June 29, 2016
Hepatitis C virus (HCV) and HIV have shared routes of infection. As a result, some people have both infections. This state is called coinfection.
HCV infects the liver, and in cases of chronic infection as the immune system struggles to limit the spread of HCV, inflammation within this organ occurs. Due to ongoing HCV infection and inflammation, healthy liver cells are gradually replaced with useless scar tissue in a process called fibrosis. Eventually fibrosis becomes so extensive that most or all of the liver becomes scarred, a state called cirrhosis. This latter condition increases the risk for complications that can affect general health and other organ-systems such as the kidneys and brain. Internal bleeding and serious infections can occur. People with cirrhosis are at heightened risk for liver failure and, in some cases, liver cancer. Untreated or poorly managed HIV infection can intensify the pace of liver injury in coinfected people.
Research teams in many countries have been conducting studies related to liver health in coinfected people via comprehensive databases. Recently these databases pooled their information so that significant trends that would not be apparent in small datasets could emerge when data from larger numbers of people were analysed. Focusing on the years 2001 to 2014, the researchers found that among 7,229 participants with HIV-HCV coinfection there were 72 cases of liver cancer (about 1%). Furthermore, over the course of the study the risk for liver cancer increased. There were also 375 cases of other liver-related events (serious symptoms or death associated with liver disease); over the course of the study, the risk for these events decreased. Factors linked to an increased risk for liver cancer and other liver-related events included older age, the presence of cirrhosis and low CD4+ cell counts.
Researchers affiliated with the following databases engaged in collaboration for this study:
All participants in the study had antibodies to HCV and were coinfected with HIV.
The researchers defined liver-related events (other than liver cancer) as follows:
The average profile of participants upon entering the study was as follows:
There were a total of 72 cases of liver cancer. Over the course of the study, the risk of liver cancer increased by 11% per year. Bear in mind that while this increase seems large, slightly less than 1% of participants ultimately developed liver cancer. The risk of liver cancer was greatest among people with cirrhosis.
During the study period, the risk for other liver-related events decreased by 4% each year. However, among people with cirrhosis the risk for such problems was very high.
On average, people who developed cancer were about 50 years old.
Although nearly all people received treatment for HIV, the study researchers noted the following:
Around the time that liver cancer was diagnosed, CD4+ cell counts were low, around 286 cells/mm3. Around the time that liver-related events occurred, CD4+ cell counts were also very low, averaging 242 cells/mm3. The reason for such low CD4+ counts is not clear; the study was not designed to explore why cell counts were so low. However, the researchers also found that people who had more than 350 CD4+ cells/mm3 were less likely to develop liver cancer or other liver-related events.
Taking many factors into account, the researchers found that the following were statistically linked to an increased risk for liver cancer:
Most of the same factors (except for HBV coinfection) were also linked to an increased risk for liver-related events.
Several other databases in Spain and the U.S. have reported trends in liver cancer similar to those found in the present study. That is, all of these databases found that the risk of liver cancer rose over time. This increased risk may be generally related to the longer life expectancy that some coinfected people are experiencing due to improved HIV treatment. Unfortunately, longer survival might also allow HCV-related liver inflammation to accumulate, leading to an increased -- yet still quite low -- risk for liver cancer.
The present study has at least one potential shortcoming: It relied on an antibody test to define HCV infection. The issue with this is that antibodies show that the immune system has been exposed to HCV but they do not reveal if the infection is currently active. It is therefore possible that there were some people in the analysis who did not have active HCV coinfection. This could have inadvertently reduced the calculated risks (for liver cancer and other liver-related events).
Historically, treatment for HCV infection would have been a combination of regular injections of interferon and daily oral doses of the broad-spectrum antiviral ribavirin, both drugs usually taken for 48 weeks. At best, these drugs have highly unpleasant side effects and their effectiveness in cases of HIV-HCV coinfection was limited.
However, in recent years in high-income countries potent all-oral HCV medicines called direct-acting antivirals (DAAs) have increasingly become available. These drugs have shown high rates of cure (more than 90%), are generally well tolerated and, in some cases, need only be taken for 12 weeks. As more people with HIV-HCV coinfection become aware of their infection status and enter into care and treatment, it is likely that they will be cured. Consequently, their risk for liver cancer and other liver-related events will decrease, as has been found in large studies in the U.S. and France.
We thank Lars Iversen Gjærde, M.D. from the University of Copenhagen, for his expert review, research assistance and helpful advice.
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