Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. METHODS: A multicentre retrospective study across four major tertiary care centres. RESULTS: As many as 183 ALF patients (median age, 23 years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen per cent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. CONCLUSIONS: Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

A randomized, controlled, prehabilitation intervention to maximize early recovery (PRIMER) in liver transplantation.

Frailty and impaired functional status are associated with adverse outcomes on the liver transplant (LT) waitlist and after transplantation. Prehabilitation prior to LT has rarely been tested. We conducted a 2-arm patient-randomized pilot trial to evaluate the feasibility and efficacy of a 14-week behavioral intervention to promote physical activity prior to LT. Thirty patients were randomized 2:1 to intervention (n = 20) versus control (n = 10). The intervention arm received financial incentives and text-based reminders linked to wearable fitness trackers. Daily step goals were increased by 15% in 2-week intervals. Weekly check-ins with study staff assessed barriers to physical activity. The primary outcomes were feasibility and acceptability. Secondary outcomes included mean end-of-study step counts, short physical performance battery, grip strength, and body composition by phase angle. We fit regression models for secondary outcomes with the arm as the exposure adjusting for baseline performance. The mean age was 61, 47% were female, and the median Model for End-stage Liver Disease sodium (MELD-Na) was 13. One-third were frail or prefrail by the liver frailty index, 40% had impaired mobility by short physical performance battery, nearly 40% had sarcopenia by bioimpedance phase angle, 23% had prior falls, and 53% had diabetes. Study retention was 27/30 (90%; 2 unenrolled from intervention, 1 lost to follow-up in control arm). Self-reported adherence to exercise during weekly check-ins was about 50%; the most common barriers were fatigue, weather, and liver-related symptoms. End-of-study step counts were nearly 1000 steps higher for intervention versus control: adjusted difference 997, 95% CI, 147-1847; p = 0.02. On average, the intervention group achieved daily step targets 51% of the time. A home-based intervention with financial incentives and text-based nudges was feasible, highly accepted, and increased daily steps in LT candidates with functional impairment and malnutrition.

The Evolving Profile of Idiosyncratic Drug-Induced Liver Injury.

Idiosyncratic drug-induced liver injury (DILI) is an infrequent but important cause of liver disease. Newly identified causes of DILI include the COVID vaccines, turmeric, green tea extract, and immune checkpoint inhibitors. DILI is largely a clinical diagnosis of exclusion that requires evaluation for more common causes of liver injury and a compatible temporal association with the suspect drug. Recent progress in DILI causality assessment includes the development of the semi-automated revised electronic causality assessment method (RECAM) instrument. In addition, several drug-specific HLA associations have been identified that can help with the confirmation or exclusion of DILI in individual patients. Various prognostic models can help identify the 5%-10% of patients at highest risk of death. Following suspect drug cessation, 80% of patients with DILI fully recover, whereas 10%-15% have persistently abnormal laboratory studies at 6 months of follow-up. Hospitalized patients with DILI with an elevated international normalized ratio or mental status changes should be considered for N-acetylcysteine therapy and urgent liver transplant evaluation. Selected patients with moderate to severe drug reaction with eosinophilia and systemic symptoms or autoimmune features on liver biopsy may benefit from short-term corticosteroids. However, prospective studies are needed to determine the optimal patients and dose and duration of steroids to use. LiverTox is a comprehensive, freely accessible Web site with important information regarding the hepatotoxicity profile of more than 1000 approved medications and 60 herbal and dietary supplement products. It is hoped that ongoing "omics" studies will lead to additional insight into DILI pathogenesis, improved diagnostic and prognostic biomarkers, and mechanism-based treatments.

Herb-induced Liver Injury-A Guide to Approach. Lessons from the Tinospora cordifolia (Giloy) Case Series Story.

