乌鸦传媒

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WASHINGTON -- Research presented here at the annual Liver Meeting sponsored by the American Association for the Study of Liver Diseases included a better combination for severe alcoholic hepatitis, real-world insights on normothermic machine perfusion for liver transplantation, and an app-based program for weight loss in nonalcoholic steatohepatitis (NASH).

Steroids Plus G-CSF in Severe Alcoholic Hepatitis

Adults with severe alcoholic hepatitis had better odds of surviving to 90 days if they received prednisolone with granulocyte-colony stimulating factor (G-CSF), according to a .

Survival at 90 days reached 88.1% with the combination, as compared to 64.3% with prednisolone monotherapy and 78.6% with G-CSF alone (P=0.03), reported Shiv Sarin, MD, of the Institute of Liver and Biliary Sciences in New Delhi, in a late-breaking presentation.

Rehospitalizations were lower with the combination (14.3% vs 59.5% and 31%, respectively), and responses based on Lille scores at 7 days were significantly improved in the prednisolone plus G-CSF arm (P=0.002).

"G-CSF, in our opinion, should be considered as an add-on therapy to improve the long-term outcome of prednisolone therapy," said Sarin.

Among 454 patients screened, the trial randomized 126 adults with severe alcoholic hepatitis (Maddrey's discriminant function [mDF] levels of 32-90) in a 1:1:1 ratio:

• Prednisolone (40 mg) and G-CSF (300 mcg) for 7 days, followed by G-CSF every 3 days
• Prednisolone monotherapy for 7 days
• G-CSF alone for 7 days, then every 3 days

Patients were quite sick, said Sarin, with bilirubin ranging from 22-23 mg/dL and an international normalized ratio of 1.82-1.92.

Average age was 40-43 years, mean Model for End-Stage Liver Disease (MELD) scores were 24-25, and mean mDF levels at baseline were 63-65. Patients were excluded if they had acute gastrointestinal bleeding, hepatorenal syndrome, or other forms of hepatitis.

At 28 days, survival was no different between the three treatment arms: 95.2% in the combination group, 85.7% in the prednisolone-monotherapy group, and 85.7% in the G-CSF-alone group (P=0.27).

For adverse events at day 90, acute kidney injury was significantly less frequent in the combination therapy arm (7.1% vs 31% with prednisolone and 9.5% with G-CSF), as was hepatic encephalopathy (9.5% vs 47.5% and 25%, respectively) and skin and mucosal bleeds (19% vs 25% and 35.7%).

Infections, meanwhile, occurred in 19% of patients on the combination therapy, 35.7% in the prednisolone-monotherapy group, and 7.1% of those on G-CSF alone.

Normothermic Machine Perfusion for Liver Transplantation

As early adopters, Michelle Nguyen, MD, of the Mayo Clinic in Scottsdale, Arizona, shared insights into how her center is benefiting from the liver normothermic machine perfusion system.

The high-volume center performs more than 200 liver transplants a year, and began using normothermic machine perfusion for both donation after brain death (DBD) and donation after circulatory death (DCD) livers within the last year.

In the 90 transplants performed between January and May 2022, the center was able to have a higher mean donor age when procuring livers with normothermic machine perfusion compared with standard static cold storage, both in cases where the livers were DBD (57 vs 46 years, respectively) or DCD (49 vs 39 years).

Total liver transplant operating time was shorter with normothermic machine perfusion (mean 253 vs 283 minutes with static cold storage; P=0.02), and pumped livers could also be preserved for longer periods of time (mean 11.7 vs 7.2 hours), which meant they could be transported from further away.

"We've been able to pursue organs as far as 1,500 miles away," Nguyen noted. "We've even pursued livers from as far away as Hawaii."

Normothermic mechanical liver perfusion was associated with a lower likelihood of early allograft dysfunction compared to static cold storage (35.4% vs 57.1%). In the DCD subgroup, early allograft dysfunction was also significantly less frequent (36.8 % vs 89.5%; P<0.001). Moreover, 30-day readmission was lower in pumped livers.

"We placed a 68-year-old DCD donor on the pump," she said. Furthermore, she noted that the center has been able to transplant DCD livers with over 30% macrosteatosis.

Nguyen acknowledged that the upfront cost was high with the normothermic machine perfusion system.

NASH and Noom Weight-Loss Program a Winning Pair?

A proof-of-concept study in patients with NASH, a severe form of nonalcoholic fatty liver disease (NAFLD), suggested a meaningful weight-loss benefit with Noom Weight, a smartphone app-delivered program that encourages lifestyle changes through nutrition education and motivational goal-setting.

In the randomized trial of 40 patients with NASH, three times as many patients had clinically significant weight loss at week 16 with Noom Weight (45% vs 15% with standard clinical care, P=0.038), Jonathan Stine, MD, of Penn State College of Medicine in Hershey, reported here in a poster presentation. Clinically significant weight loss was defined as 5% or more of a patient's body weight.

In NAFLD, every bit of body weight loss counts toward better outcomes, Stine explained, pointing out that loss of body weight also translates to loss of fat in the liver itself. "At 3-5% you see histologic change, at 7-10% scar tissue starts to heal," he told 乌鸦传媒.

"Despite many years of research for weight loss, many people with NAFLD still remain unsuccessful," said Stine, adding that the Noom Weight program mainly works on behavior and doesn't involve a lot of physical activity.

In the study, weight loss decreased by an average 5.4% in the investigational arm compared with 0.4% in the standard-care arm (P=0.004), with most of the loss occurring by week 12.

"Our pilot randomized controlled trial showed Noom was physically safe and highly efficacious in reducing body weight," said Stine, who said he hopes to conduct a larger study.

Patients in the study were matched by age (mean 50-53 years) and level of education, and all were white. Most had stage 2 fibrosis (50%), followed by stage 0/1 fibrosis in 40-45%, and stage 3 fibrosis in 5-10%.

Common comorbidities included diabetes, hyperlipidemia, and hypertension. There were five active or former smokers in the Noom arm and 10 in the standard-care arm.