Anal Dysplasia in Human Immunodeficiency Virus-Infected Men Who Have Sex With Men With Sexually Acquired Early Hepatitis C Virus Infection.

BACKGROUND: Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) are at increased risk of anorectal infection with high-risk human papillomavirus and subsequent high-grade squamous intraepithelial lesions (HSIL), the putative precursor to anal cancer. Recently, an epidemic of sexually transmitted hepatitis C virus (HCV) has emerged that shares this anorectal route of transmission. We hypothesized that the prevalence of anal HSIL would be high in HIV-infected MSM with sexually acquired early HCV infection. METHODS: High-resolution anoscopy (HRA) findings from a cohort of HIV-infected MSM with sexually acquired early HCV infection were compared with HRA findings from a contemporary cohort of HIV-infected MSM without HCV infection who underwent HRA due to abnormal anal cytology found during routine screening. RESULTS: Sixty HIV-infected MSM with sexually acquired early HCV infection and the comparator group of 1150 HIV-infected MSM with abnormal anal cytology but without HCV underwent HRA. The HIV-infected MSM with sexually acquired early HCV had higher CD4 counts compared with the comparator group (656 and 541 cells/µL, respectively; P = .02). Despite this, the prevalence of anal dysplasia was as high among MSM with early HCV as in the comparator group of MSM with abnormal cytology (47 [78%] and 941 [82%], respectively; P = .50), as was the proportion with HSIL (25 [42%] and 379 [33%], respectively; P = .17). CONCLUSIONS: The prevalence of anal dysplasia in HIV-infected MSM with sexually acquired early HCV infection was as high as that of HIV-infected MSM with abnormal anal cytology. These findings suggest that primary screening with HRA may be warranted for HIV-infected MSM with early HCV.

The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study.

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)-based regimens. We performed a retrospective, population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person-years; P = 0.78 and log-rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person-years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank, P = 0.0004). CONCLUSION: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244-2253).

Increased Mitochondrial Genetic Diversity in Persons Infected With Hepatitis C Virus.

BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing. RESULTS: Results were as follows: (1) the average diversity among cases with seronegative acute HCV infection was 4.2 times higher than among uninfected controls; (2) the diversity level among cases with chronic HCV infection was 96.1 times higher than among uninfected controls; and (3) the diversity was 23.1 times higher among chronic than acute cases. In 2 patients who were followed up during combined interferon and ribavirin therapy, mtDNA nucleotide diversity decreased dramatically after the completion of therapy in both patients: by 100% in patient A after 54 days and by 70.51% in patient B after 76 days. CONCLUSIONS: HCV infection strongly affects mtDNA genetic diversity. A rapid decrease in mtDNA genetic diversity observed after therapy-induced HCV clearance suggests that the effect is reversible, emphasizing dynamic genetic relationships between HCV and mitochondria. The level of mtDNA nucleotide diversity can be used to discriminate recent from past infections, which should facilitate the detection of recent transmission events and thus help identify modes of transmission.

Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study.

Outbreaks of acute hepatitis C virus (HCV) infection are occurring in HIV-infected men who have sex with men. We evaluated risk factors and liver histopathology in 11 consecutively enrolled men with newly acquired HCV infection that was diagnosed on the basis of antibody seroconversion, new elevations in alanine aminotransferase level, and wide fluctuations in HCV RNA level. Ten patients reported unprotected anal intercourse, and 7 reported "club-drug" use, including methamphetamine. Liver biopsy showed moderately advanced fibrosis (Scheuer stage 2) in 9 patients (82%). No cause of liver damage other than acute HCV infection was identified. The specific pathways leading to periportal fibrosis in HIV-infected men with newly acquired HCV infection require investigation.