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Exploring the Risks of Liver Cancer After Successful Treatment for Hepatitis C Virus

June 11, 2013

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In Canada and other high-income countries, in the 1970s and '80s hepatitis C virus (HCV), hepatitis B virus (HBV) and later HIV and other germs were sometimes transmitted via transfusion of contaminated blood and use of products derived from contaminated blood (such as clotting factors). However, thanks to screening of the blood supply, transmission of HCV, HBV and HIV via blood or blood products is virtually non-existent in Canada and similar countries today.

At present, HCV transmission most commonly occurs in Canada through the following means:

  • sharing equipment for substance use, such as needles, syringes, straws and rolled-up currency notes
  • reusing unsterile equipment for tattooing and body piercing
  • among men who have sex with men (MSM) -- having unprotected anal intercourse, sharing unsterilized sex toys, and not using a new condom with each new partner

Newcomers to Canada are also at risk for complications from HCV and/or HBV if they come from regions where these viruses are relatively common, where reuse of needles may have occurred in mass vaccination campaigns, or where the blood supply has been contaminated or medical equipment may not have been sterilized.

HCV infects the liver. Initially there may be no symptoms or mild symptoms of infection similar to the flu. As a result, many people may not be aware that they have HCV. Once HCV infection becomes established in the liver, it slowly degrades the functioning of this vital organ. Over time, healthy liver tissue is replaced by damaged (scarred) tissue in a process called fibrosis. Eventually, serious complications can occur, including liver failure and in some cases liver cancer. According to a recent report from the Canadian Cancer Society, while cases of many cancers are stable or declining, cases of liver cancer are on the rise. Unfortunately, there is no vaccine against HCV. For these reasons and more, it is important to get tested for hepatitis C, engage in behaviours to prevent HCV transmission, and, if infected, get care and treatment. Other ways to reduce liver cancer risk include screening for hepatitis B virus (HBV) and, if infected, getting treatment. HBV is spread in ways similar to HCV. Uninfected people can speak to their doctor about vaccination against HBV.

A key goal of treatment for HCV is to quickly suppress the amount of virus in the blood and to keep it as low as possible. Achieving and maintaining very low levels of HCV in the blood (viral load) is critical to recovery from HCV and curing this infection.

The duration of treatment for HCV depends on several factors, including the strain of HCV (called the genotype), the presence of co-infections such as HIV, and so on. However, what all approved treatment regimens have in common is that for recovery from HCV to occur, patients must have what is called a sustained virological response (SVR) for 24 weeks after treatment has ended. If the amount of HCV in the blood is not extremely low (undetectable), recovery is unlikely.


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The Damage Left Behind

Most clinical trials of HCV treatment have monitored patients up to or shortly after they have completed their SVR. This amount of time is generally sufficient to assess the effectiveness of treatment. However, longer studies are needed to assess changes in liver health and monitor the risk for liver cancer. The reason for such additional studies is that while effective HCV treatment appears to cure this infection, such treatment, particularly if given in the latter stages of HCV disease, does not wholly reverse the damage that has occurred to the liver. So although HCV is cured, some degree of liver damage and consequent liver disease remains.

To explore the consequences of liver damage in HCV-positive people with cirrhosis (severe liver damage), infectious disease and liver specialists in Sweden conducted a study. They enrolled 351 HCV-infected people who had severe liver damage. Some participants received HCV treatment and were cured of this infection. Subsequent monitoring found that cases of liver-related complications, liver-related deaths and liver cancer were "markedly reduced" after SVR was achieved, compared to participants who did not achieve an SVR or who were not treated. However, the researchers found that a long-term risk for liver cancer remained in their study participants, even in some of those with an SVR. Further findings from this study appear later in this CATIE News bulletin.


Study Details

Researchers enrolled participants with HCV between January 2001 and July 2009 from six hospitals across Sweden. For the present analysis, they focused on 351 participants from their study whose basic profile at the start of the study was as follows:

  • 69% men, 31% women
  • age -- 51 years
  • presence of type 2 diabetes -- 20%
  • 50% had genotype 1 HCV
  • viral load -- 1 million copies
  • 6 participants were co-infected with HIV
  • 6 participants were co-infected with hepatitis B virus

Common features and/or consequences of liver disease in all participants were as follows:

  • severely damaged livers (cirrhosis). This diagnosis was based on liver biopsy results or a combination of blood tests, signs/symptoms of liver-related complications and/or CT and MRI scans suggestive of cirrhosis
  • a buildup of fluid in their abdomen because of elevated blood pressure in the liver's arteries
  • internal bleeding
  • problems with memory and thinking clearly, caused by the buildup of toxins in the blood

Therapy for HCV infection during the study was a combination of interferon and ribavirin.

On several occasions after SVR occurred, participants' blood samples were assessed and retested to confirm continued SVR. Viral load tests used after 2006 had a lower limit of detection of 15 IU/ml.


Results

Among the 351 participants, responses to HCV therapy were as follows:

  • 31% were treated and achieved an SVR
  • 55% were treated but did not achieve an SVR

The remaining 14% of participants were untreated (the reasons for this were not disclosed).


Liver Cancer After SVR

Liver cancer was diagnosed with the help of CT scans. In total, six (5%) out of 110 participants who achieved an SVR subsequently developed liver cancer over an average observation period of five years. In two cases, the diagnosis of liver cancer occurred less than a year after SVR was achieved. This suggests that the cancer had been present for some time -- and was likely present during treatment when it went undiagnosed.


Liver Cancer in People Without SVR

Among participants who did not experience an SVR, cases of liver cancer were at least twice as high as among participants who did achieve an SVR.

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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News. Visit CATIE's Web site to find out more about their activities, publications and services.
 

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