Chronic Liver Disease, Drug Induced Liver Injury
Conditions
Brief summary
DILI is an underdiagnosed and under appreciated causal or contributing factor to liver injury. DILI can mimics features of the entire spectrum of acute and chronic liver disease. Asia-Pacifc region is characterized by two unique features; the high prevalence of tuberculosis (TB) in the population and the ubiquitous use of traditional and complimentary medicines.Current definition of Hy's law presents significant difficulties when dealing with patients with preexisting CLD in clinical trials. Hallmark of the hepatic manifestation in these patients is hyperbilirubinemia and coagulopathy rather than ALT elevation.
Detailed description
Study Design Single-center, non-blinded, parallel group, randomized controlled trial. Allocation ratio between two groups: 1:1. Study population: Adults aged 18-75 years with previously known or unknown underlying CLD Diagnosis of DILI-based causality of assessment by RECAM. Severe DILI with bilirubin \> 12mg/dl or INR\>2, S.Bili \>5 mg/dl Consent to participate in the study (based on biopsy, imaging or clinical criteria). Study design: RCT Study period: 1 year Sample size: 96 Intervention: Patients after screening for all exclusion criteria will be randomized into either the standard treatment group or the plasma exchange group. Monitoring and assessment: All patients would undergo vital and baseline parameter screening before randomization. Based on randomization they will receive either steroid or plasma exchange followed by steroid.
Interventions
BIOLOGICALHigh volume Plasma Exchange
High volume Plasma Exchange with minimum 3 sessions on alternate days
OTHERStandard Medical Treatment
Standard Medical Treatment includes stopping the offending drug,nutrition,injection NAC,Tablet UDCA,steroid in DILI AIH
Sponsors
Institute of Liver and Biliary Sciences, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Adults aged 18-75 years with previously known or unknown underlying CLD. 2. Diagnosis of DILI based causality of assessment by RECAM. 3. Severe DILI with bilirubin \> 12mg/dl or INR\>2, S.Bili \>5 mg/dl. 4. Consent to participate in the study (based on biopsy/imaging/or clinical criteria).
Exclusion criteria
1. Active infection 2. Contraindications to plasmapheresis (e.g., severe coagulopathy, hemodynamic instability, patients with sepsis, shock, poor P/F ratio). 3. Pregnant or breastfeeding women. 4. HCC or any malignancy 5. UGI bleed, uncontrolled HE 6. Option LTx being considered 7. S. Creatinine \> 2mg/dL 8. DILI ALF 9. Alcoholic Hepatitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Liver Transplant free survival at the end of 30 days between two groups. | 30 days |
Secondary
| Measure | Time frame |
|---|---|
| Changes in arterial lactate levels, on lactate clearance at 0, 3, 5 days | 0, 3, 5 days |
| Reduction in von Willebrand factor levels, endothelial function, and coagulopathy at 0 and 30 day. | 0 and 30 day. |
| Changes in the inflammatory milieu, IL6, IL10, and TNF alpha at 0 and 30 day. | 0 and 30 day. |
| Change in liver-related decompensation events (ascites, HE, variceal bleed) at 0, 3, 5,30, and 90 days. | 0, 3, 5,30, and 90 days. |
| Change in serum bilirubin and bile acids clearance at 0, 3, 5,30 and 90 days. | 0, 3, 5,30 and 90 days. |
Countries
India
Contacts
Primary ContactDr Khushboo Yadav, MD
Backup ContactDr Shasthry SM, DM
Outcome results
None listed