Background: Tinospora cordifolia (TC) is being increasingly consumed in India for its health and suggested immune-enhancing benefits in preventing and countering COVID-19. We previously published our experience of hepatotoxicity with self-medication of TC in six individuals. Since herb-induced liver injury (HILI) has been described with Tinospora crispa (TCR) consumption, it was contested that our patients may have mistakenly self-medicated with TCR which is similar in appearance to TC. Methods: We collected the four plant samples and two commercial preparations that were consumed by our patients for further analysis. The six samples underwent high performance thin layer chromatography phytochemical analysis and DNA barcoding studies for the confirmation of the genus and species. The four plant part samples which included stems and leaves were also analysed by a botanist for the characteristic morphological and microscopic features. Results: Based on morphological, microscopic, phytochemical and DNA studies, the four plant part samples were identified as TC. The two commercial preparations could not be analysed on phytochemical analysis or DNA barcoding studies due to other ingredients that most likely interfered with the analysis. The herb consumed by our study subjects was confirmed to be Tinospora cordifolia. Conclusion: We have highlighted the key morphological and phytochemical differences between these two species. We propose an algorithmic approach to accurately identify the implicated herb in cases of HILI. Future studies on causality need to focus on the serological/histopathological identification of active herb/metabolites in human tissues.

Early Diagnosis and Prevention of Infections in Cirrhosis.

Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective ß-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of ß-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.

Strategy and Efficacy of Generic and Pan-genotypic Sofosbuvir/Velpatasvir in Chronic Hepatitis C Virus: A Myanmar Experience.

BACKGROUND: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays. AIM: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure. METHODS: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested. RESULTS: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested. CONCLUSIONS: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

Viral eradication is required for sustained improvement of patient-reported outcomes in patients with hepatitis C.

BACKGROUND: Clearance of chronic HCV infection improves quality of life and other patient-reported outcomes (PROs). Lack of placebo-controlled data led to concerns about the extent of contribution of viral eradication to PRO improvement. AIM: To assess PRO changes in HCV patients initially randomized to placebo treatment who received SOF/VEL/VOX in a deferred treatment substudy. METHODS: HCV-infected direct-acting antivirals-experienced patients who received placebo treatment in POLARIS-1 subsequently received SOF/VEL/VOX (400/100/100 mg) daily for 12 weeks. PROs were prospectively collected using SF-36v2, CLDQ-HCV, FACIT-F, WPAI:SHP. RESULTS: Of 147 patients treated, most were male (79%), white (82%), 33% had cirrhosis, 99% had HCV genotype 1 with SVR-12 of 97%. During treatment with placebo, there were no significant changes in any PROs from patients' own baseline (all P > .05) except for the Worry domain of CLDQ-HCV. However, soon after initiation of treatment with SOF/VEL/VOX, significant PRO improvements were noted: +2.4% to +8.1% of a PRO range size, P < .05 for 6 of the 26 studied PROs, by treatment week 4; +2.0% to +8.3%, P < .05 for 14/26 PROs by treatment week 12. Achieving SVR was associated with similar or greater PRO improvement: +2.5% to +11.9%, P < .05 for 24/26 PROs, by SVR-12; +3.2% to +14.9%, P < .05 for 23/26 PROs, by SVR-24. In multivariate regression analysis, being viraemic was associated with PRO impairment: beta from -2.4% to -8.5%, P < .05 for all but one PRO. CONCLUSION: Treatment with SOF/VEL/VOX for 12 weeks led to significant and sustainable improvement in patient-reported outcomes in patients who had previously failed another direct-acting antiviral regimen.

The Impact of Albumin Use on Resolution of Hyponatremia in Hospitalized Patients With Cirrhosis.

