Acetaminophen may be hepatotoxic at therapeutic doses particularly in the case of glutathione depletion and was suggested to aggravate acute viral hepatitis injury. Therefore, acetaminophen might be hepatotoxic in patients with chronic hepatitis C of whom glutathione depletion has been reported. Aim: The aim of this study was to determine the effect of administration of therapeutic doses of acetaminophen on ALT level and viral load (HCV RNA). Patients and methods: We conducted a prospective, randomized double blind study vs placebo. Thirty four patients with chronic hepatitis C, who had elevated serum ALT levels for at least 6 months, a total Knodell score > 5 and who were viremic, received oral doses of acetaminophen (3 gm daily) (Group A; n=17) or placebo (Group P; n=17) for 7 days. Viral load (Monitor HCV Roche) and ALT level were determined before treatment (D0), at the end of treatment (D7), and 3 days after the end of treatment (D10). Results: There was no difference between D0, D7 and D10 in group P (ALAT = 149±75, 141±70, 137±62 IU/L; HCV RNA = 563 735±263 343, 448 617±195 558, 434 647±220 451 copies/mL, respectively) and group A (ALAT = 123±48, 115±44, 119±48 IU/L; HCV RNA = 438 444±114 766, 481 294±175 000, 452 941±125 356 copies/mL, respectively). There was no difference between the two groups at any time. There were no differences 1) in the magnitude of HCV viral load variation 2) in the magnitude of ALT variation, when the phase D0-D7 was compared to the phase D7-D10. In 32 / 34 patients, the variation of the viral load remained < 0.5 log 10. Conclusion: Acetaminophen at therapeutic doses does not affect significantly ALT and HCV RNA levels and can be used as analgesic and antipyretic drug in patients with chronic hepatitis C.97

Binge type alcohol intake is common, especially among young adults. We have previously reported that alcohol bingeing activates Kupffer cells (KC), increases inflammatory cells in liver seen by immunohistology and enhances expression of adhesion molecules on sinusoidal endothelial cells. Despite normal serum aminotransferase (ALT) and routine histology, the changes suggest bingeing may prime the liver for enhanced adverse response to injury. During and following bingeing, persons are at increased risk for events that may cause hypotension and liver ischemia (LI), and also may use pain relieving medications like acetaminophen (ACET). We evaluated whether a single "weekend" alcohol binge altered liver response to LI and ACET. Male SD rats (250-330g; n=5) were binged with alcohol (4g/kg q 12 hrs x 5 doses) or water and 2 hrs after the last dose either given ACET (2.5g/kg i.g.) or under ketamine anesthia subjected to 2 hr partial liver ischemia/reperfusing (I/R). Ischemia was accomplished by atraumatic clamping of the hepatic branch of the portal antrial artery to the median lobe. Sham treated rats had a laporatomy and liver manipulation without clamping. Blood for ALT was drawn 24 hrs after ACET and 4 hrs after clamp removal. Results: Mean serum ALT in binged rats (78 ± 29.1 IU/L) was not different from controls (48 ± 16.2 IU/L; p>0.05). In contrast, mean ALT in alcohol binged rats given ACET (1,238.99 ± 191.23 IU/L) was significantly greater than control rats given ACET (104 ± 18.6 IU/L; p<0.01). Alcohol binged rats having liver I/R also had more necrosis (mean ALT 1,116.28 ± 125.78 IU/L; p<0.01) than sham. Conclusion: Repeated ingestion of large amounts of alcohol over 3 days (a binge) can lower the threshold for liver injury caused by toxicants such as acetaminophen or an episode of ischemia. We speculate that such a mechanism, if recurrent, could lead to "cryptogenic" liver disease.