Exploring the risks of liver cancer after successful treatment for hepatitis C virus

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1 CATIE-News CATIE s bite-sized HIV and hepatitis C news bulletins. Exploring the risks of liver cancer after successful treatment for hepatitis C virus 11 June 2013 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 HIV-positive men who have sex with men (MSM) having unprotected anal intercourse particularly when blood or STIs are present, 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. 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

2 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

3 participants who did achieve an SVR. Factors linked to liver cancer Age was one factor statistically linked to the development of liver cancer. People who were older than 50 years were at increased risk for this cancer compared to younger people. People who were 60 years old were at even greater risk than younger people. This heightened risk with age is a factor of the time that someone has been infected with HCV (older people are more likely than younger people to have had HCV for a longer time). The longer a person has HCV, the greater the chances of liver damage and for abnormal liver cells to be transformed into cancer cells. The other factor linked to an increased risk of cancer was being male. Liver-related complications The risk for developing any liver-related complications was very low among participants who achieved an SVR. The main complication was ascites an accumulation of fluid in the abdomen. Among people who did not achieve an SVR or who were untreated, the risk for developing liver-related complications was elevated. Survival Overall, 10% (11 people) of participants with an SVR died during the course of the study. Four of these deaths were from complications due to liver cancer. The other causes of death included other cancers, such as those affecting the lungs and pancreas gland, as well as causes unrelated to cancer, such as infections. Among participants who did not develop an SVR or who were not treated, 22% (52) died from liver-related causes. The importance of an SVR The findings from the Swedish study underscore the general importance of achieving an SVR with HCV treatment. Not only does this event mean that HCV has been cleared but it reduces the future risk for developing liver-related complications and improves the chances of survival among people with cirrhosis. HCV and liver health Some previous studies have found that scarred liver tissue can partially regress and healthy tissue can regenerate after an SVR. It would have been interesting to assess the possibility of a link between the amount of scarred liver tissue and the future risk of developing liver cancer. However, in the present study researchers did not assess changes in the liver to determine whether or not scar tissue had regressed. What is clear from the present study is that achieving an SVR helps to clear HCV infection and improves future chances of survival. However, an SVR does not mean that damaged liver tissue disappears. People with cirrhosis who have achieved an SVR will likely need regular monitoring to keep abreast of any developing tumours. Long-term studies are also needed to help doctors determine which of their patients with cirrhosis who have achieved an SVR are at heightened risk for developing liver cancer. Resources hepcinfo.ca CATIE s hepatitis C website What is liver cancer? Canadian Cancer Society REFERENCES: Sean R. Hosein 1. Canadian Cancer Society s Steering Committee on Cancer Statistics. Canadian Cancer Statistics Toronto, ON: Canadian Cancer Society; Koh C, Heller T, Haynes-Williams V, et al. Long-term outcome of chronic hepatitis C after sustained virological response to interferon-based therapy. Alimentary Pharmacology & Therapeutics May;37(9):

4 3. van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA Dec 26;308(24): Aleman S, Rahbin N, Weiland O, et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clinical Infectious Diseases. 2013; in press. 5. Pereira OC, Feld JJ. Sustained virologic response for patients with hepatitis C-related cirrhosis: a major milestone, but not quite a cure. Clinical Infectious Diseases. 2013; in press.

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