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Delayed HCC Diagnosis in HIV/HCV Coinfected:
HIV not linked to worse liver cancer survival in people with HCV
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Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
HIV infection did not boost the risk of death from hepatocellular carcinoma (HCC) in a study of 339 people with HCV coinfection [1]. Worse HCC stage and HCC diagnosis outside a surveillance program did raise the HCC death risk in this Spanish study.
Some research suggests more aggressive HCC and worse survival after HCC diagnosis in people with HIV infection. But Spanish collaborators who conducted this study proposed that lower survival with HIV in these studies may reflect later HCC diagnosis or lower treatment rates, not HIV infection itself.
To explore these issues they designed a multicenter retrospective cohort study covering the period 1999-2017. They focused on people in the GEHEP-002 cohort (NCT02785835), which recruits HIV-positive people with HCC at 32 centers across Spain. For this analysis the research team selected GEHEP-002 participants also infected with HCV. They created a comparison population of HCC patients infected only with HCV from the liver unit of the Hospital de Valme in Seville. Clinicians managed HCC according to EASL recommendations. They monitored HCC patients every 6 months by abdominal ultrasound.
The analysis included 339 HCC patients with HIV/HCV and 118 with HCV only. The HIV/HCV group was younger than the HCV-only group (median 50 versus 66 years, P < 0.001), included a higher proportion of men (90% versus 67%, P < 0.001) and higher proportions with HCV genotype 3 or 4 (P < 0.001). MELD score and Child-Pugh stage A rates (which assess liver disease severity) did not differ by HIV status.
According to the Barcelona-Clinic Liver Cancer (BCLC) staging system, lower proportions of people with HIV than without HIV had stage 0-A (40% versus 53%) or stage B (8% versus 18%), and higher proportions with HIV had the more advanced stages C (35% versus 23%) or D (17% versus 6%) (P < 0.001). Similar proportions of HCC patients with and without HIV received curative therapies (35% and 41%), noncurative therapies (31% and 24%), and no therapy (34% and 35%). Nonsignificantly higher proportions of HCC patients with than without HIV received HCC treatment in a BCLC staging analysis: stage 0-A (77% with HIV versus 70% without HIV, P = 0.09; stage B, 72% versus 62%, P = 0.5; stage C, 54% versus 41%, P = 0.19).
In the combined study groups, 334 people (73%) died after HCC diagnosis, and 303 of them (66%) died of HCC-related causes. Survival analysis across 36 months found only a marginally lower probability of survival after HCC diagnosis in people with versus without HIV (P = 0.135).
Multivariate analysis did not identify HIV infection as an independent predictor of mortality after HCC diagnosis (adjusted hazard ratio [aHR] 1.07, 95% confidence interval 0.74 to 1.54, P = 0.7). Other variables that did not predict death were age, male sex, more than 50 g of alcohol daily, or lack of previous sustained virologic response to HCV therapy. Three factors did independently predict mortality in this analysis:
-- Worse BCLC HCC stage at diagnosis (P < 0.001):
-- Stage B versus 0-A: aHR 3.31, 95% CI 2.23 to 4.91
-- Stage C versus 0-A: aHR 5.03, 95% CI 3.74 to 6.77
-- Stage D versus 0-A: aHR 9.35, 95% CI 6.41 to 13.64
-- Alpha-fetoprotein (a liver tumor marker) >50 ng/dL: aHR 2.15, 95% CI 1.69 to 2.73, P < 0.001
-- HCC diagnosis outside a surveillance program: aHR 1.36, 95% CI 1.06 to 1.73, P = 0.01
Although HCC mortality was marginally higher in HIV/HCV-coinfected people than in those only with HCV, the GEHEP-002 team proposed, the difference seems related to later HCC diagnosis in people with HIV, not to HIV infection itself or to lower access to HCC therapy. The findings should encourage equal access to HCC treatment in people with HIV.
Reference
1. Merchante N, Fernandez MR, Lopez BF, et al. Impact of HIV on the survival of hepatocellular carcinoma in HCV-infected patients. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 608.
IMPACT OF HIV ON THE SURVIVAL OF HEPATOCELLULAR CARCINOMA IN HCV-INFECTED PATIENTTS
GEHEP-002 investigators and centers:
Nicolás Merchante, Miguel Rodríguez Fernández, Juan Macías, Juan A. Pineda (HU Valme, Sevilla), Esperanza Merino (H. General U. de Alicante), Francisco Rodríguez-Arrondo (HU. Donostia, San Sebastián), Boris Revollo (HU. Germans Trias i Pujol, Badalona), Marta Montero (HU. La Fe, Valencia), María J. Galindo (H. Clínico U. de Valencia), Josefa Muñoz, Sofía Ibarra (H. Basurto, Bilbao), Antonio Rivero-Juárez, Antonio Rivero (HU. Reina Sofía, Córdoba), Joseba Portu (H. Txagorritxu, Vitoria), Marcial Delgado-Fernández (H. Regional U. de Málaga), Miguel García-Deltoro (H. General de Valencia), Ignacio de los Santos (H. La Princesa, Madrid), María José Ríos-Villegas (HU. Virgen Macarena, Sevilla), María Asunción García-Gonzalo (H. de Galdakao, Vizcaya), Koldo Aguirrebengoa (H. de Cruces, Bilbao), Francisco Téllez (HU. de Puerto Real, Cádiz), Carlos Mínguez (H. General de Castellón), María Remedios Alemán-Valls (HU. de Canarias, Santa Cruz de Tenerife), Rosario Palacios, Marina Villalobos (H. Virgen de la Victoria, Málaga), Francisco J. Vera (H. Santa Lucía, Cartagena), Mohamed Omar (CH. de Jaén), Miguel Ángel López-Ruz (H. Virgen de las Nieves, Granada), Carlos Galera (H. Clínico U. Virgen de la Arrixaca, Murcia), Dolores Merino, Miguel Raffo (H. Juan Ramón Jiménez, Huelva), Luis Metola (H. San Pedro, Logroño), Rafael Silvariño (H. San Eloy, Barakaldo).
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