Euro-Canadian study looks at trends in liver cancer in co-infected people

Want to receive publications straight to your inbox?

Hepatitis C virus (HCV) and HIV have shared routes of infection. As a result, some people have both infections. This state is called co-infection.

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 co-infected people.

Research teams in many countries have been conducting studies related to liver health in co-infected 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 co-infection 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.

Study details

Researchers affiliated with the following databases engaged in collaboration for this study:

  • EuroSIDA
  • Southern Alberta Clinic Cohort
  • Canadian Co-infection Cohort
  • Swiss HIV Cohort

All participants in the study had antibodies to HCV and were co-infected with HIV.

The researchers defined liver-related events (other than liver cancer) as follows:

  • brain dysfunction (hepatic encephalopathy)
  • kidney injury and dysfunction arising from HCV-related liver dysfunction
  • build-up of fluid in the abdomen
  • internal bleeding from varicose veins
  • bacterial infections in fluid that had built up in the abdomen

The average profile of participants upon entering the study was as follows:

  • age – 38 years
  • 68% men, 32% women
  • 388 CD4+ cells/mm3
  • 6% had cirrhosis
  • 5% of participants were infected with three viruses: HIV, HCV and hepatitis B virus (HBV)

Results—Focus on liver cancer

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.

Results—Other liver-related events

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.

Factors linked to liver cancer

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:

  • the presence of cirrhosis
  • being older
  • triple infection with HBV
  • a lower current CD4+ cell count

Most of the same factors (except for HBV co-infection) were also linked to an increased risk for liver-related events.

Compare and contrast

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 co-infected 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.

Bear in mind

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 co-infection. This could have inadvertently reduced the calculated risks (for liver cancer and other liver-related events).

Changes to HCV treatment

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 co-infection 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 co-infection 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.

Resources

Acknowledgement

We thank Lars Iversen Gjærde, MD from the University of Copenhagen, for his expert review, research assistance and helpful advice.

—Sean R. Hosein

REFERENCES:

  1. Gjærde LI, Shepherd L, Jablonowska E, et al. Trends in incidences and risk factors for hepatocellular carcinoma and other liver events in HIV and hepatitis C virus co-infected individuals from 2001 to 2014: a multi-cohort study. Clinical Infectious Diseases. 2016; in press.
  2. Lawitz E, Ruane P, Stedman C, et al. Long-term follow-up of patients with chronic HCV infection following treatment with direct-acting antiviral regimens: maintenance of SVR, persistence of resistance mutations and clinical outcomes. The International Liver Congress, 13-17 April 2016, Barcelona. Abstract 166.
  3. Carat F. Clinical outcomes in HCV-infected patients treated with direct-acting antivirals—18 months post-treatment follow-up in the French ANRS CO22 Hepather cohort study. The International Liver Congress, 13-17 April 2016, Barcelona. Abstract LBP 505.