A 64-year-old man is brought to the hospital by ambulance after being found unresponsive by his brother. Despite resuscitative efforts, he dies shortly thereafter. The family reports that the patient had 2 months of progressive fatigue and an unintentional weight loss prior to the episode. Autopsy examination reveals a massive pulmonary embolus, and a cross-section of the liver shows the following: Genomic analysis of the hepatic lesions demonstrates intranuclear fragments of foreign DNA. These fragments most likely belong to which of the following pathogens?

Question

A 64-year-old man is brought to the hospital by ambulance after being found unresponsive by his brother.  Despite resuscitative efforts, he dies shortly thereafter.  The family reports that the patient had 2 months of progressive fatigue and an unintentional weight loss prior to the episode.  Autopsy examination reveals a massive pulmonary embolus, and a cross-section of the liver shows the following:  Genomic analysis of the hepatic lesions demonstrates intranuclear fragments of foreign DNA.  These fragments most likely belong to which of the following pathogens?

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11ec160b_397f_2d81_9249_1710fd49ab4d_MD0001_00 The cross-section of the liver shows a large, solid, yellow-green nodule with multiple smaller nodules, consistent with hepatocellular carcinoma (HCC). Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections dramatically increase the risk of HCC. Ongoing infection with either virus leads to increased hepatocyte turnover and the generation of local inflammatory cytokines, which can result in genetic mutations that lead to malignant transformation. However, HBV has several additional mechanisms that promote HCC, including the following: Integration into the host genome - Nearly 90% of patients with chronic HBV who develop HCC have evidence of HBV DNA in the chromosomes of tumor cells. HBV is a partially double-stranded DNA virus that is repaired by into a closed circular DNA strand. HBV DNA is often inserted into the cellular genome, although this is not required for viral replication (unlike HIV). Integration into regions that control cell growth and differentiation can result in tumorigenesis. Production of oncogenic viral proteins - HBV produces a viral protein called HBx that is a transcriptional activator of several genes associated with cellular growth. It also interferes with the function of p53, an important tumor-suppressor protein. (Choices A and C) Cytomegalovirus and Epstein-Barr virus are members of the Herpesviridae family. Both have double-stranded DNA genomes and cause acute infection followed by latent infection. Cytomegalovirus is not particularly associated with cancer, but Epstein-Barr infection is linked to nasopharyngeal carcinoma and hematologic malignancies. However, neither virus is strongly associated with development of HCC. (Choice B) Entamoeba histolytica is a protozoal infection that is typically acquired by ingesting contaminated food or water in developing countries. A minority of patients develops invasive disease with liver abscess. This usually presents with fever and right-upper quadrant pain. The organism does not incorporate its genome into host cells. (Choice E) Chronic HCV infection dramatically increases the risk of HCC. However, HCV is an RNA virus (that does not have reverse transcriptase) and is unable to integrate into the host genome. (Choice F) Human papilloma virus is a double-stranded DNA virus of the papillomavirus family. HPV produces oncogenic proteins and is able to integrate into the host chromosome. However, HPV is not linked with liver cancer; it typically causes cervical and oropharyngeal cancer. Educational objective: Both hepatitis B (HBV) and hepatitis C virus infections increase the risk of hepatocellular carcinoma due to chronic hepatic inflammation and cell turnover. HBV is also carcinogenic due to the production of oncogenic proteins and the insertion of the HBV genome into host chromosomes. __________ References: Role of hepatitis B virus DNA integration in human hepatocarcinogenesis. (http://www.ncbi.nlm.nih.gov/pubmed/24876744)

A 64-Year-Old Man Is Brought to the Hospital by Ambulance