No abstract

The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were studied, giving special attention to alcohol history, time between overdose and intravenous N-acetylcysteine (NAC) treatment ("time to NAC"), and other data available at the time of admittance. Up until 72 hours after ingestion, time to NAC was the single most important independent risk factor. With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1.78-6.97). Acute alcohol ingestion was an independent protective factor regarding mortality in alcoholic patients (OR, 0.08; 95% CI, 0.01-0.66) but not in nonalcoholic patients (OR, 0.21; 95% CI, 0.03-1.67). Patient age and quantity of acetaminophen were independent risk factors. In conclusion, time to NAC was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due to an increased risk of developing hepatotoxicity should be treated with NAC regardless of risk estimation. (HEPATOLOGY 2002;35:876-882.)

An increase in alpha-fetoprotein (AFP) following hepatic necrosis is considered indicative of hepatic regeneration. This study evaluated the prognostic value of serial AFP measurements in patients with severe acetaminophen-induced liver injury. Prospectively, serial measurements of AFP were performed in 239 patients with acetaminophen intoxication and a peak alanine aminotransferase (ALT) level above 1,000 U/L. AFP was measured using an enzymelinked immunoassay (EIA) with a detection limit below 0.4 g/L. The optimum threshold of AFP to discriminate nonsurvivors was identified. An increase in AFP above 4 g/L occurred in 158 (79%) of 201 survivors compared with 11 of 33 nonsurvivors (33%; P < .00001). The increase in AFP occurred a mean of 1.0 days (range, ؊2 to ؉6 days) after peak ALT in survivors compared with 4.1 days (range, ؉2 to ؉7 days) in nonsurvivors (P < .00001). Starting on the day of peak ALT, AFP values were significantly higher in survivors than in nonsurvivors. A threshold AFP of 3.9 g/L on day ؉1 after peak ALT to identify nonsurvivors had a sensitivity of 100%, a specificity of 74%, a positive predictive value of 45%, and a negative predictive value of 100%. In conclusion, an increase in AFP was strongly associated with a favorable outcome in patients with acetaminophen-induced liver injury. AFP may be useful as a supplement to existing prognostic criteria. We suggest that the introduction of highly sensitive EIAs for the detection of AFP will require a reevaluation of AFP as a prognostic marker in acute nonneoplastic liver disease. (HEPATOLOGY 2005;41:26 -31.)

The aim of the study is to evaluate the effect of a single treatment with the molecular adsorbents recirculating system (MARS) on systemic hemodynamics and oxygen consumption (VO 2 ) in patients with hyperacute liver failure (HALF). In a controlled design, eight patients with HALF were assigned to a 6-hour MARS treatment, and five patients, to a control group that was mechanically cooled to match the MARS group. Systemic hemodynamic variables were determined hourly during the study period. In the MARS group, systemic vascular resistance index increased by 46% from 1,215 ؎ 437 to 1,778 ؎ 710 dynes ⅐ s ⅐ cm ؊5 ⅐ m ؊2 (P < .0001), which significantly exceeded a 6% increase in the control group. Mean arterial pressure increased from 69 ؎ 5 to 83 ؎ 11 mm Hg in the MARS group (P < .0001) and was unchanged in the control group. Cardiac index decreased by 20% from 4.6 ؎ 1.8 to 3.7 ؎ 1.1 L/min ⅐ m ؊2 (P ‫؍‬ .0007) in the MARS group and by 7% in the control group. Heart rate decreased from 105 ؎ 21 to 85 ؎ 15 beats/min in the MARS group (P < .0001) and was unchanged in the control group. In the MARS group, oxygen delivery decreased from 621 ؎ 198 to 486 ؎ 141 mL/min ⅐ m ؊2 (P < .05), and VO2, from 142 ؎ 31 to 112 ؎21 mL/min ⅐ m ؊2 (P < .05). Arterial lactate and pH levels were unchanged. In conclusion, systemic hemodynamic values tend to normalize, whereas systemic VO 2 decreases during MARS treatment in patients with HALF. These effects cannot be explained by the degree of cooling associated with MARS. (Liver Transpl 2003;9: 290-297.)

Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospectively, serial measurements of serum phosphate were performed in 125 patients with severe acetaminophen poisoning. The optimum threshold value of serum phosphate to discriminate nonsurvivors was identified. Prognostic value and speed of identification were compared with those of the King's College Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 ؎ 1.18 mmol/L vs. 0.68 ؎ 0.22 mmol/L, P < .001) as well as 72 to 96 hours after overdose (2.12 ؎ 0.22 mmol/L vs. 0.59 ؎ 0.23 mmol/L, P < .001). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than the KCH criteria, and it identified patients significantly earlier after transferal [median 1 hour (range 1-38 hours) vs. 12 hours (2-192 hours), P < .05, respectively]. In nonsurvivors, the degree of hyperphosphatemia correlated with renal dysfunction (R ‫؍‬ .55; P ‫؍‬ .02). In conclusion, hyperphosphatemia after acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a highly specific as well as sensitive predictor of nonsurvival. We propose that hyperphosphatemia is caused by renal dysfunction in the absence of hepatic regeneration, as the latter appears to be associated with lowering of serum phosphate. (HEPATOLOGY 2002;36:659-665.)