Editor’s Note:
On November 11, 2023, at the American Association for the Study of Liver Diseases annual meeting (AASLD 2023), the results of China’s first international registered randomized controlled trial (RCT) evaluating therapeutic efficacy through liver histology, known as the VENS study, were showcased in poster format. This presentation garnered significant attention and discussions from international experts in liver diseases. The conference brought together leading global experts in clinical hepatology, liver transplantation, and hepatobiliary surgery to advance clinical research and practices, providing optimal treatment guidance for liver and biliary disease patients.
Dr. Junping Shi from Hangzhou Normal University Affiliated Hospital led the VENS clinical trial. At the conference, he presented the latest research findings on the use of oral medium-dose vitamin E (300 mg/day) in the treatment of patients with nonalcoholic steatohepatitis (NASH) under the title “Vitamin E (300mg) versus Placebo in the Treatment of Nonalcoholic Steatohepatitis: a Multicenter, Randomized, Double-blind, Placebo-controlled Study” (VENS). Dr. Jie Li from Nanjing Drum Tower Hospital, one of the corresponding authors, participated in the offline meeting in Boston, showcasing Chinese data to the world.
In the VENS study, a total of 124 patients were randomly assigned to receive natural vitamin E (Livzon®) (58 patients) or a placebo (66 patients). In the modified intention-to-treat (ITT) population, 29.3% of patients receiving vitamin E showed histological improvement (43.6% per-protocol set [PPS]), compared to 14.1% in the placebo group (PPS 17.7%) (modified ITT P-value 0.040, PPS P-value 0.0071), as detailed in Figure 1. The proportion of reported severe adverse events was similar in both groups and considered unrelated to treatment. According to the final results, Professor Shi Junping, the principal investigator of VENS, concluded that oral administration of 300 mg/day natural vitamin E is a safe and effective foundational treatment for Chinese NASH patients.
Figure 1: Improvement in Liver Histology and Fibrosis Improvement Without NASH Deterioration
Note: The primary endpoint of the study was improvement in liver histology 96 weeks after treatment. Histological improvement was defined based on criteria such as NAS improvement by at least 2 points or NAS improvement of 3 points or less after treatment; an increase of at least 1 point in ballooning or inflammation score; and no worsening of fibrosis stage. The confirmatory secondary endpoint was improvement in liver fibrosis by at least 1 stage with no deterioration in NASH (defined as no increase in NAS due to fat, inflammation, or ballooning).*
Additionally, Dr. Junping Shi noted that the VENS clinical trial lasted for over 5 years, overcoming the challenges posed by the COVID-19 pandemic to achieve favorable results. During the trial, researchers utilized a mobile app to record patients’ lifestyles and closely monitored the safety aspects related to the prostate in male participants. Importantly, the study suggested that a lower dose (300 mg) of vitamin E, compared to the PIVENS study’s 800 IU (534 mg), still yielded positive outcomes for Chinese patients, addressing some clinical concerns about dosage.
According to the latest epidemiological data, the prevalence of nonalcoholic fatty liver disease (NAFLD) in mainland China has reached 30%, with over 300 million affected individuals, making NAFLD a significant concern in the country’s liver disease landscape. Currently, no drug has been approved globally for the treatment of NASH, making the clinical trial data from this study a beacon of hope for NASH patients and a new option for healthcare professionals.
