Hepatitis C virus infection: See beyond the liver

Parag Mahale, The University of Texas School of Public Health


Background: Chronic hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC) and specific subtypes of non-Hodgkin lymphomas (NHLs). Several studies have demonstrated associations between HCV infection and other cancers, but the associations have not been systematically assessed in elderly US population. HCV is also associated with several extrahepatic manifestations (EHMs), but data on the effect of antiviral therapy (AVT) on the risk of EHMs are sparse. ^ Methods: To answer the first question, we conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in US adults aged ≥ 65 years. Cases (n=1,623,538) were people with first cancers identified in SEER registries (1993-2011). Controls (n=200,000) were randomly selected cancer-free individuals frequency-matched to cases on age, sex, race, and year of diagnosis/selection. We identified HCV diagnosis before cancer diagnosis/control selection using Medicare claims. We determined the adjusted associations between HCV infection and cancers using logistic regression models. To answer the second question, We conducted a retrospective cohort study using data from the VA HCV Clinical Case Registry in patients who were identified with a positive HCV RNA test between 10/1999 and 8/2009 with follow-up through 1/2010. AVT with interferon ± ribavirin was identified. Sustained virological response (SVR) was defined as negative HCV RNA at least 12 weeks after end of AVT. Risk of 8 incident EHMs were evaluated: type-II mixed cryoglobulinemia (MC), glomerulonephritis (GN), porphyria cutanea tarda (PCT), lichen planus (LP), B-cell non-Hodgkin lymphoma (NHL), type-2 diabetes mellitus (T2DM), coronary heart disease (CHD), and stroke. Separate multivariable Cox regression models were built with AVT±SVR as a time-varying exposure. ^ Results: HCV infection was positively associated with cancers of the anus (adjusted odds ratio [aOR]=1.97; 95%CI=1.42-2.73), liver (aOR=31.51; 95%CI=28.96–34.28), intrahepatic (aOR=3.40; 95%CI=2.52–4.58) and extrahepatic (aOR=1.90; 95%CI=1.41-2.57) bile ducts, pancreas (aOR=1.23; 95%CI=1.09-1.40), non-melanoma non-epithelial skin (aOR=1.53; 95%CI=1.15–2.04), myelodysplastic syndrome (aOR=1.56; 95%CI=1.33-1.83), and diffuse large B cell lymphoma (aOR=1.57; 95%CI=1.34-1.84); and negatively associated with uterine (aOR=0.64; 95%CI=0.51–0.80) and prostate (aOR=0.73; 95%CI=0.66–0.82) cancers. Of 160,875 patients included in the second study, 31,143 (19.4%) received AVT, of which 10,575 (33.9%) experienced SVR. EHMs evaluated were rare, with lower incidence rates observed among AVT+SVR group when compared to untreated patients. Significant reduction in risk of EHMs were observed in AVT+SVR group when compared to untreated patients for MC (adjusted hazard ratio [aHR]=0.63; 95%CI=0.40-0.97), GN (aHR=0.52; 95%CI=0.41-0.66), PCT (aHR=0.40; 95%CI=0.20-0.81), NHL (aHR=0.66; 95%CI=0.44-0.97), T2DM (aHR=0.83; 95%CI=0.77-0.90), and stroke (aHR=0.83; 95%CI=0.74-0.93). ^ Conclusions: HCV infection is associated with increased risk of cancers other than HCC in the US elderly population. Risks of some EHMs of HCV infection are reduced after AVT+SVR. Early initiation of AVT after HCV diagnosis should be considered to maximize the potential benefits of AVT.^

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Recommended Citation

Mahale, Parag, "Hepatitis C virus infection: See beyond the liver" (2016). Texas Medical Center Dissertations (via ProQuest). AAI10127419.