जर्नल ऑफ क्लिनिकल एंड एक्सपेरिमेंटल फार्माकोलॉजी

अमूर्त

Efficacy of Thiamine and Medical Management in Treating Hyperuricemia in AUD Patients with ALD: Role of Hyperuricemia in Liver Injury, Gut-Barrier Dysfunction, and Inflammation

Vatsalya Vatsalya, Fengyuan Li, Jane Frimodig, Nihar Shah, Amar Sutrawe, Wenke Feng

Background: Hyperuricemia has been reported in liver injury; however its role in the early stage of Alcohol-associated Liver Disease (ALD) has not been examined yet. This study investigated the role of Serum Uric Acid (SUA) in alcohol-related liver disease, gut barrier dysfunction, and inflammation activity. This study also evaluated the efficacy of abstinence, treatment with thiamine and medical management to alleviate hyperuricemia.

Methods: 48 heavy drinking Alcohol Use Disorder (AUD) patients (34 males [M]/14 females [F]) participated in this study. Patients were grouped by serum Alanine Aminotransferase (ALT) levels as group 1 (ALT ≤ 40 U/L, 7M/8F) and group 2 (ALT>41U/L, 27M/6F). All patients received open label thiamine 200 mg daily dose. Demographics, drinking history (using Lifetime Drinking History [LTDH], and Timeline Follow Back TLFB] for the past 90 days) reports were collected at baseline. Baseline and three-week assessments for SUA, biomarkers of liver injury, endotoxemia and inflammation were evaluated.

Results: 22 out of 48 AUD patients reported hyperuricemia, primarily in males. SUA was significantly associated with ALT in each group (in group 2, when covaried with HDD90). SUA was also significantly associated with gut barrier dysfunction markers, LBP and LPS, in group 2, SUA and LBP predicted IL-1β significantly in group 2. Uric acid along with IL-1β and HDD90 significantly predicted necrotic type of hepatocyte cell death in group 2. Post-treatment SUA dropped across both the groups, significantly in females; adverse effects of drinking, cytokine and uric acid interaction on liver cell death also decreased in group 2. In vitro experiments validated the efficacy of thiamine on hepatocytic uric acid production in alcohol sensitization.

Conclusion: Uric acid, a metabolic risk signal, was likely involved in the interaction of proinflammatory activity with heavy drinking markers at early-stage ALD. Three-week inpatient medical management, along with treatment with thiamine, seems to alleviate baseline hyperuricemia and necrotic type of hepatocytic cell death in AUD patients with liver injury.