OBJECTIVES: Hyponatremia is associated with poor outcomes in cirrhosis independent of MELD. While intravenous albumin has been used in small series, its role in hyponatremia is unclear. The aim of this study is to determine the effect of albumin therapy on hyponatremia. METHODS: Hospitalized cirrhotic patients included in the NACSELD (North American Consortium for End-Stage Liver Disease) cohort with hyponatremia (Na <130mmol/L) were divided into those receiving intravenous albumin or not. Determinants of hyponatremia resolution (Na ≥135 meq/L) and 30-day survival were analyzed using regression and ANCOVA models. RESULTS: Overall, 2435 patients, of whom 1126 had admission hyponatremia, were included. Of these, 777 received 225 (IQR 100,400) g of albumin, while 349 did not. Patients given albumin had a higher admission MELD score, and serum creatinine and lower admission Na and mean arterial pressure (MAP). However they experienced a higher maximum Na and hyponatremia resolution (69% vs 61%, p = 0.008) compared to those who did not. On regression, delta Na was independently associated with admission creatinine, MAP and albumin use. On ANCOVA with logistic regression, there was a significant difference in hyponatremia resolution between those who did or did not receive albumin, even after adjustment for admission Na and GFR (85.41% vs 44.78%, p = 0.0057, OR: 1.50 95% CI: 1.13-2.00). Independent predictors of 30-day survival were hyponatremia resolution, age, ACLF, and admission GFR. CONCLUSION: Hospitalized patients with cirrhosis and hyponatremia who received intravenous albumin had a higher rate of hyponatremia resolution independent of renal function and baseline sodium levels, which was in turn associated with a better 30-day survival.

Prediction of Fungal Infection Development and Their Impact on Survival Using the NACSELD Cohort.

OBJECTIVES: Bacterial infections are associated with negative outcomes in cirrhosis but fungal infections are being increasingly recognized. The objective of this study is to define risk factors for fungal infection development and impact on 30-day survival. METHODS: In a large, multi-center cirrhotic inpatient cohort, demographics, cirrhosis details, intensive care unit (ICU), organ failures/acute-on-chronic liver failure (ACLF), and 30-day survival were compared between patients without infections and with bacterial infections alone, with those with fungal infections. Variables associated with fungal infection development were determined using multi-variable regression. Ordinal variables (0=no infection, 1=community-acquired bacterial infection, 2=nosocomial bacterial, and 3=fungal infection) were input into a 30-day survival model. RESULTS: A total of 2,743 patients (1,691 no infection, 918 bacterial, and 134 fungal infections) were included. Patients with fungal infection, all of which were nosocomial, were more likely to be admitted with bacterial infections, on spontaneous bacterial peritonitis prophylaxis, and have diabetes and advanced cirrhosis. Bacterial infection types did not predict risk for fungal infections. Multi-variable analysis showed male gender to be protective, whereas diabetes, longer stay, ICU admission, acute kidney injury (AKI), and admission bacterial infection were associated with fungal infection development (area under the curve (AUC)=0.82). Fungal infections were associated with significantly higher ACLF, inpatient stay, ICU admission, and worse 30-day survival. The case fatality rate was 30% with most fungal infections but >50% for fungemia and fungal peritonitis. On a multi-variable analysis, age, AKI, model for end-stage liver disease, ICU admission, and ordinal infection variables impaired survival (P<0.0001, AUC=0.83). CONCLUSIONS: Fungal infections are associated with a poor 30-day survival in hospitalized cirrhotic patients compared with uninfected patients, and those with bacterial infections. Patients with diabetes, AKI, and those with an admission bacterial infection form a high-risk subgroup.

Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group.

BACKGROUND & AIMS: In the United States, nearly 1000 annual cases of heat stroke are reported but the frequency and outcome of severe liver injury in such patients is not well described. The aim of this study was to describe cases of acute liver injury (ALI) or failure (ALF) caused by heat stroke in a large ALF registry. METHODS: Amongst 2675 consecutive subjects enrolled in a prospective observational cohort of patients with ALI or ALF between January 1998 and April 2015, there were eight subjects with heat stroke. RESULTS: Five patients had ALF and three had ALI. Seven patients developed acute kidney injury, all eight had lactic acidosis and rhabdomyolysis. Six patients underwent cooling treatments, three received N-acetyl cysteine (NAC), three required mechanical ventilation, three required renal replacement therapy, two received vasopressors, one underwent liver transplantation, and two patients died-both within 48 hours of presentation. All cases occurred between May and August, mainly in healthy young men because of excessive exertion. CONCLUSIONS: Management of ALI and ALF secondary to heat stroke should focus on cooling protocols and supportive care, with consideration of liver transplantation in refractory patients.

Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study.

