Acute fatty liver -a case presentation and management

Acute fatty liver -a case presentation and management

1. A CASE OF acute liver failure in the intensive care unit . Dept of critical care medicine – Abhishek jha 29 th august, 2024.

2. DEMOGRAPHICS & HISTORY OF PRESENTING ILLNESS 12/M Master Ansh Shende, r/o Mumbai, was transferred to us from a nearby hospital with a history of Fever x 3 days before admission, resolved on taking oral OTC medicines, Vomiting – multiple episodes for 2-3 days at home, containing normal food particles, no blood in vomitus, Altered sensorium x 1 day, for which he was taken to a nearby hospital and admitted to the Intensive Care Unit and evaluated.

3. COURSE OF ILLNESS After working him up at the hospital outside, he was found to have severely deranged liver enzymes, deranged coagulation profile and was hence shifted to Fortis hospital Mulund, for further management of Acute liver Failure with unidentified etiology and possibility of requirement of a liver Transplant. On arrival to our ED, the transplant team was informed as well and the patient was admitted to the Surgical ICU.

4. PHYSICAL EXAMINATION AND VITALS O/E – Drowsy, Lethargic Temperature – 98.9 degrees Fahrenheit HR – 124/min BP – 133/70 mmHg RR – 23 cycles/min SPO2 – 96% on Room Air. HGT – 97mg/dL

5. SYSTEMIC EXAMINATION CNS – drowsy, disoriented. Not following commands, hence rest of the higher mental functions couldn’t be assessed. Moving all 4 limbs spontaneously, B/L pupils 3mm ERTL. RS – Air entry B/L equal, no added breath sounds. CVS – S1, S2 + No gallop/ murmurs. P/A- soft, Non tender. No Significant medical history in the past No travel history / No ayurvedic or herbal medication / No h/o outside food consumption.

6. KEY LAB INVESTIGATIONS – 1 ST 6 HOURS T. BILI – 7.42 (DIRECT 6.4) SGOT – 4164 SGPT – 4484 PT/INR – 57/ 5.0 ARTERIAL AMMONIA - 200 ABG – METABOLIC + LACTIC ACIDOSIS with Lactates ~ 4 HAV IgM +; HSV 1 & 2 : REACTIVE

7. MANAGEMENT – DAY 1 He was electively intubated and ventilated on Day 1 for airway protection, after thorough discussion with relatives and obtaining proper consents. Central line and Arterial lines were inserted for continuous monitoring + infusions and sedation/paralysis. 3% NS infusion was started with a target Na of 145-150 to counter cerebral edema and avoid worsening, with 8 hourly Sodium levels. A decision to initiate therapeutic Plasma Exchange was taken, after discussing all pros and cons of the treatment options with the family due to the severity of the illness and the high mortality rate of ALF. Full volume PLEX was done with 1 plasma volume using FFP and crystalloids.

8. MANAGEMENT – day 1 He was Started on broad spectrum antibiotics – IV Piperacillin Tazobactam 4.5gm 8 hourly, IV Acyclovir 500mg 8 hourly and anti hepatic encephalopathy measures with Rifaximin, Lactulose syrup and enemas to ensure bowel movement at least 3-4 times/day, with 8 hourly monitoring of arterial Ammonia. Mechanically ventilated with a high RR to washout CO2 with target pCO2 levels of 30-35mmHg, as part of ICP reduction measures. N Acetyl cysteine infusion was started at the standard weight-based regimen. Dextrose 25% Infusion was started for recurring hypoglycemia with 2 nd hourly HGT monitoring.

9. Management – day 2 After seeing an adequate response to PLEX on the first day, with reduction in the levels of Arterial ammonia as well as the INR from 5  2.68, he was initiated on a 2 nd cycle of Plasmapheresis on the 13 th August, day 2 in the Intensive Care Unit. A NCCT brain was done on the 2 nd day to look for any s/o worsening cerebral edema and herniation, due to severely high systolic pressures and relative bradycardia, with HR ranging from 56-64 and SBP ~ 170-180mmHg despite adequate sedation and analgesia with Fentanyl, Propofol, Midazolam and Atracurium infusions – which showed no such herniation. We had then switched to Thiopentone infusion and stopped Midazolam / propofol due to the high risk of developing Propofol infusion syndrome and an inadequate response.

