Michael P. Manns, MD
As the treatment of hepatitis C evolves, so does the treatment of hepatocellular carcinoma (HCC). With most hepatitis C infections now responding positively to novel agents such as simeprevir (Olysio) and sofosbuvir (Sovaldi), as well as several combination therapies, understanding how the virus impacts HCC risk and recurrence without a control group has become more complex. Further challenges arise in understanding how liver transplantation and advanced disease are impacted by hepatitis C treatment in patients with HCC.
For expert insight on the relationship between advances in hepatitis C care and the future of HCC treatment, OncLive
spoke with Michael P. Manns, MD, director, Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover in Germany.OncLive: How common is hepatitis C as a cause of liver cancer? Dr Manns
: Hepatitis C is a main cause of HCC, in addition to hepatitis B and alcohol. A prerequisite to HCC is the development of liver cirrhosis; almost all patients with hepatitis C–associated cancer have liver cirrhosis. In Japan, 65% of all patients with liver cancer have hepatitis C. In Europe, it is also heavily linked to liver cancer, with alcohol as the second most likely cause.What are the main goals in treating HCC?
Prevention is key. We know that preventing or reversing cirrhosis is the best way to prevent liver cancer development. Once it occurs, we need to treat the early stages by locoregional therapies or surgery. Then, clearance of the hepatitis C virus should be significant in reducing the risk of recurrent disease. If you cure the virus before cirrhosis develops, that is key. Finally, we need to eradicate the hepatitis C entirely and that may be difficult without a vaccine, but we are on the right track. Another issue in hepatitis C prevention is accessibility and cost. However, the building blocks to solve this are available.How has the treatment of hepatitis C changed in recent years?
Previous treatment for hepatitis C, which was mostly limited to ribavirin and interferon, was 1-year long and full of side effects and drug interactions with HCC treatments. Now, the new direct-acting antiviral agents have high cure rates of more than 90%, almost no side effects, and only take on an average of 12 weeks to administer.
It is interesting to see how fast the field of hepatitis C is moving. Most of the data are still from the interferon days, so we need to really revaluate everything, especially since these new agents and combinations have been approved. What questions remain unanswered in the treatment of hepatitis C–associated liver cancer?
For patients who can receive curable therapies for hepatitis C who already have HCC, clearing the virus reduces the risk of recurrent disease. However, we are missing data for patients in palliative treatment for advanced disease. We are unsure of the impact clearing hepatitis C in that population has on liver cancer.
Moreover, it is important to take note of patients with hepatitis C who receive a transplant. In the past, reinfection has been universal, and recurrent hepatitis C had very inferior outcomes compared to other indications for liver transplantation. Therefore, the first goal should be to get the hepatitis C population after transplantation free of hepatitis C and prevent reinfection.
We need to determine whether and to what extent hepatitis C treatment can prevent cancer. This is particularly relevant in those with liver cirrhosis. In the past, this was easier to prove because only half of those treated for hepatitis C responded to treatment and we could compare responders to nonresponders. Now with cure rates at almost 90% for hepatitis C, we have very few nonresponders. Therefore, the control group would be hard to find. It is unethical to not treat for hepatitis C, so I think treating for hepatitis C will be recommended in the future. The message should be: if you clear the virus, the risk of liver cancer is significantly reduced.
We may need to develop new strategies for surveillance of patients who have been treated for hepatitis C. We know that increased age is associated with risk of having high-alpha one fetoprotein.Are there patients with HCC who should not be treated for hepatitis C?
If the HCC prognosis is very inferior and survival is not likely, then treating for hepatitis C may not be beneficial. We do not know if treating hepatitis C could be detrimental to some patients at this time, so that is something that needs to be considered with each advanced patient.