No abstract

Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

Liver disease complicates human immunodeficiency virus (HIV)/acquired immune deficiency syndrome; however, liver pathology data are limited, particularly from high HIV prevalence countries. We investigated the spectrum and clinicopathological correlates of liver pathology in a high HIV burden setting. In a single-center study, all HIV/acquired immune deficiency syndrome patients with complete clinical and demographic data who underwent liver biopsy were analyzed and clinicopathologically assessed by hepatologists and one of two experienced liver pathologists. We evaluated 301 patients, with a median age of 34 (interquartile range 29-40) years. Women (n 5 143) were younger than men (n 5 158), with a median age of 33 (interquartile range 28-37) versus 35 (interquartile range 31-41) years, P 5 0.001. The majority, 76.1%, were black African. Median CD4 at time of biopsy was 127 (52-260) cells/mm 3 . Drug-induced liver injury was the predominant finding (42.2%), followed by granulomatous inflammation (29%), steatosis/ steatohepatitis (19.3%), hepatitis B (19%), and hepatitis C coinfection (3.3%), with more than one pathology in 16.2%. With granulomatous inflammation, 52% met the criteria for tuberculosis immune reconstitution syndrome. By univariate analysis, cotrimoxazole and antiretroviral therapy conferred risk for drug injury (odds ratio [OR] 5 2.78 [1.72-4.48], P < 0.001; OR 5 1.69 [1.06-2.68], P 5 0.027). In multivariate analysis, cotrimoxazole was associated with a cholestatic or ductopenic injury (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).89], P < 0.001; OR 5 17.6 [3.26-95.3], P < 0.0001); efavirenz was associated with nonspecific hepatitis or submassive necrosis (OR 5 4.3 [1.92-9.83], P < 0.001; OR 5 10.46 [2.7-40.5], P < 0.001). Cholestatic injury was associated with female gender and a CD4 of >200 cells/mm 3 , and submassive necrosis was associated with younger age. Hepatitis B demonstrated no association. Conclusion: In a high HIV burden area, drug-induced liver injury due to antiretroviral therapy and cotrimoxazole was a frequent clinicopathological finding; Mycobacterium tuberculosis was the leading opportunistic infection, with more than half of patients fulfilling criteria for tuberculosis immune reconstitution syndrome; liver biopsy remains a useful diagnostic procedure in this setting. (HEPATOLOGY 2015;61:1721-1729