Methylprednisolone + standard care may reduce HBV-ACLF–related mortality

The addition of methylprednisolone to standard care* reduced mortality risk in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), according to a study from China.

HBV-ACLF accounts for about 70 percent of ACLF cases in Asia, and is the most common type of liver failure, said the researchers. While liver transplant is the only cure that has proven to work, its use is limited by the rapid progression of the disease as well as a lack of donors, they said.

“In this study, we found that methylprednisolone improved the efficacy of standard treatment in HBV-ACLF, [suggesting it] could be a safe and effective treatment for [this condition],” they noted.

Study participants were 171 adults (mean age 45.2 years, 88.9 percent male) with HBsAg-positive HBV-ACLF recruited from three medical centres in China between April 2013 and May 2015. They were randomized 1:1 to receive intravenous methylprednisolone for 7 days at a tapered dose (1.5 mg/kg/day on days 1–3, 1 mg/kg/day on days 4–5, and 0.5 mg/kg/day on days 6–7) plus standard care or standard care alone.

About 81 percent of patients had cirrhosis at enrolment, 87.7 percent had detectable HBV DNA (≥100 copies/mL), and 52.6 percent were HBeAg-positive. Eighty-three percent (n=142) completed 6-month follow-up. Receipt of standard treatment was comparable between groups.

Patients who received methylprednisolone had a significantly lower mortality rate at 6 months than those on standard care alone (32.4 percent vs 42.5 percent; p=0.0037). [BMC Med 2020;doi:10.1186/s12916-020-01814-4]

Of the 88 total deaths, a majority (43.2 percent) occurred before day 30. Cause of death, including infection, did not significantly differ between groups.

Treatment with methylprednisolone was an independent predictor of survival at 6 months (hazard ratio [HR], 0.547, 95 percent confidence interval [CI], 0.308–0.973; p=0.040). Among methylprednisolone-treated patients, HBV DNA positivity (HR, 4.875, 95 percent CI, 1.596–14.889; p=0.005) and lymphocyte-to-monocyte ratio (HR, 0.537, 95 percent CI, 0.291–0.992; p=0.047) were predictors of reduced mortality at 6 months.

One and eight patients in the methylprednisolone and standard care groups, respectively, underwent liver transplantation. HBV DNA replication did not significantly differ between groups.

There was a significant improvement in mortality when patients with early ACLF were treated with methylprednisolone vs standard care (eg, HR, 3.981; p=0.027 at 30 days and HR, 2.658; p=0.048 at 120 days).

Patients in the methylprednisolone group were more likely to experience hypoalbuminemia (56.6 percent vs 37.5 percent; p=0.012), fungal infections (32.5 percent vs 19.3 percent; p=0.048), and ascites (33.7 percent vs 20.5 percent; p=0.050) than those in the standard care group. Incidence of new onset infection was comparable between groups (41.0 percent vs 31.8 percent; p= 0.214), as was incidence of electrolyte disturbance, hepatorenal syndrome, gastrointestinal haemorrhage, acute renal insufficiency, hypoglycaemia, pleural effusion, adrenal hyperplasia, and peptic ulcer.

Research suggests that an inflammatory cascade occurs in the early stages of HBV-ACLF, with earlier systemic inflammatory response syndromes corresponding with increased mortality rates, the researchers said.

“Methylprednisolone can stabilize hepatocyte membranes, suppress inflammation, and prevent further necrosis of hepatocytes. Therefore, early application of methylprednisolone therapy can suppress immune response,” they suggested. This inhibition of inflammation could delay disease progression and improve survival, they added.