10. DAYS 3-6 Subsequently, the patient’s lab parameters improved with Ammonia ranging between 40-80 and a gradual correction in his INR levels to less than 2.5 Neurologically, the patient started to improve and was following vocal commands upon stopping sedation, after which he was successfully extubated. The Liver enzymes had a significant reduction as well from > 4000 to 150 ~ 300. All lines were removed and infusions stopped by the 4th day. He was discharged directly from the ICU on day 6 and is expected to follow up with us after 14 days.

11. INVESTIGATIONS 12/08 /2 4 13/08/24 14 / 08 /2 4 1 5 / 08 /2 4 1 6 / 08 /2 4 HB 10.9 10.6 9.1 8.7 8.8 TLC 12.67 8.30 8.01 5.66 8.44 PLT 3.39 2.29 1.96 2.09 2.50 Na 135 143 144 145 144 INR 5.0 2.02 1.87 1.98 1.75 SGOT 4164 3776 192 150 178 SGPT 4484 934 299 320 339 CREAT 0.71 0.66 0.53 0.41 0.53 AMMONIA 200 104 60 81 88

12. ROLE OF PLEX IN ALF In PLEX, a patient's plasma is replaced with plasma from a donor, which can help by:  Removing inflammatory cytokines  Replenishing coagulation factors  Removing circulating toxins  Removing DAMPs, PAMPs  Ameliorating the overactive innate immune and inflammatory response  Reversing failure/dysfunction of liver and other vital organs

13. EVIDENCE OF PLEX IN ALF PLEX can be a promising nontransplant option for treating ALF syndromes. It can be performed in any hospital that has renal dialysis and blood bank facilities, as well as a high-dependency unit or intensive care unit to monitor the patient during the procedure.   According to the ASFA guidelines, PLEX is an accepted treatment for ALF. Some studies have found that PLEX can improve survival in patients with ALF, with one study reporting a 78.5% survival rate for patients treated with PLEX compared to 57.3% overall. Other studies have found that PLEX can also have benefits for ACLF patients, including a mortality benefit and decreased bilirubin levels. PLEX may also be used as a bridge to transplant or for patients who are not fit for transplant. 

14. LEARNING POINTS FROM THE CASE Managing a case of acute liver failure in the Intensive Care with prompt intervening measures such as early intubation and sedation along with ICP reduction, Therapeutic Plasma Exchange and CRRT (if required) can help avoid a liver transplant and cause severe reduction in long term morbidity and mortality, associated with it. ICP REDUCTION MEASURES Early intubation and sedation / paralysis Head in Midline with PUP position 30-45 degrees Hyperventilation with target pCO2 30-35mmHg Osmotherapy – Mannitol / 3% NS boluses Sedation – Midazolam / Propofol and SOS Thiopentone

15. Key elements in managing acute liver failure Early intubation and mechanical ventilation as a part of airway protection as well as raised ICP management Judicious fluid management guided by any of the hemodynamic monitoring system CRRT/SLEDD to tackle hyperammonemia which is the major cause of raised ICP Other modalities of treating raised ICP like 3% NS Prophylactic antibiotics to tackle bacteremia Avoidance of blood products to treat coagulopathy unless significant bleeding or a major procedure Role of NAC mainly for PCM induced liver failure but also emergence of evidence in non PCM induced liver failure Plasmapheresis mainly for rat poison induced liver failure but also emerging role in other causes of liver failure LIVER TRANSPLANT

16. Role of NAC in non PCM induced liver failure- meta-analysis of studies showing overall survival

17. Role of NAC in non PCM induced liver failure- meta-analysis of studies showing overall survival -Transplant free survival was also significantly higher in NAC group as compared to non NAC treated group - Non NAC treated patients also stayed longer in hospital

18. What is the evidence in favor of HV-TPE in ALF? Few case studies and case reports Only one single centre RCT- J Hepatol 2016; 64: 69-78

19. Thank you