Influence of language barrier and cultural background in hepatitis B disease knowledge in a Chinese community of Spain.

Introduction: Hepatitis B infection (HBV) is prevalent in China. Due to language barriers and cultural differences, it is not always straightforward to evaluate disease knowledge in liver clinics. We aimed to assess the awareness on HBV and its mechanisms of transmission in HBV-infected Chinese patients and their household contacts. Methods: HBV-infected Chinese patients and their contacts were interviewed by a native Chinese nurse regarding their knowledge on HBV transmission mechanisms, use of preventive measures and vaccination status. Non-Chinese HBV-infected patients and their household contacts served as a control group. Results: In total 182 patients and 398 contacts participated with 85 (47%) patients and 240 (60%) contacts being from China. Language barrier was reported in 80% of Chinese patients and 44% of their contacts. Knowledge on parenteral and sexual HBV transmission was high in all patients (~90%) but Chinese were more aware of vertical transmission than controls (94% vs. 68%; p < 0.01). Regarding the use of preventive measures, Chinese patients were more forewarned in their use to avoid parenteral transmission (93% vs. 74%, p < 0.01). When assessing household contacts, Chinese used preventive measures more frequently than controls for parenteral and sexual transmission (79% vs. 65 and 81% vs. 48%, p < 0.05). Vaccination coverage was slightly lower in Chinese contacts compared to controls (78% vs. 86%, p = 0.05). Conclusion: Despite relevant language barriers, Chinese patients are well informed on the mechanisms of HBV transmission. Cultural differences may explain a higher use of preventive measures among the Chinese population. HBV vaccination of household contacts should be reinforced in both groups.

Clinical profile of Spanish hepatitisC virus-infected treatment-naïve patients with compensated cirrhosis in the CREST study. / Perfil clínico de los pacientes españoles con hepatitisC naïve con cirrosis compensada tratados en el estudio CREST.

BACKGROUND AND AIM OF THE STUDY: There are still patients with hepatitisC in Spain who have yet to be diagnosed, but their clinical profile is unclear. In 2021, 21.93% of patients diagnosed had cirrhosis and were mostly treatment-naïve. METHODS: This sub-analysis describes the clinical profile of the 60Spanish treatment-naïve patients with compensated cirrhosis who were included in the CREST study. MAJOR RESULTS: Sixty percent of patients were male, median age 56years, and 33% had a history of drug use. Almost three-quarters (71.3%) had more than one comorbidity and 78.3% took concomitant medication. At treatment initiation, median platelet count was 139×103/µL and FibroScan® 17kPa. No virological failure was observed and no patient discontinued treatment due to adverse events. No clinically significant changes were noted during or after treatment in the median platelet, albumin, bilirubin, and transaminase levels. CONCLUSIONS: Treatment with glecaprevir/pibrentasvir for 8weeks in this cohort of treatment-naïve patients with compensated cirrhosis in Spain was safe and effective. This information reinforces the use of this short antiviral regimen even when there is compensated cirrhosis, simplifying the approach to hepatitisC among those patients still to be diagnosed and treated in Spain.

Anticancer drugs are the first cause of drug-induced liver injury in a reference hospital.

Drug-induced liver injury (DILI) is a challenging liver disorder for hepatologists. We aimed to assess the pattern and causes of DILI in a tertiary hospital. We registered prospectively all patients referred with suspicion of DILI from 2018 to 2023. A total of 106 patients fulfilled the diagnostic criteria (30 caused by paracetamol were excluded; total number 76). The pattern of liver injury was hepatocellular in 55 (72%). Drugs causing DILI were antineoplastic (26%), antibiotics (24%), analgesics (12%), and recreational drugs (9%). Regarding clinical outcomes, 39 (51%) required hospitalization and 7 (9%) underwent a liver transplantation or died from acute liver injury. We identified 126 additional patients with DILI due to immune check-point inhibitors who were not referred to a liver disease specialist. Antineoplastic drugs have become the first cause of DILI in hospitals. A multidisciplinary approach and specific educational tools to increase DILI awareness are needed among different specialists.

Health-Related Quality of Life in Patients Living with Wilson Disease in Spain: A Cross-Sectional Observational Study.

