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Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus
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AIDS Oct 1 2021 - Viola Guardignia,M, Alice Toschia,M, Lorenzo Badiaa,Elena Rosselli Del Turcoa, Eleonora Salsib, Francesco Cristinic,Laura Sighinolfid, Gabriele Fabbrie, Marco Massarif, Gianluca Cuomog,Pierluigi Vialea, Gabriella Verucchia, the RECHIV study group
In conclusion, we did find a not negligible rate of HCC occurrence after DAAs in our cohort of HIV/HCV patients with liver cirrhosis, albeit this was not increased when compared with similar population not treated with DAAs. However, our study did confirm the importance of keeping a long-lasting follow-up after HCV eradication in individuals with advanced liver disease.
During a follow-up of 55 months (50–59), we observed 24 patients developing HCC (10.3%), after a median of 22.5 months (IQR 13–32) from DAA regimen initiation, with a calculated HCC incidence of 2.39 event per 100 person-year…..We measured a free from disease survival time of 14 months (IQR 13.5–35.5). Therefore, we found a rate of 9% of de-novo HCC among the overall study sample (21 of 232) and a rate of 50% of recurrence among patients with a history of HCC, after DAAs (3 of 6).
In our study sample, we found a not negligible rate of de-novo HCC following DAAs (9%) and an unexpectedly high rate of recurrence after DAAs (50%, although the number of patients treated for HCV after a first episode of HCC was very small), probably because of the more advanced liver disease and to the longer follow-up duration in comparison to other cohorts [7,8,12].
As expected, a more advanced liver disease (higher CPT score) and a previous HCC were found to be associated with a higher risk to develop hepatocellular carcinoma in our study sample, with an adjusted hazard ratio of 1.51 and 9.87, respectively. Our findings confirmed genotype 3 as a potential risk factor for HCC development, as already demonstrated by other studies that analyzed similar cohorts of HIV/HCV--coinfected people [12,14]. Interestingly, our study showed a protective role of ART (but not of undetectable HIV RNA) at DAA initiation in HCC development, also independently from the other analyzed factors. Consistently with that, 8% of patients who developed HCC were not taking ART at the time of our evaluation, because of their elite controller status, defined as ability to spontaneously keep their plasma HIV RNA below quantifiable levels for several years.
The lack of a control group of HCV monoinfected patients treated with DAAs or untreated represents the main limitations of our study, although we used similar experiences in our country to make comparisons. In addition, we have to acknowledge the retrospective nature and the amount of missing data.
The advent of IFN-free regimens based on DAAs has completely changed the scenario of HCV treatment, with an extremely high rate of HCV eradication and an expected impact in the natural history of HCV infection as well [10]. However, conflicting data on HCC occurrence after HCV therapy have been emerged since the use of DAAs in monoinfected HCV patients, with some studies even suggesting an increased risk for HCC in these individuals [7,8]. Consistent data regarding HCC risk among people coinfected with HIV and HCV after DAAs treatment are scarce. However, thus far, DAAs do not seem to affect HCC occurrence, with HCC rates similar to those in pre-DAA era both for de-novo occurrence [10] and for recurrence [11]. In detail, Hasson et al.[11] described a de-novo HCC rate of 2.5% among 118 patients with advanced liver disease treated for HCV and an overall frequency of HCC of 0.88% was reported by Merchante et al.[12] after SVR with DAA-IFN-free regimens in a cohort of PWH with cirrhosis. Furthermore, Merchante et al.[12] showed a 74% reduction in HCC risk in those with compensated cirrhosis treated with DAAs when compared with no therapy in patients with similar clinical characteristics, with five events among 260 individuals who received IFN-free therapy.
Abstract
Objectives:
Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population.
Design:
We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017.
Methods:
We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer.
Results:
During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/μl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline.
Conclusion:
Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.
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