People with hepatitis C have higher cancer rates, even when excluding liver cancer

Anders Nyberg of Kaiser Permanente San Diego. Photo by Liz Highleyman,
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Hepatitis C patients in the Kaiser Permanente Southern California health maintenance organisation had significantly increased cancer rates compared to members without HCV infection, researchers reported at the European Association for the Study of the Liver (EASL) 50th International Liver Congress last month in Vienna, Austria. This remained the case even after accounting for liver cancer, which showed the greatest excess risk.

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC), a type of liver cancer. But the effects of HCV infection elsewhere in the body are not fully understood. Chronic hepatitis C has been linked to cardiovascular disease, diabetes and several other conditions including non-Hodgkin's lymphoma; its association with other kinds of cancer is unknown.

Anders Nyberg of Kaiser Permanente San Diego and colleagues conducted a retrospective analysis comparing cancer rates among people with hepatitis C in their cohort and health plan participants without hepatitis C.


person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.


A type of cancer that starts in the tissues of the lymphatic system, including the lymph nodes, spleen, and bone marrow. In people who have HIV, certain lymphomas, such as Burkitt lymphoma, are AIDS-defining conditions.

non-Hodgkin lymphoma

A group of lymphomas (cancers of the lymphatic system). The many types of non-Hodgkin lymphoma (NHL) are classified according to how fast the cancer spreads. Although the symptoms of NHLs vary, they often include swollen lymph nodes, fever, and weight loss. Certain types of NHLs, such as Burkitt lymphoma and immunoblastic lymphoma, are AIDS-defining cancers in people with HIV.


A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

Kaiser Permanente Southern California (KPSC) is a large health maintenance organisation with more than 3 million members. The KPSC cancer registry (affiliated with the US National Cancer Institute's SEER registry) maintains a complete profile of all cancer diagnoses among Kaiser Permanente members.

This analysis looked at all cancer diagnoses among adult patients with or without hepatitis C between January 2008 and December 2012. During this period, the analysis included 35,712 people in the HCV cohort and 5,297,191 people the non-HCV cohort. People with HIV and people with a history of solid organ or bone marrow transplants were excluded.

The HCV cohort was younger (approximately 60 vs 72 years) and included a higher proportion of men (about 60% vs about 50%) than the non-HCV cohort. Compared to the non-HCV cohort, people with hepatitis C were more likely to have other cancer risk factors including tobacco smoking (about 70% vs 30%), heavy alcohol use/abuse (about 15% vs 2%), diabetes (about 25% vs 8%) and higher body mass index. Seventy-two per cent of HCV patients diagnosed with cancer, 35% of HCV patients without cancer and 7% of people in the non-HCV cohort had liver cirrhosis.

According to the published study abstract, cancer diagnosis rates were 1524 per 100,000 person-years in the HCV cohort compared to 605 per 100,000 person-years in the non-HCV cohort. When liver cancer was excluded, the corresponding cancer rates were 1139 and 601 per 100,000 person-years, respectively. Liver cancer accounted for 25% of all cancers in the HCV cohort but only 7% in the non-HCV group.

People in the HCV cohort had significantly higher rates of several types of cancer, typically with a two-fold to four-fold increased risk:

  • Colon-rectum: relative risk (RR) 1.88
  • Prostate: RR 2.05
  • Lung: RR 2.44
  • Oesophagus: RR 2.51
  • Head-neck: RR 2.56
  • Pancreas: RR 2.79
  • Stomach: RR 3.03
  • Kidney: RR 3.05
  • Myeloma: RR 3.41
  • Non-Hodgkin's lymphoma: RR 3.59.

Not surprisingly, liver cancer showed the greatest excess risk in the HCV cohort, with a nearly a 68-fold increased risk (RR 68.67). For all sites including liver cancer, the relative risk was 2.33, falling to 1.84 for all sites except the liver.

People with HCV had an increased risk for many cancers even in the absence of smoking, heavy alcohol use and diabetes. The differences were smaller after stratifying for these other risk factors, but remained significant for overall cancer, liver cancer and non-Hodgkin's lymphoma.

"In our cohort of hepatitis C infected patients, cancer rates were significantly increased compared to the non-HCV cohort," the researchers concluded. "This suggests that another extra-hepatic manifestation of HCV may be an increased risk of cancer."

Regarding the mechanisms by which HCV infection contributes to cancers beyond the liver, Nyberg suggested at an EASL press conference that this may be related to chronic inflammation or the virus' effects on oncogenes (cancer-causing genes) and tumour-suppression genes.

However, noting the influence of other risk factors, he stressed that we cannot assume that HCV is actually the cause of cancers other than HCC. In the presence of confounding factors, HCV may have only a moderate effect, he explained. "Adding HCV to smoking doesn't add to the risk much, but for a non-smoker HCV has a larger effect," he said.

"Increased cancer rates are likely multifactorial," Nyberg continued. "The take-home message is that we can take HCV out of the equation by treating it for three months, then we can work on lifestyle factors that may take more time."

He added that Kaiser Permanente currently has no restrictions on which hepatitis C patients are eligible for antiviral therapy and he recommends treatment for everyone.

"We can wait for studies showing whether HCV treatment reduces cancers, including HCC, but my preference is to treat now," he concluded.


Nyberg AH et al. Increased cancer rates in patients with chronic hepatitis C: an analysis of the cancer registry in a large U.S. health maintenance organization. EASL 50th International Liver Congress, Vienna, abstract O058, 2015.