Persons chronically infected with hepatitis C (HCV) may be at higher risk for developing and dying from non-liver as well as liver cancers than the general population. We therefore assessed cancer incidence and mortality among HCV-infected patients in four large health systems in the United States serving over 1.6 million adults, and compared with rates for the general population during the five-year period from 2006 to 2010. 12,126 chronic HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS) contributed 39,984 person-years of follow-up from 2006 to 2010, and were compared to 133,795,010 records from 13 Surveillance, Epidemiology and End Results Program (SEER) cancer registries, and approximately 12 million US death certificates from Multiple Cause of Death (MCOD) data. Standardized rate ratios (SRR) and relative risk (RR) were calculated for incidence and mortality, respectively. The incidence of the following cancers was significantly higher among patients with chronic HCV infection: liver (SRR, 48.6 [95% CI, 44.4–52.7]), pancreas (2.5 [1.7–3.2]), rectum (2.1 [1.3–2.8]), kidney (1.7 [1.1–2.2]), non-Hodgkin lymphoma (1.6 [1.2–2.1]), and lung (1.6 [1.3–1.9]). Age-adjusted mortality was significantly higher among patients with: liver (RR, 29.6 [95% CI, 29.1–30.1]), oral (5.2 [5.1–5.4]), rectum (2.6 [2.5–2.7]), non-Hodgkin lymphoma (2.3 [2.2–2.31]), and pancreatic (1.63 [1.6–1.7]) cancers. The mean age of cancer diagnosis and cancer-related death was significantly younger in CHeCS HCV cohort patients compared to the general population for many cancers. Conclusions Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population.

Baseline demographic, hospitalization, and mortality data from CHeCS highlight the substantial US health burden from chronic viral hepatitis, particularly among persons born during 1945-1964.

Even in this population with access to care and lengthy follow-up, only a fraction of expected viral hepatitis infections were identified. Abnormal ALT levels often but not consistently triggered testing. These findings have implications for the identification and care of 4-5 million US residents with HBV and HCV infection.

HCV infection is greatly underdocumented on death certificates. The 16 622 persons with HCV listed in 2010 may represent only one-fifth of about 80 000 HCV-infected persons dying that year, at least two-thirds of whom (53 000 patients) would have had premortem indications of chronic liver disease.

In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.