To Study the Clinical Course and Outcomes of Non-electively Hospitalised Patients of Chronic Liver Disease (CLD) With Hepatic or Extra-hepatic Predominant Organ Failure(s) at 6 Months.

Hypothesis: Liver failure predominant presentation, hepatic insult, index presentation, with or without subsequent EHOF are detected early with a better recovery and survival in absence of liver transplant due to a distinct immunologic, regenerative profile.

Aim - To study the clinical course and outcomes of non-electively hospitalised patient of chronic liver disease (CLD) and cirrhosis presenting with Hepatic or Extra-hepatic predominant organ failure(s) at 6 months.

Objectives-

Primary objective:

To study the survival outcomes among non-electively hospitalised patients of chronic liver disease (CLD) with Hepatic or Extra-hepatic predominant organ failure at 6 months.

Secondary objectives:

1.       Spectrum of clinical presentation, acute insult, etiology in both the groups, infections and complications.

2.       Chronology and sequence of organ failures (OF).

3.       To define and record the frequency of AD, NAD and further decompensation in 6 month follow up.

4.       To define the time frame for SIRS, Sepsis and development of new OF

5.       Identifying the patients and profile needing liver transplant in 6 months follow up.

6.       Therapy and its impact on readmission, survival without liver transplant.

7.       To define the patients as ACLF type-A (Hepatic failure predominant) and type-B (Extra-hepatic organ failure) predominant.

8.       Long-term survival, reversal, regression or Recompensation of CLD after acute presentation in relation to presentation with liver or EHOF predominant presentation at 6 month follow up.

9.       To study the immunologic (IL-1, IL-6, TNF -alpha, monocyte/macrophage, neutrophil and lymphocyte function), regeneration (HGF, EGF, AFP, IL-6), Extracellular vesicles (EVs) and proteomics at baseline, day 4 and day 7 for infection, new OF, or recovery prediction in subset of patients.

10.   Development and validation of AI based model for prediction of recovery, infection, need of LT or development of new organ failure.

Monitoring and assessment: The patient will be evaluated with detailed history, clinical examination, laboratory parameters, therapy offered, clinical course and survival. Evaluation for potential acute insults, including severe alcoholic hepatitis, reactivation of chronic hepatitis B, drug-induced liver injury, acute viral hepatitis (HAV, HEV), autoimmune hepatitis flare, and Wilson’s disease will be done. Diagnostic investigations will be tailored to each suspected condition. Acute alcoholic hepatitis will be diagnosed when chronic alcohol use is confirmed, alongside documented alcohol consumption within the last 8 weeks, and after excluding other acute insults like hepatitis A, B, C, or E based on serology and molecular testing. The possibility of hepatotoxicity from drugs, herbs, or indigenous remedies will be considered based on a detailed history and the temporal association of substance use with liver failure. Chronic liver disease workup will include assessing viral etiologies, autoimmune conditions, MAFLD/MASH, and cholestatic liver diseases (PSC, PBC, Overlap). The diagnosis of cirrhosis will be based on a composite of clinical signs and findings provided by laboratory test results, endoscopy, and radiologic imaging or liver biopsy findings, if available. In a proportion of patients, trans-jugular liver biopsy (TJLB) will be performed to establish the diagnosis and the etiology of acute and chronic insult. Hepatic encephalopathy was graded according to the West Haven classification. The disease severity scores (CTP, MELD Na, MELD 3.0, AARC, CLIF-C ACLF), Organ failures (hepatic, coagulation, cerebral, renal, circulatory and respiratory), complications (infection, variceal bleed, ascites) will be recorded. Patients will be closely monitored for the onset of sepsis and organ failure, with regular assessments of laboratory parameters and clinical status. Sepsis screening will be systematically conducted with blood and body fluid cultures, chest x-rays, and ascitic fluid analysis at baseline and on days 4, 7, and 15, or whenever clinically indicated. Sepsis management adhered to local antibiotic guidelines, tailored to microbial sensitivity patterns at each center. Patients with grade III/IV hepatic encephalopathy and respiratory failure will be managed with mechanical ventilation. Acute Kidney Injury (AKI) will be initially treated with terlipressin and albumin; if unresponsive, renal replacement therapy with Slow Low Efficient Dialysis (SLED) will be considered. For sepsis-induced hypotension, noradrenaline is the preferred vasopressor, with terlipressin as a secondary option.  Coagulopathy will be corrected by blood products empirically or based on thromboelastography (TEG, if available) only in the presence of coagulopathy-related bleeding or before any invasive procedure. The dietary need will be assessed daily, and preferred feeding was enteral with or without nutritional supplements, and parenteral nutrition will be used in case of feed intolerance. Etiology-specific treatments will be administered, such as corticosteroids for severe alcoholic hepatitis and tenofovir for HBV reactivation. When indicated and feasible, bridging therapies like liver dialysis (Prometheus/MARS) or plasmapheresis will be employed. Liver transplantation will be advised for patients meeting criteria, including a AARC score >10, MELD score of 30 or higher, CLIF ACLF Grade-II/III, any grade of hepatic encephalopathy, two or more organ failures, steroid nonresponse in cases of severe alcoholic hepatitis or autoimmune flare, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), or refractory variceal bleeding. Supportive or bridging therapies will be provided until transplantation, recovery, 1 year follow-up, or death.

Follow up Protocol

During Hospital stay- D1, 2, 3, Day 7

OPD Follow up-D15, D30, D60, D90 and monthly till 1 year.

Monitoring

Clinical**- Disease severity, laboratory, imaging USG, Clinical (complication, OF, Therapy, LT and any Liver Related Events (LREs). LSM,**

Basic science samples at D1/2/3, D7, D30, D90, D180 for immunologic, proteomic, EVs, regenerative signatures for infection, new OF, survival without LT and reversal/regression /recompensation

***AI lab-***Parameters above both at baseline and different time points as above for AI models for infection, new OF, survival without LT and reversal/regression /recompensation or complication.