Dramatic increase in incidence of liver cancer in HIV-positive people with viral hepatitis

Incidence of liver cancer among people with HIV has increased dramatically over the past decade, Spanish investigators report in the online edition of Clinical Infectious Diseases. All the cases involved individuals with viral hepatitis co-infection. Prognosis was poor and only a minority of people received potentially curative therapy.

Liver disease is an increasingly important cause of serious illness and death in people with HIV, and is mainly driven by co-infection with hepatitis C virus (HCV). Investigators in Spain wanted to see if incidence of hepatocellular carcinoma (HCC, the most common liver cancer in patients with hepatitis C) was increasing in co-infected people. They therefore analysed data gathered between 1999 and 2010 from 18 hospitals.

A total of 82 cases of liver cancer involving HIV-positive people were identified. All the cases were related to viral hepatitis co-infection: 66 people  (81%) were co-infected with hepatitis C; six (7%) were co-infected with hepatitis B; and ten individuals (12%) were infected with both hepatitis C and hepatitis B.

Only 22 (29%) of the participants infected with hepatitis C had previously received antiviral therapy for this infection. Six of these people achieved a sustained virological response, or SVR, considered a cure. A meta-analysis published in BMJ Open shows that antiviral therapy for hepatitis C reduces the risk of HCC, even in patients who do not achieve a SVR.

The median time between SVR and diagnosis with liver cancer was 28 months.

“This finding reinforces the need to continue performing ultrasound examinations in patients who respond to anti-HCV therapy to rule out HCC,” write the authors.

At the time of diagnosis with liver cancer, 77 people (94%) had evidence of cirrhosis.

The first case of liver cancer was diagnosed in 1999. Thereafter, there was a steady increase in the frequency of such diagnoses, and this increase became dramatic in the last few years.

Some 66 new cases (81%) were diagnosed after 2004.

Incidence of liver cancer related to hepatitis C co-infection was between 0 to 0.6 cases per 1000 person-years before 2003. By 2008-09, incidence had increased to 2.8 cases per 1000 person-years.

The investigators believe this 14-fold increase in the incidence of liver cancer among people co-infected with hepatitis C is “remarkable”.

Most cases of liver cancer were diagnosed late. Only 26 people (32%) had the malignancy detected during routine clinical care. The remaining people were diagnosed after presenting with symptoms.

After diagnosis, 33 participants (40%) received therapy for liver cancer. Of these individuals, eleven received potentially curative therapy (e.g. liver transplant or resection).

Prognosis was poor. Some 65 people (79%) died. Median survival after the diagnosis of liver cancer was just 91 days.

However, mortality rates were significantly lower among people who received potentially curative therapy (29%) compared to those who did not receive such treatment (87%).

There was clear evidence that early diagnosis was associated with an improvement in prognosis. The median duration of survival was 22 months for those whose cancer was diagnosed during routine care, compared to only two months for individuals whose cancer was detected because of symptoms.

“This study suggests that the incidence of HCC is increasing in HIV-infected patients in recent years in Spain,” comment the investigators. “This observation was mainly driven by a notable rise of the incidence of HCC among HIV/HCV-coinfected patients.”

The authors offer several reasons for the dramatic increase in liver cancer:

• Improvements in HIV therapy mean that people co-infected with viral hepatitis are living long enough for liver cancer to develop.

• Hepatitis C therapy has poor efficacy in people co-infected with HIV.

• HIV may accelerate hepatitis C disease progression.

• There have been improvements in the management of liver cirrhosis in co-infected people, resulting in longer survival enabling liver cancer to develop.

“HCC is an emerging complication of chronic liver disease in HIV-infected patients, especially in those who are also infected with HCV,” conclude the authors. “Earlier diagnosis in time to offer potentially curative therapy continues to be the main challenge for clinicians…treatment for HCV infection should also be offered to all potential candidates, in order to achieve SVR, which may prevent the emergence of HCC.”