We propose our characterization of HPV integrated and episomal state is more accurate than previous studies that may have mischaracterized the hybrid HPV-human DNA episomes as integrated. The state of integrated HPV is associated with a poor clinical outcome. Results suggest that the incidence of integrated HPV among all HPV forms peaked and is decreasing. We discuss the importance of our findings for the management of HPV positive head and neck cancer.

Background:The transcription factor 4 (TCF4) locus is one of the most robust association findings

Abbreviations: ALF, acute liver failure; ALI, acute liver injury; ALT, alanine aminotransferase; APAP, acetaminophen; AST, aspartate aminotransferase; AUC, area-under-the-curve; CRRT, continuous renal replacement therapy; HE, hepatic encephalopathy; INR, International Normalized Ratio of the prothrombin time; IQR, interquartile range; LT, liver transplantation; MOSF, multi-organ system failure; NIAAA, National Institute of Alcohol Abuse and Alcoholism; WBC, white blood cells. AbstractBackground & Aims: Non-medical factors which contribute to the severity of acute liver failure (ALF) remain poorly defined. The association of alcohol consumption on the severity of presentation and outcome were determined in patients with ALF and acute liver injury (ALI) in a large, multicentre registry.Methods: Alcohol consumption during the 6 months prior to study entry was analysed in 1170 patients enrolled in the ALF Study Group Registry. Consumption was categorized as none/minimal (<3 alcoholic beverages/week) or at least moderate (≥3/ week). Clinical characteristics, the severity of liver injury at presentation (ALI or ALF) and outcome were compared. Results:In patients with acetaminophen (APAP) overdose, at least moderate alcohol consumption was associated with higher peak aminotransferases, bilirubin, creatinine and INR on admission, compared to no/minimal consumption. In patients with non-APAP ALI/ALF, at least moderate alcohol consumption was associated with higher peak aminotransferases and creatinine. In APAP, non-APAP or all aetiologies, at least moderate alcohol consumption was associated with a 75%, 89% and 82% higher odds, respectively, of presenting as ALF rather than ALI (all P < .005). At least moderate alcohol consumption increased the odds of death by 45% (P = .01) across all aetiologies. In multivariate analysis, older age, non-Caucasian race, peak INR, peak bilirubin and at least moderate alcohol consumption were significantly associated with death. Finally, in Kaplan-Meier analysis of patients with all aetiologies, at least moderate alcohol consumption was associated with decreased time-dependent survival (P = .002). Conclusion:Alcohol consumption adversely affects the presentation and outcome of both APAP-and non-APAP-induced ALI/ALF. K E Y W O R D S acetaminophen, acute liver failure, alcohol, coagulopathy, ethanol, hepatic encephalopathy Handling editor: Dominique Thabut | 361 PURI et al.

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