Wilson disease (WD) is a rare copper metabolism disorder caused by mutations in the ATP7B gene. It usually affects young individuals and can produce hepatic and/or neurological involvement, potentially affecting health-related quality of life (HRQoL). We assessed HRQoL in a cohort of Spanish patients with WD and evaluated disease impact on several domains of patients' lives, treatment adherence, drug preference and satisfaction, and healthcare resource utilisation in a cross-sectional, retrospective, multicentric, observational study. A total of 102 patients were included: 81.4% presented isolated liver involvement (group H) and 18.6% presented neurological or mixed involvement (group EH). Up to 30% of patients reported a deteriorated emotional status with anxiety and depression, which was greater in the EH subgroup; the use of neuropsychiatric drugs was high. Over 70% of the patients were satisfied with their current treatment but complained about taking too many pills, stating they would consider switching to another more patient-friendly treatment if available. The Simplified Medication Adherence Questionnaire revealed only 22.5% of patients were fully adherent to therapy, suggesting that alternative therapies are needed. This real-world study, even though is highly enriched with hepatic patients and mild disease, shows that WD impacts patients' HRQoL, especially in the emotional domain.

Benefits of using exchangeable copper and the ratio of exchangeable copper in a real-world cohort of patients with Wilson disease.

Wilson disease (WD) is a complex disease in which diagnosis and long-term metabolic copper control remains challenging. The absence of accurate biomarkers requires the combination of different parameters to ensure copper homeostasis. Exchangeable copper and its ratio (REC) have been suggested to be useful biomarkers in this setting. We aimed at introducing these measurements and evaluate their performance and accuracy in our real-world cohort of WD patients. Exchangeable copper and REC were measured in 48 WD patients and 56 control individuals by inductively coupled plasma-mass-spectrometry. Demographic and clinical characteristics were collected. REC was shown to be significantly higher among WD patients compared to controls and useful for WD identification by using the previously established cutoffs: 71.4% of WD patients with a recent diagnosis had REC ≥18.5% and 95.1% of long-term treated WD had REC ≥14%; only four patients of the cohort presented discordant levels. Moreover, REC values were below 15% in all the control individuals. Exchangeable copper was significantly higher in WD patients compared to controls and tended to be reduced among WD patients who were compliant to medication. This real-life study confirmed that exchangeable copper and REC are useful serum biomarkers that can be used as complementary tests to ensure WD diagnosis (REC) and copper homeostasis whithin time (exchangeable copper). The desirable target levels for this last objective still needs to be validated in prospective cohorts.

Recent advances in the diagnosis and management of Wilson's disease.

In this editorial, the reader will be updated on novel epidemiological, diagnostic, and therapeutical proposals in the field of Wilson disease.

Low risk of viral hepatitis amongst patients with severe mental disorders.

BACKGROUND AND AIMS: Patients with severe mental disorders (SMD) have been classically considered as a particularly high-risk population for bloodborne virus infections. We performed a systematic screening of hepatitis B and C virus among the population with SMD in the area of influence of Hospital Clínic (Barcelona) in order to evaluate the real prevalence of these infections and achieve HCV microelimination in this subpopulation. METHODS: We screened two cohorts for anti-HCV and HBsAg: Cohort A (hospitalized patients with SMD, done systematically) and Cohort B (outpatients, mental health centre-CSMA, done voluntarily). Risk factors and socio-demographic variables were collected. In positive cases, telematic review was activated by Hepatology, calculation of FIB-4 and prescription of direct-acting agents (DAA) in HCV or follow-up in HBV. RESULTS: In Cohort A, 404 patients were screened. 3 HBV patients were detected (0.7%). In all of them, there was a history of drug use. 12 anti-HCV positive patients were detected (3%); 8 of them had a history of drug use. Among the HCV positive, only 2 patients were viraemic (received DAA, both achieving SVR) as most of them (n = 6) had already been cured with DAA. In cohort B, 305 patients were screened, after 542 (64% of the target population) declined to participate. No cases of HCV or HBV were detected. CONCLUSIONS: HCV/HBV prevalence among SMD population with no history of drug use does not seem to be different from the general population. These data may be of interest for defining health policies.

HCV microelimination in harm reduction centres has benefits beyond HCV cure but is hampered by high reinfection rates.

Background & Aims: Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices. Methods: On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment. Results: Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness. Conclusions: HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates. Lay summary: People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.

Considerations for optimizing Wilson's disease patients' long-term follow-up. / Enfermedad de Wilson: consideraciones para optimizar el seguimiento a largo plazo.

Wilson's disease is a sistemic genetic disease caused by the excessive accumulation of copper. The first and main involvement is in the liver, which can range from mild and transient elevation of transaminases to the onset of an overt cirrhosis or acute liver failure. It is known that up to 20-30% of these patients may evolve to liver cirrhosis during follow-up. In clinical practice, liver fibrosis is assessed mainly by using indirect and non-invasive tools (laboratory tests, liver elastography, ultrasound), similar to other prevalent chronic liver diseases. However, despite the fact that liver elastography is a valuable tool in general hepatology, the evidence of its usefulness and accuracy in Wilsons disease is scarce. This review summarizes the available scientific data and their limitations in Wilson's disease.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

OBJECTIVE: The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration. DESIGN: We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson. RESULTS: Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). CONCLUSION: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules.

