Background-N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen related acute liver failure.

Until recently, liver transplantation in patients with hepatitis B was associated with a high rate of graft loss and poor survival because of viral recurrence. 1-3 Favorable outcome following liver transplantation for hepatitis B virus (HBV)-related liver disease was made possible with long-term, high-dose, passive immunoprophylaxis using hepatitis B immune globulin (HBIG). 4,5 Hepatitis B still recurs, however, despite HBIG. Recurrence may be caused by saturation of the antibody binding capacity of HBIG by a high viral load, or by mutations in the hepatitis B surface antigen (HBsAg) molecule that render HBIG ineffective. 6,7 Overall recurrence rates with HBIG monotherapy vary from approximately 15% to 50%. 4,5,[8][9][10][11] Using a different dosing schedule, in early experience from our own institution HBV recurrence on HBIG was 44%. 12 The wide disparity in the data reflects differing patient populations, e.g., patients who are HBV-DNA-positive at the time of transplantation have higher rates of recurrence. Moreover, the different dosing regimens of HBIG are also likely to influence recurrence rates. 5,11,13 An alternative approach to preventing HBV recurrence became possible using the purine nucleoside analog reversetranscriptase inhibitor, lamivudine. Demonstration of its efficacy, in the nontransplantation setting, in suppressing HBV-DNA synthesis 14,15 led to studies using lamivudine following liver transplantation as prophylaxis against hepatitis B recurrence, 16,17 or as treatment of de novo or recurrent hepatitis B. 17,18 Although a DNA virus, HBV replicates via an RNA intermediate. As is seen in human immunodeficiency virus, 19 lamivudine escape mutations in the tyrosine, methionine, aspartate, aspartate (YMDD) locus of the HBV-DNA polymerase are increasingly being reported. [20][21][22][23] While prophylactic failures of HBIG have been treated successfully with lamivudine, there are no reports documenting successful treatment of patients with lamivudine-resistant HBV.Mechanistic evidence suggests that HBIG and lamivudine would be synergistic. By inhibiting viral replication with lamivudine, it would be less likely that the viral binding capacity of HBIG would be overwhelmed; furthermore, there would be little pressure to select for HBIG-resistant mutations in the HBsAg molecule. By providing humoral immunity, HBIG may limit viral spread, confining the virus to extraheAbbreviations: HBV, hepatitis B virus; HBIG, hepatitis B immune globulin; HBsAg, hepatitis B surface antigen; anti-HBs, antibodies against hepatitis B surface antigen; PCR, polymerase chain reaction; HCC, hepatocellular carcinoma; HBeAg, hepatitis B envelope antigen.From

Background Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction without prior advanced liver disease that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. Objective To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. Design Prospective observational cohort study. (ClinicalTrials.gov: NCT00518440) Setting 31 liver disease and transplant centers in the United States. Patients Consecutively enrolled patients–without prior advanced liver disease–with ALF (n = 2070). Measurements Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). Results Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. Limitations The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. Conclusion Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. Primary Funding Source National Institutes of Health.

Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp <20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 g/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio > 2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. In conclusion, conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.

The Model for End-Stage Liver Disease (MELD) score is now the criteria for allocation in liver transplantation for patients with chronic disease. Although the score has been effective in the prediction of mortality in patients awaiting liver transplantation, its abilities to predict posttransplantation outcome need study. The aim of this study is to compare outcome in the first 2 years after liver transplantation according to the pretransplantation MELD score. The study includes 669 consecutive patients who underwent primary liver transplantation between December 1993 and October 1999 in a single transplant center. Patients who died of malignancy were excluded from the series. Pretransplantation MELD score was calculated using the United Network for Organ Sharing formula. Patients were stratified according to MELD score less than 15, 15 to 24, and 25 and higher. Posttransplantation survival at 3, 6, 12, 18, and 24 months was significantly lower in the groups with a higher MELD score. The difference was significant for hepatitis C and noncholestatic liver diseases, but not cholestatic diseases. In patients with a MELD score between 15 and 24, survival was significantly greater with cholestatic diseases and lower in patients with hepatitis C. In our study, pretransplantation MELD score correlates with survival in the first 2 years after transplantation. There is a survival advantage for patients with cholestatic diseases compared with those with hepatitis C. These findings suggest the need to readjust MELD scorebased allocation decisions to consider patient outcome. (Liver Transpl 2003;9:117-123.)