Liver cancer has a more aggressive disease course in HIV-positive people co-infected with viral hepatitis

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Co-infection with HIV and viral hepatitis is associated with a more aggressive disease course for liver cancer, according to research conducted in London and presented to the recent EASL Monothematic Conference: HIV and the Liver.

The investigators found that liver cancer developed at an early age in co-infected people, that there was a high dropout rate when waiting for liver transplant, and that overall survival was poor.

The research has implications for HIV care, with the investigators calling for more surveillance of liver cancer in co-infected people.

Glossary

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

spleen

Organ which produces white blood cells and acts as a reservoir for red blood cells.

 

hypertension

When blood pressure (the force of blood pushing against the arteries) is consistently too high. Raises the risk of heart disease, stroke, kidney failure, cognitive impairment, sight problems and erectile dysfunction.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

referral

A healthcare professional’s recommendation that a person sees another medical specialist or service.

Large numbers of people with HIV are co-infected with hepatitis B and/or hepatitis C. Liver disease is now a leading cause of illness and death in those co-infected people. An important manifestation of liver disease in this group is hepatocellular carcinoma (HCC). Research conducted in Spain recently found increased rates of HCC in HIV-positive people, especially in the context of hepatitis C co-infection. Investigators from King’s College Hospital, London, wished to establish a clear understanding of HCC in their HIV-positive patients.

They therefore conducted a case-controlled study. Individuals who developed HCC between 2003 and 2010 were identified from hospital records and matched with HIV-negative controls who also developed HCC.

A total of 20 cases of HCC involving people with HIV were identified; 13 cases of HCC were diagnosed in people co-infected with hepatitis C, and seven cases were diagnosed in hepatitis C-co-infected individuals.

Almost all (n = 19) the participants were men and their median CD4 cell count was 249 cells/mm3. The majority (n= 19) were taking antiretroviral therapy. Most had well-controlled HIV infection, and viral load was undetectable in 18 participants (80%).

HCC developed at a younger age in the HIV-positive people compared to the controls (46 vs 58 years; p < 0.0001).

The malignancy was diagnosed as part of routine care for twelve of the co-infected people. Almost all (n = 18) the HIV-positive participants had liver cirrhosis at the time their HCC was detected.

Staging of liver disease and HCC at the time of diagnosis did not differ significantly between the patients and the controls.

There were a number of differences between the participants co-infected with hepatitis B compared to those co-infected with hepatitis C.

People co-infected with HIV and hepatitis C had lower CD4 cell counts than those with HIV and hepatitis B (180 vs 430 cells/mm3; p = 0.06), and also had more advanced portal hypertension (spleen size: 15 vs 11 cm; p = 0.02).

Comparison between HIV-positive and HIV-negative people with hepatitis C infection showed that individuals with HIV were significantly less likely to have undergone a course of hepatitis C therapy (14 vs 73%; p = 0.006).

Management of HCC did not differ significantly between the HIV-positive and the HIV-negative participants.

However, although six of the co-infected patients were referred for liver transplant, only three individuals actually underwent the procedure.

Survival was poorer in the participants with HIV than the controls. Only 17% of the co-infected individuals were alive five years after the diagnosis of HCC; this compared to a 41% survival rate in the HIV-negative patients.

The 24-month survival rate was significantly poorer in the HIV/hepatitis B co-infected patients compared to the hepatitis B-monoinfected controls (39 vs 61%; p = 0.03).

Mortality rates twelve months after diagnosis of HCC among the participants with hepatitis C were poor in both co-infected and monoinfected individuals (43 vs 32%).

“HIV-positive patients with HCC present at younger age, have a high drop-out rate for liver transplant and appear to have a more aggressive disease course,” conclude the investigators. “Heightened HCC surveillance may be warranted.”

References

Joshi D et al. Hepatocellular carcinoma in HIV-positive patients: a more aggressive disease course? EASL Monothematic Conference: HIV and the Liver, London, 2012.