BACKGROUND & AIMS: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population. METHODS: We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months. RESULTS: A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified. CONCLUSIONS: Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs. LAY SUMMARY: Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.

Elastography is unable to exclude cirrhosis after sustained virological response in HCV-infected patients with advanced chronic liver disease.

BACKGROUND: Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)-infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown. AIMS: To evaluate TE accuracy at identifying cirrhosis 3 years after HCV-eradication. METHODS: Prospective, multi-centric study including HCV-cACLD patients before direct-acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated. RESULTS: Among 746 HCV-infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non-invasive tests (APRI and FIB-4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV-genotype 3 (20.81 (2.12-201.47), .009), and TE before treatment (1.21 (1.09-1.34), <.001) were the only variables associated with cirrhosis after SVR. However, the accuracy of TE after SVR was poor (AUROC = 0.75) and 6 (27.3%) out of 22 patients with a TE <8 kPa had cirrhosis. Similar results were found with APRI and FIB-4 scores. CONCLUSIONS: Cirrhosis is present, 3 years after SVR, in more than half of HCV-cACLD patients even with the normalisation of liver function parameters, serological non-invasive tests and TE values. The low diagnostic accuracy of non-invasive methods after SVR reinforces the need for long-term surveillance.

Risk of non-tumoural portal vein thrombosis in patients with HCV-induced cirrhosis after sustained virological response.

BACKGROUND & AIMS: Sustained virological response (SVR) to direct-acting antivirals ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analysed the long-term impact of SVR on the development of non-tumoural PVT. METHODS: Our study comprised of two well-characterized prospective cohorts (hepatitis C virus '(HCV)-Cured': n = 354/'HCV-Active': n = 179) of patients with HCV cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoural PVT and events known to modify its natural history (orthotopic liver transplantation, transjugular intrahepatic portosystemic shunt, death, tumoural PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis. RESULTS: Ten (2.8%) patients in the 'HCV-Cured' cohort developed a non-tumoural PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the 'HCV-Active' cohort were diagnosed with non-tumoural PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoural PVT development and stage A patients were at low risk. Importantly, HCV cure did not decrease the risk of non-tumoural PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio: 1.31 (95% confidence interval [95% CI]: 0.43-3.97); P = .635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 [95% CI: 0.287-0.715]; P < .001). CONCLUSIONS: The risk of non-tumoural PVT persists after HCV cure in patients with cirrhosis, despite improving survival. Even after aetiological cure, severity of liver disease remains the main determinant of non-tumoural PVT development.

Efficacy of an accelerated double-dose hepatitis B vaccine regimen in patients with cirrhosis.

The hepatitis B (HBV) vaccine is recommended in unvaccinated adults with cirrhosis, despite its low efficacy. We aimed to evaluate the response to a double-dose/accelerated vaccine schedule in patients with cirrhosis admitted into a hepatology ward. All patients with cirrhosis admitted to the hepatology ward without exclusion criteria were offered the HBV HBVAXPRO 40mcg vaccine at months 0, 1 and 2. Non-responders received a second cycle. We evaluated 468 patients and only 19% were seroprotected against HBV. In 196 patients without exclusion criteria for HBV vaccination, the per protocol response rate (anti-HBs >10 U/ml) was 23% after a first cycle and 59% after a second cycle. The overall response per intention to treat was only 23%. We have not identified predictors of response. Only one patient had a mild adverse event. Most patients with cirrhosis admitted in the hepatology ward are unprotected against HBV. Although a second HBV vaccination cycle increases the response rate, the poor overall response reinforces the implementation of HBV vaccination before the development of cirrhosis.

Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy.

A significant proportion of patients infected with SARS-CoV-2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL-6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID-19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti-HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow-up was available in 61 patients: 72% were male, median age was 67 years, and anti-HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow-up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV-DNA (<15 IU/mL). Both were anti-HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow-up after hospital discharge is unfeasible in patients without anti-HBs, a short course of antiviral prophylaxis may be a safe option.

Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients.

