Acetaminophen Acute Liver Failure Research Articles

Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study.

The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy. Propensity score-matched retrospective cohort analysis. Tertiary North American liver transplant centers. Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry. Molecular adsorbent recirculating system treatment versus standard medical therapy (control). One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all). Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.

2351 NAC of All Trades: Use of N-acetylcysteine in Cocaine-Induced Acute Liver Failure

INTRODUCTION: Among patients with acute liver failure (ALF), drug-induced liver injury (DILI) presents a challenging clinical syndrome with limited therapeutic options. N-acetylcysteine (NAC) is a mainstay of treatment in acetaminophen-induced ALF, acting as an antioxidant, a vasodilator and a glutathione precursor. However, it has been used with success in other toxic ingestions causing ALF, and its beneficial effects do not seem to be unique to acetaminophen-induced hepatotoxicity. We present a case of ALF after acute cocaine ingestion with rapid recovery after administration of IV NAC. CASE DESCRIPTION/METHODS: A 58 year-old-male with a past medical history of chronic hepatitis C without cirrhosis and polysubstance abuse presented with acute psychosis. On arrival he was tachycardic but hemodynamically stable, with psychomotor agitation and fear delusions. He endorsed recent heavy cocaine ingestion. Initial labs demonstrated acute kidney injury, rhabdomyolysis and mild transaminitis; AST 59, ALT 56. Toxicology workup was positive for cocaine with undetectable acetaminophen, ethanol and salicylate levels. The following day however, he developed fulminant hepatic failure, AST >7000, ALT 2,568 (Figure 1) with progressive coagulopathy, INR 2.14, albumin 2.9, platelets 120. Of note, despite chronic hepatitis C, there was no evidence of cirrhosis and preserved liver synthetic function at presentation, INR 1.10, albumin 4.7, platelets 254. Our patient was not a candidate for liver transplant (LT), and decision was made to initiate IV NAC therapy, 140 mg/kg bolus followed by 70 mg/kg daily. Transaminases rapidly normalized after only 3 days of therapy, and he was discharged in stable condition. DISCUSSION: ALF is a rare but challenging syndrome, for which LT is the only curative treatment available. NAC is well established as an antidote in acetaminophen ALF, yet its mechanisms are applicable to other forms of DILI as well. Cocaine hepatotoxicity has been reported in humans, and is well studied in animal models. Studies in mice suggest toxic metabolites play a critical role, much like acetaminophen ALF. These species deplete glutathione, decrease hepatic blood flow, generate reactive oxygen species and cause lipid peroxidation of membranes. We present a case of ALF secondary to cocaine ingestion in the setting of underlying chronic hepatitis C, with rapid recovery after fluid resuscitation and IV NAC. NAC therapy has minimal adverse effects, and may be lifesaving in patients with ALF who are not candidates for LT.

Outcomes and Complications of Intracranial Pressure Monitoring in Acute Liver Failure

To determine if intracranial pressure monitor placement in patients with acute liver failure is associated with significant clinical outcomes. Retrospective multicenter cohort study. Academic liver transplant centers comprising the U.S. Acute Liver Failure Study Group. Adult critically ill patients with acute liver failure presenting with grade III/IV hepatic encephalopathy (n = 629) prospectively enrolled between March 2004 and August 2011. Intracranial pressure monitored (n = 140) versus nonmonitored controls (n = 489). Intracranial pressure monitored patients were younger than controls (35 vs 43 yr, p < 0.001) and more likely to be on renal replacement therapy (52% vs 38%, p = 0.003). Of 87 intracranial pressure monitored patients with detailed information, 44 (51%) had evidence of intracranial hypertension (intracranial pressure > 25 mm Hg) and overall 21-day mortality was higher in patients with intracranial hypertension (43% vs 23%, p = 0.05). During the first 7 days, intracranial pressure monitored patients received more intracranial hypertension-directed therapies (mannitol, 56% vs 21%; hypertonic saline, 14% vs 7%; hypothermia, 24% vs 10%; p < 0.03 for each). Forty-one percent of intracranial pressure monitored patients received liver transplant (vs 18% controls; p < 0.001). Overall 21-day mortality was similar (intracranial pressure monitored 33% vs controls 38%, p = 0.24). Where data were available, hemorrhagic complications were rare in intracranial pressure monitored patients (4 of 56 [7%]; three died). When stratifying by acetaminophen status and adjusting for confounders, intracranial pressure monitor placement did not impact 21-day mortality in acetaminophen patients (p = 0.89). However, intracranial pressure monitor was associated with increased 21-day mortality in nonacetaminophen patients (odds ratio, ~ 3.04; p = 0.014). In intracranial pressure monitored patients with acute liver failure, intracranial hypertension is commonly observed. The use of intracranial pressure monitor in acetaminophen acute liver failure did not confer a significant 21-day mortality benefit, whereas in nonacetaminophen acute liver failure, it may be associated with worse outcomes. Hemorrhagic complications from intracranial pressure monitor placement were uncommon and cannot account for mortality trends. Although our results cannot conclusively confirm or refute the utility of intracranial pressure monitoring in patients with acute liver failure, patient selection and ancillary assessments of cerebral blood flow likely have a significant role. Prospective studies would be required to conclusively account for confounding by illness severity and transplant.

Prevalence of acute kidney injury network (AKIN) in pediatric non acetaminophen acute liver failure (pNA-ALF) & addition of akin staging to king's college criteria (Kcc) in pNA-ALF improves prognostic value

A cu te Li ve r Fa ilu re from malnutrition, a host factor known to cause reduced immunocompetence leading to greater risk of multiple viral infections. Aims: To evaluate the role of maternal nutritional factors in acute viral hepatitis (AVH) and acute liver failure (ALF) patients with HEV infection during pregnancy. Methods: The study included 180 pregnant cases of which 72 HEV infected pregnant cases, 78 Non-HEV pregnant cases and 30 control cases were recruited in the study during February 2011 to December 2012. Serological evaluation of virological markers like IgM anti-HAV, HBsAg, anti-HCV Ab and IgM anti-HEV was done by ELISA. Nutritional factors were evaluated by measuring the anthropometric parameters such as body mass index (BMI), height, weight, triceps skin fold thickness, mid arm circumference (MAC), arm span using appropriate readings. Results: The meanmaternal age, gestational age at delivery and hemoglobin levels of HEV infected pregnant patients were 24.32+4.25years, 33.41+3.94weeks and 10.4+1.87 g/ dl respectively. BMI, mid arm circumference and tricep skin fold thickness were found to be significantly lower in ALF pregnant patients compared to their AVH counterparts in the HEV group (P<0.01). Tricep skin fold thickness was found to be significantly lower in ALF pregnant patients in the HEV group compared to AVH pregnant patients in the Non-HEV group (P =0.006). Significant decrease in levels of BMI, MAC and tricep skin fold thickness were observed in AVH pregnant patients with HEV as compared to the pregnant control cases respectively (P<0.01). Conclusion: Statistically significant decrease in levels of BMI, mid arm circumference and tricep skin fold thickness in HEV pregnant women with ALF as compared to the healthy pregnant cases reflects that low nutritional status might contribute towards severity of the disease during pregnancy.