OBJECTIVE: Due to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants. DESIGN: HCV-TARGET, an international, prospective observational study evaluates clinical practice data on novel antiviral therapies at 44 academic and 17 community medical centres in North America and Europe. Clinical data were centrally abstracted from medical records. Selection of treatment regimen and duration was the investigator's choice. The primary efficacy outcome was sustained virological response 12 weeks after therapy (SVR12). RESULTS: Between December 2013 and April 2015, 321 patients completed 12 weeks (n=283) or 16 weeks (n=38) of treatment with SOF and RBV. Prior treatment experience and cirrhosis was more frequent among patients in the 16-week regimen compared with 12 weeks (52.6% vs 27.6% and 63.2% vs 21.9%, respectively). Overall, SVR12 was 88.2%. The SVR12 in patients without cirrhosis was 91.0% and 92.9% for 12 or 16 weeks of therapy, respectively. In patients with cirrhosis treated for 12 or 16 weeks, SVR12 was 79.0% and 83%. In the multivariate analysis, liver cirrhosis, lower serum albumin and RBV dose at baseline were significantly associated with SVR12. Common adverse events (AEs) included fatigue, anaemia, nausea, headache, insomnia, rash and flu-like symptoms. Discontinuation due to AEs occurred in 2.8%. CONCLUSIONS: In this clinical practice setting, SOF and RBV was safe and effective for treatment of patients with HCV GT2 infection. TRIAL REGISTRATION NUMBER: NCT01474811.

Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study.

This prospective, randomized, phase 2 study in subjects with recurrent hepatitis C virus (HCV) genotype 1 postorthotopic liver transplant evaluated once-daily simeprevir 150 mg + sofosbuvir 400 mg, with and without ribavirin 1000 mg. Primary endpoint was proportion of subjects with week 12 sustained virologic response (SVR12). Thirty-three subjects without cirrhosis were randomized 1:1:1 into three arms (stratified by genotype/subtype and Q80K): Arm 1, simeprevir + sofosbuvir + ribavirin, 12 weeks; Arm 2, simeprevir + sofosbuvir, 12 weeks; Arm 3, simeprevir + sofosbuvir, 24 weeks; 13 additional subjects (two with cirrhosis, 11 without cirrhosis) entered Arm 3. All 46 subjects received at least one dose of study drug; median age, 60 years; 73.9% male; 80.4% White; 71.7% genotype/subtype 1a [12 (36.4%) of these had Q80K]; median 4.5 years post-transplant. Among randomized subjects, SVR12 was achieved by 81.8% in Arm 1, 100% in Arm 2, and 93.9% in Arm 3; two subjects did not achieve SVR12: one viral relapse (follow-up week 4; Arm 1) and one missing follow-up week 12 data. In total, five subjects had a serious adverse event, considered unrelated to treatment per investigator. Simeprevir exposure was increased relative to the nontransplant setting, but not considered clinically relevant. Simeprevir + sofosbuvir treatment, with or without ribavirin, was efficacious and well tolerated (ClinicalTrials.gov Identifier: NCT02165189).

Spirituality, Religiosity, and Health: a Comparison of Physicians' Attitudes in Brazil, India, and Indonesia.

BACKGROUND: One of the biggest challenges in the spirituality, religiosity, and health field is to understand how patients and physicians from different cultures deal with spiritual and religious issues in clinical practice. PURPOSE: The present study aims to compare physicians' perspectives on the influence of spirituality and religion (S/R) on health between Brazil, India, and Indonesia. METHOD: This is a cross-sectional, cross-cultural, multi-center study carried out from 2010 to 2012, examining physicians' attitudes from two continents. Participants completed a self-rated questionnaire that collected information on sociodemographic characteristics, S/R involvement, and perspectives concerning religion, spirituality, and health. Differences between physicians' responses in each country were examined using chi-squared, ANOVA, and MANCOVA. RESULTS: A total of 611 physicians (194 from Brazil, 295 from India, and 122 from Indonesia) completed the survey. Indonesian physicians were more religious and more likely to address S/R when caring for patients. Brazilian physicians were more likely to believe that S/R influenced patients' health. Brazilian and Indonesians were as likely as to believe that it is appropriate to talk and discuss S/R with patients, and more likely than Indians. No differences were found concerning attitudes toward spiritual issues. CONCLUSION: Physicians from these different three countries had very different attitudes on spirituality, religiosity, and health. Ethnicity and culture can have an important influence on how spirituality is approached in medical practice. S/R curricula that train physicians how to address spirituality in clinical practice must take these differences into account.

