotic alcoholics -- indicates the influence of behavioral as well as physical pathology on prognosis, the researchers said.

"While progress towards novel specific treatments in alcoholic hepatitis has been frustratingly slow, it might be expected that improvements in medical care of acutely unwell patients would have a positive effect on outcomes. Our results do not support this."

Parker and colleagues added, however, that since many alcoholic hepatitis patients present to non-specialist medical services, implementation of there may mean better treatment in the early stages of disease. "Equally important is the ongoing pursuit of better treatments for alcoholic hepatitis that may make a significant impact on outcomes. This is especially pertinent given the underwhelming evidence for the efficacy of corticosteroids." (麻豆传媒 previously reported on the lack of long-term survival benefit with the use of pentoxifylline or prednisolone in alcoholic hepatitis patients.)

In terms of study limitations, Parker and colleagues noted missing data, particularly for outcomes beyond 28 days, the dependence on aggregate reported data versus more reliable patient-specific data, and the lack of information on specific causes of death.

Comment