Intravenous BCAA for HE in ACLF (BCAA-HE-ACLF)

Intravenous Branched-chain Amino Acids for Overt Hepatic Encephalopathy in Patients With Acute on Chronic Liver Failure - A Multi-centric Double-blind Randomized Controlled Trial

Amrita Institute of Medical Sciences & Research Center, Asian Institute of Gastroenterology, India, All India Institute of Medical Sciences, Bhubaneswar, Kalinga Institute of Medical Sciences, Bhubaneswar

This multi-centric study analyses the effect of intravenous branched-chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators aim to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone, ammonia measures, endotoxin, metabolomics, and cerebral edema in the medical management of overt HE in patients with ACLF. The study will also access the impact on overall survival and improvement in the grade of HE.

Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients with HE. The mainstay of treatment remains Lactulose. Rifaximin is added on to therapy who have a breakthrough episode of HE on lactulose. BCAA is used as an add-on therapy if patients have minimal/covert encephalopathy, are protein intolerant or have recurrent HE. No studies are available assessing the adjuvant effect of intravenous BCAA on ammonia reduction in HE in patients with ACLF. So, this study has been designed to analyze the effect of intravenous BCAA on hepatic encephalopathy in patients with ACLF. This study will also analyze the systemic and neuronal inflammation, metabolomics, and cerebral edema under the effect of intravenous BCAA in HE patients with ACLF.

Hepatic Encephalopathy, Acute-On-Chronic Liver Failure, Neurological Dysfunction, Metabolomics, Systemic Inflammations, Branch Chain Amino Acid, bispectral index, Cerebral edema, Lactulose

Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose

Dynamic Assessment of systemic inflammation (Cytokines: IL-1b, IL-6, INF-g, TNF-a, IL-15, IL-17, IL-18) at presentation and after Specific management.

Inclusion Criteria: Age 18-75 years Either gender Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria Exclusion Criteria: Those who do not consent to participate in the study Patients with structural brain lesions or stroke Inability to obtain informed consent from patient or relatives Severe preexisting cardiopulmonary disease Renal dysfunction (S. Creatinine ≥ 2mg/dL) Pregnancy/Lactation Post liver transplant patients HIV infection Patients who are on psychoactive drugs, like sedatives or antidepressants Patients who are too sick to carry out the protocol.

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