Prevalence and risk factors for patient-reported joint pain among patients with HIV/hepatitis C coinfection, hepatitis C monoinfection, and HIV monoinfection.

BACKGROUND: To determine the prevalence of patient-reported joint pain among patients with human immunodeficiency virus (HIV)/chronic hepatitis C virus (HCV) coinfection, chronic HCV monoinfection, and HIV monoinfection followed in hepatology and infectious disease outpatient practices. METHODS: Standardized interviews were performed among 79 HIV/HCV-coinfected, 93 HCV-monoinfected, and 30 HIV-monoinfected patients in a cross-sectional study within hepatology and infectious disease clinics at three centers. The Multi-Dimensional Health Assessment Questionnaire was used to ascertain joint pain and associated symptoms. Information on potential risk factors for joint pain was obtained during the interview and by chart review. Logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of joint pain associated with risk factors of interest among chronic HCV-infected and HIV-infected patients. RESULTS: Joint pain was more commonly reported in HCV-monoinfected than HIV/HCV-coinfected (71% versus 56%; p = 0.038) and HIV-monoinfected (71% versus 50%; p = 0.035) patients. A previous diagnosis of arthritis and current smoking were risk factors for joint pain among HCV-infected patients (arthritis: aOR, 4.25; 95% CI, 1.84-9.81; smoking: aOR, 5.02; 95% CI, 2.15-11.74) and HIV-infected (arthritis: aOR, 5.36; 95% CI, 2.01-14.25; smoking: aOR, 6.07; 95% CI, 2.30-16.00) patients. CONCLUSION: Patient-reported joint pain was prevalent among all three groups, but more common among chronic HCV-monoinfected than either HIV/HCV-coinfected or HIV-monoinfected patients. A prior diagnosis of arthritis and current smoking were risk factors for patient-reported joint pain among both HCV-infected and HIV-infected patients.

Validity of diagnostic codes and laboratory tests of liver dysfunction to identify acute liver failure events.

PURPOSE: Identification of acute liver failure (ALF) is important for post-marketing surveillance of medications, but the validity of using ICD-9 diagnoses and laboratory data to identify these events within electronic health records is unknown. We examined positive predictive values (PPVs) of hospital ICD-9 diagnoses and laboratory tests of liver dysfunction for identifying ALF within a large, community-based integrated care organization. METHODS: We identified Kaiser Permanente Northern California health plan members (2004-2010) with a hospital diagnosis suggesting ALF (ICD-9 570, 572.2, 572.4, 572.8, 573.3, 573.8, or V42.7) plus an inpatient international normalized ratio ≥1.5 (off warfarin) and total bilirubin ≥5.0 mg/dL. Hospital records were reviewed by hepatologists to adjudicate ALF events. PPVs for confirmed outcomes were determined for individual ICD-9 diagnoses, diagnoses plus prescriptions for hepatic encephalopathy treatment, and combinations of diagnoses in the setting of coagulopathy and hyperbilirubinemia. RESULTS: Among 669 members with no pre-existing liver disease, chart review confirmed ALF in 62 (9%). Despite the presence of co-existing coagulopathy and hyperbilirubinemia, individual ICD-9 diagnoses had low PPVs (range, 5-15%); requiring prescriptions for encephalopathy treatment did not increase PPVs of these diagnoses (range, 2-23%). Hospital diagnoses of other liver disorders (ICD-9 573.8) plus hepatic coma (ICD-9 572.2) had high PPV (67%; 95%CI, 9-99%) but only identified two (3%) ALF events. CONCLUSIONS: Algorithms comprising relevant hospital diagnoses, laboratory evidence of liver dysfunction, and prescriptions for hepatic encephalopathy treatment had low PPVs for confirmed ALF events. Studies of ALF will need to rely on medical records to confirm this outcome.

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.