Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Real-life experience with sorafenib for the treatment of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To report the real-life results of sorafenib use in a cohort of HIV-infected patients with hepatocellular carcinoma (HCC). METHODS: The GEHEP-002 cohort (ClinicalTrials.gov ID: NCT02785835) has recruited 302 HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. RIS-HEP12 study included 44 (14%) cases that have received at least one dose of sorafenib. The overall survival after the start of treatment was the main efficacy outcome. Permanent discontinuation due to adverse events was the primary safety end point. RESULTS: Reasons for sorafenib use are HCC recurrence after previous curative therapy (n = 7), progression following transarterial chemoembolization (n = 6) and first treatment against HCC (n = 31). Nineteen (43%) patients harbored Child-Pugh B cirrhosis. Barcelona-Clinic Liver Cancer stage was A 3 (7%), B 6 (14%), C 30 (68%) and D 5 (11%). All patients were on antiretroviral therapy (ART). The median (Q1-Q3) duration of sorafenib treatment was 70 (31-158) days. Median survival was 7.2 months, whereas the median (Q1-Q3) duration of overall survival after the start of treatment was 4 (2-9.7) months. Twenty-six (59%) patients had any grade adverse events and 19 (43%) suffered a decompensation. Discontinuation due to adverse events occurred in 17 (38.6%) patients. There were no modifications or discontinuations of ART. CD4 cell counts and HIV viral load remained stable. CONCLUSION: The efficacy of sorafenib under real-life conditions in HIV-infected patients seems lower than that reported in the registration clinical trial. On the contrary, the tolerability of sorafenib appears to be similar to what is seen in patients without HIV infection. Sorafenib does not seem to modify the efficacy of ART.

Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain.

BACKGROUND: To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS: Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.