BACKGROUND & AIMS: Factors associated with a successful outcome upon nucleos(t)ide analogue (NA) treatment withdrawal in HBeAg-negative chronic hepatitis B (CHB) patients have yet to be clarified. The objective of this study was to analyse the HBV-specific T cell response, in parallel with peripheral and intrahepatic viral parameters, in patients undergoing NA discontinuation. METHODS: Twenty-seven patients without cirrhosis with HBeAg-negative CHB with complete viral suppression (>3 years) were studied prospectively. Intrahepatic HBV-DNA (iHBV-DNA), intrahepatic HBV-RNA (iHBV-RNA), and covalently closed circular DNA (cccDNA) were quantified at baseline. Additionally, serum markers (HBV-DNA, HBsAg, HBV core-related antigen [HBcrAg] and HBV-RNA) and HBV-specific T cell responses were analysed at baseline and longitudinally throughout follow-up. RESULTS: After a median follow-up of 34 months, 22/27 patients (82%) remained off-therapy, of whom 8 patients (30% of the total cohort) lost HBsAg. Baseline HBsAg significantly correlated with iHBV-DNA and iHBV-RNA, and these parameters were lower in patients who lost HBsAg. All patients had similar levels of detectable cccDNA regardless of their clinical outcome. Patients achieving functional cure had baseline HBsAg levels ≤1,000 IU/ml. Similarly, an increased frequency of functional HBV-specific CD8+ T cells at baseline was associated with sustained viral control off treatment. These HBV-specific T cell responses persisted, but did not increase, after treatment withdrawal. A similar, but not statistically significant trend, was observed for HBV-specific CD4+ T cell responses. CONCLUSIONS: Decreased cccDNA transcription and low HBsAg levels are associated with HBsAg loss upon NA discontinuation in patients with HBeAg-negative CHB. The presence of functional HBV-specific T cells at baseline are associated with a successful outcome after treatment withdrawal. LAY SUMMARY: Nucleos(t)ide analogue therapy can be discontinued in a high proportion of chronic hepatitis B patients without cirrhosis. The strength of HBV-specific immune T cell responses may contribute to successful viral control after antiviral treatment interruption. Our comprehensive study provides in-depth data on virological and immunological factors than can help guide individualised therapy in patients with chronic hepatitis B.

Improvement of sexuality after hepatitis C cure with direct acting antivirals.

Despite rarely assessed, sexuality is a relevant domain in Quality of Life. We prospectively evaluated the impact of direct-acting antiviral therapy on sexuality in a cohort of 186 patients with chronic hepatitis C (HCV). Sexual dysfunction was assessed by validated scales CSFQ-14/CSFQ-VAS at baseline and one year after treatment finalization. Median age was 55 years and 87% had mild liver disease. Basal prevalence of sexual dysfunction (62%) and fear of HCV transmission (25%) were high. After HCV cure, both sexual dysfunction prevalence and CSFQ-VAS improved (P = .058 and P < .01, respectively), and fear of HCV transmission dropped to 16% (P = .02). These changes were especially relevant in young men (<55), where sexual dysfunction decreased from 48.6% to 29.7% (P = .04) and among non-depressed patients in whom sexual dysfunction decreased from 54.6% to 47% (P < .01). Age and major depression remained as independent factors of sexual dysfunction persistence after HCV cure. Our data suggest that HCV eradication is associated with an improvement in sexuality, in those patients without depression.

Chronic genotype 1 hepatitis C along with cirrhosis drives a persistent imprint in virus-specific CD8+ T cells after direct-acting antiviral therapies.

Chronic hepatitis C virus (HCV) infection impairs HCV CD8+ T-cell responses, while it could influence immune responses towards unrelated viruses/vaccines (e.g. cytomegalovirus, CMV, and influenza, Flu). The aim of our study was to delineate whether restoration of these virus-specific CD8+ T cells occurs after direct-acting antiviral (DAA) therapies and particularly in patients with cirrhosis. We performed longitudinal analysis (baseline, week 4, follow-up [FU] 12 and FU48) of virus-specific CD8+ T cells by multicolour flow cytometry in HCV-cirrhotic patients undergoing DAA therapy (n = 26) after in vitro expansion with immunodominant HCV, CMV and Flu epitopes restricted by HLA-A*02. HCV noncirrhotic patients (n = 9) and healthy individuals (n = 10) served as controls. We found that the proliferative capacity of HCV-specific CD8+ T cells increased from baseline up to FU48 in a significant proportion of cirrhotic and noncirrhotic patients. Nevertheless, these cells remained poor cytokine producers in both patient groups, regardless of the down-regulation of inhibitory co-regulatory receptors in HCV-cirrhotic patients at FU48. Likewise, high expression levels of these exhaustion markers were detected in CMV-/Flu-specific CD8+ T cells in HCV-cirrhotic patients at all time points, albeit without affecting their proliferative capacity or cytokine production. We conclude that DAA therapies induce restoration of the proliferative capacity of HCV-specific CD8+ T cells. However, these cells remain phenotypically and functionally impaired. Contrarily, the 'exhausted' phenotype in CMV-/Flu-specific CD8+ T cells in HCV-cirrhotic patients did not associate with their functions. Larger studier with longer follow-up may elucidate whether this complex interplay influences the outcome of cirrhotic patients.