Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended. (HEPATOLOGY 2005;42:1364-1372

In patients with chronic hepatitis C, alcohol consumption has been proposed as a risk factor for the progression of liver disease; however, evidence for this remains conflicting. Two hundred thirty-four anti-hepatitis C virus (HCV)-positive patients who had a liver biopsy performed within the past 24 months were studied. Demographic data and information on risk factors were recorded. A detailed lifetime alcohol consumption history was obtained. Viral studies included HCV viral titer and HCV genotype. Mean age (؎ SEM) of the group was 40.8 ؎ 0.7 years. One hundred sixty-six (71%) were male. A risk factor for HCV infection was found in 195 patients (86%). Genotype distribution was: 1b: 22%; 1a: 15%; 1(nonsubtypable): 15%; 3a: 34%; and 2: 7%. Fifty (21%) patients had cirrhosis. Patients with cirrhosis were older (51.6 ؎ 1.8 years) than those with chronic hepatitis (37.6 ؎ 0.6 years; P ‫؍‬ .0001), were infected at an older age (25.9 ؎ 2.0 vs. 20.9 ؎ 0.6 years; P ‫؍‬ .001), and had a longer duration of infection After exposure to hepatitis C virus (HCV), over 70% of persons will fail to clear the infection and become chronic carriers. These individuals develop chronic hepatitis of varying severity.

Serum concentrations of alpha-fetoprotein (AFP), variably elevated during liver injury, have been suggested to be of prognostic importance in acute liver failure (ALF), higher values being associated with improved outcome. Using a nephelometric assay, we measured AFP in sera obtained on admission from 206 patients prospectively enrolled in the US ALF Study, and on day 3 in 162 of these patients. The AFP ratio was defined as the day 3 AFP concentration divided by that observed on day 1. Median (range) admission serum AFP in all patients was 8.1 (1-1,811) ng/mL and increased to 17.6 (1.1-1,162) ng/mL on day 3 (P Ͻ 0.001). Higher absolute levels were not associated with improved outcome. In fact, admission AFP levels were lower in survivors not receiving transplants than in those who died or were transplanted (P Ͻ 0.001), whereas there was no difference between the 2 groups on day 3 (P ϭ 0.34). However, a rise in AFP values between day 1 and day 3 indicated a better prognosis: the AFP ratio was 2.2 (0.11-22.1) in spontaneous survivors and 0.87 (0.11-16.4) in nonsurvivors (P Ͻ 0.001). An increasing AFP level indicated by an AFP ratio Ն1 was observed in 70 of 98 (71%) survivors, whereas a ratio Ͻ1 was observed in 51 of 64 (80%) nonsurvivors. In conclusion, AFP values change dynamically during ALF. In this large prospective study, higher absolute values of AFP did not predict a favorable outcome, but a rising level of AFP over the first 3 hospital days frequently indicated survival.