Liver Stiffness-Based Strategies Predict Absence of Variceal Bleeding in Cirrhotic Hepatitis C Virus-Infected Patients With and Without Human Immunodeficiency Virus Coinfection After Sustained Virological Response.

BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.

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.

IL7RA rs6897932 Polymorphism is Associated with Better CD4+ T-Cell Recovery in HIV Infected Patients Starting Combination Antiretroviral Therapy.

Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4+ recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4+ T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4+ T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4+ T-cells count <200 cells/mm3. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4+ T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy-Weinberg equilibrium (p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4+ T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4+ T-cells increase (AMR = 1.19; p = 0.004), and higher CD4+ T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4+ T-cells at the end of follow-up ≥500 CD4+ cells/mm3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of ≥ 400 CD4+ cells/mm3 lost statistical significance (p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4+ T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4+ T-cells count <200 cells/mm3.

Higher relapse rate among HIV/HCV-coinfected patients receiving sofosbuvir/ledipasvir for 8 vs 12 weeks.

OBJECTIVES: To compare the efficacy of sofosbuvir/ledipasvir (SOF/LDV) for 8 weeks (SL8) versus a 12-week course of SOF/LDV (SL12) among HIV/HCV-coinfected patients in clinical practice. In addition we compared sustained virological response (SVR) rates achieved with SL8 in HCV-monoinfected and HIV/HCV-coinfected patients in a real life setting. METHODS: HCV-infected patients were retrospectively selected from the HEPAVIR-DAA and GEHEP-MONO real-life prospective cohorts if they fulfilled the following criteria: 1) Infected with genotype 1; 2) Treatment with SL8 or SL12; 3) Treatment naïve prior to receiving SL8 or SL12; 4) Absence of cirrhosis; 5) Baseline HCV RNA<6 × 106 IU/mL; 6) Reached the scheduled time-point for SVR (SVR12) assessment. SVR12 and relapse rates of HCV-monoinfected and HIV/HCV-coinfected patients were compared on an intention to treat basis. The responses with SL8 and SL12 were also compared. RESULTS: In the SL8 group, 107 (51%) HCV-monoinfected and 102 (49%) HIV/HCV-coinfected patients were included. One hundred and sixty-four (43%) HCV-monoinfected subjects and 220 (57%) HIV/HCV-coinfected patients received SL12. SVR12 rates for HIV/HCV-coinfected patients treated with SL8 vs SL12 were SVR12 92.2% vs. 97.3% (p = 0.044) and the respective relapse rates were 4.9% vs. 0.5% (p = 0.013). SVR12 rates for SL8 among HCV-monoinfected and HIV/HCV-coinfected patients were: 96.3% vs. 92.2% (p = 0.243), respectively. The corresponding relapse rates were 0.9% vs. 4.9% (p = 0.112). CONCLUSION: HIV/HCV-coinfected patients reach high rates of SVR12 with SL8, although lower than with SL12, mainly due to a higher probability of relapse. SVR12 rates with SL8 are numerically lower and the proportion of relapses higher in HIV/HCVcoinfected patients than in HCV-monoinfected subjects.

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.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.