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Brief Summary
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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. |