Autoimmune hepatitis presenting as acute liver failure: A 20-year retrospective review of North America.

Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival. This study included adults hospitalized with acute liver failure enrolled in the Acute Liver Failure Study Group Registry between 1998 and 2019 from 32 centers within the US. The etiology of all cases was reviewed by the Adjudication Committee, and all cases identified as autoimmune hepatitis were included. Acute liver injury was defined as an INR ≥2.0 without encephalopathy and acute liver failure as INR ≥ 1.5 with encephalopathy. Laboratory and clinical data were reviewed. Variables significantly associated with 21-day transplant-free survival were used to develop a multivariable logistic regression model.  A total of 193 cases of acute liver failure secondary to autoimmune hepatitis were identified and reviewed. There were 161 patients (83.4%) diagnosed with acute liver failure on enrollment, and 32 (16.6%) developed acute liver failure during hospitalization. At 21 days, 115 (59.6%) underwent liver transplantation, 28 (14.5%) had transplant-free survival, and 46 (23.8%) died before liver transplantation. Higher admission values of bilirubin, INR, and coma grade were associated with worse outcomes. A prognostic index incorporating bilirubin, INR, coma grade, and platelet count had a concordance statistic of 0.84. Acute liver failure secondary to autoimmune hepatitis is associated with a high short-term mortality. We developed a model specifically for autoimmune hepatitis that may be helpful in predicting 21-day transplant-free survival and early identification of patients in need of expedited liver transplant evaluation.

Indwelling Tunneled Pleural Catheters for Refractory Hepatic Hydrothorax in Patients With Cirrhosis: A Multicenter Study.

BACKGROUND: The outcome of indwelling pleural catheter (IPC) use in hepatic hydrothorax (HH) is unclear. This study aimed to review the safety and feasibility of the IPC in patients with refractory HH. METHODS: A retrospective multicenter study of patients with HH from January 2010 to December 2016 was performed. Inclusion criteria were refractory HH treated with an IPC and an underlying diagnosis of cirrhosis. Records were reviewed for patient demographics, operative reports, and laboratory values. The Kaplan-Meier method was used to estimate catheter time to removal. The Cox proportional hazard model was used to evaluate for independent predictors of pleurodesis and death. RESULTS: Seventy-nine patients were identified from eight institutions. Indication for IPC placement was palliation in 58 patients (73%) and bridge to transplant in 21 patients (27%). The median in situ dwell time of all catheters was 156 days (range, 16-1,978 days). Eight patients (10%) were found to have pleural space infection, five of whom also had catheter-site cellulitis. Two patients (2.5%) died secondary to catheter-related sepsis. Catheter removal secondary to spontaneous pleurodesis was achieved in 22 patients (28%). Median time from catheter insertion to pleurodesis was 55 days (range, 10-370 days). Older age was an independent predictor of mortality on multivariate analysis (hazard ratio, 1.05; P = .01). CONCLUSIONS: We present, to our knowledge, the first multicenter study examining outcomes related to IPC use in HH. Ten percent infection risk and 2.5% mortality were identified. IPC placement may be a reasonable clinical option for patients with refractory HH, but it is associated with significant adverse events in this morbid population.

Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis.

OBJECTIVES: Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. METHODS: Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention. RESULTS: Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline. CONCLUSIONS: PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Two-year outcomes in initial survivors with acute liver failure: results from a prospective, multicentre study.

BACKGROUND & AIMS: The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. The aim of this study was to provide an overview of the 2-year clinical outcomes among initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrolment in the Acute Liver Failure Study Group (ALFSG). METHODS: Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. RESULTS: Two-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non-APAP SS (75.5%) (P < 0.0001). The causes of death were similar in the three groups but the time to death was significantly longer in the LT recipients (P < 0.0001). Independent predictors of 2-year mortality in the APAP group were a high serum phosphate level and patient age (c-statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non-APAP group (c-statistic = 0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c-statistic = 0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (P < 0.05). CONCLUSIONS: Two-year outcomes in initial survivors of ALF are generally good but non-APAP patients have a significantly lower survival which may relate to pre-existing medical comorbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow-up from ongoing psychiatric and substance abuse issues.

Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C.

BACKGROUND: Excessive alcohol consumption is associated with an increased risk for fibrosis progression and cirrhosis in patients with chronic hepatitis C virus (HCV) infection. However, the impact of mild-moderate alcohol use on the severity of liver fibrosis is unclear. GOALS: The objective of this retrospective study was to assess the impact of mild alcohol consumption on liver fibrosis in patients with chronic HCV. STUDY: 857 patients with well-characterized chronic HCV were enrolled. All underwent liver biopsy to assess hepatic fibrosis. The duration of HCV infection was determined by detailed questionnaires and personal interviews. Alcohol use history was estimated by the Skinner Alcohol Examination Questionnaire. Mild alcohol use was defined as 1 to 3 alcoholic beverages/day (<30 grams/d). Participants were divided into 4 groups based on their average lifetime daily alcohol consumption (essentially none, <1, 1 to 3 or >3 drinks/d) and into quartiles based on their presumed duration of HCV infection (<23, 23 to 31, 31 to 38, or >38 y). RESULTS: Mean alcohol consumption was 2.7 drinks/d; mean duration of HCV infection was 29 years. Daily alcohol consumption was not significantly higher among participants with advanced fibrosis (bridging fibrosis or cirrhosis) when compared with those with none or portal fibrosis (3.2 vs. 2.2 drinks/d, respectively, P=NS). The degree of fibrosis increased significantly with the duration of HCV infection (P<0.0001) and was independent of mild-moderate alcohol consumption. CONCLUSIONS: Mild alcohol use does not seem to adversely affect the severity of fibrosis in patients with chronic HCV.

Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy.

Monitoring of intracranial pressure (ICP) in acute liver failure (ALF) is controversial as a result of the reported complication risk (approximately 20%) and limited therapeutic options for intracranial hypertension. Using prospectively collected information from 332 patients with ALF and severe encephalopathy, we evaluated a recent experience with ICP monitoring in the 24 centers constituting the U.S. ALF Study Group. Special attention was given to the rate of complications, changes in management, and outcome after liver transplantation (LT). ICP monitoring was used in 92 patients (28% of the cohort), but the frequency of monitoring differed between centers (P < 0.001). ICP monitoring was strongly associated with the indication of LT (P < 0.001). A survey performed in a subset of 58 patients with ICP monitoring revealed intracranial hemorrhage in 10.3% of the cohort, half of the complications being incidental radiological findings. However, intracranial bleeding could have contributed to the demise of 2 patients. In subjects listed for LT, ICP monitoring was associated with a higher proportion of subjects receiving vasopressors and ICP-related medications. The 30-day survival post-LT was similar in both monitored and nonmonitored groups (85% vs. 85%). In conclusion, the risk of intracranial hemorrhage following ICP monitoring may have decreased in the last decade, but major complications are still present. In the absence of ICP monitoring, however, patients listed for LT appear to be treated less aggressively for intracranial hypertension. In view of the high 30-day survival rate after LT, future studies of the impact of intracranial hypertension should also focus on long-term neurological recovery from ALF.