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Background Antibiotics could modify multidrug-resistant microorganisms (MDRO) populations in urban wastewater. Water treatment plays a major role in their control. This study aimed to explain the characteristics of multidrug-resistant Gram-negative bacteria in the wastewater of a city in southern Spain, the reduction achieved by treatment and the influence of human antibiotic prescriptions. Methods We collected 24-hour composite water samples from four wastewater treatment plants (WWTPs) over one year (2021-2022) and cultured them quantitatively. All acquired ESBL/carbapenemase isolates were sequenced and genomes were compared with those of clinical isolates. Linear mixed model regression analyses were performed to assess the WWTP effect and the association with human antibiotic prescriptions. Findings Aeromonas predominated among the MDROs and KPC-2 was the main carbapenemase detected in the influents. The 44% and 30% of E. coli and K. pneumoniae influent isolates, respectively, belonged to high-risk clones; 10·6% of Enterobacteriaceae could be matched to clinical isolates and a strain from a current hospital outbreak was found in raw samples. WWTPs reduced ESBL and carbapenemase producers by 1·4-log and 1·8-log, respectively. New MDROs and persistence of certain strains were detected in effluents. Quinolone and cephalosporin prescriptions, flow-rate and population density were associated with higher OXA-48 producer counts. Interpretation Despite the reduction, additional technologies should be implemented in WWTPs receiving hospital discharges. Due to the predominance of environmental species, culture and metagenomic approaches should be combined to differentiate human and sewages origin for antibiotic resistance monitoring. Antibiotic stewardship could be a strategy to reduce the release of MDROs.

[Objective] To investigate the impact of COVID19 pandemic on the incidence of health-care associated Clostridioides difficile infection (HA-CDI)., [Methods] Retrospective study conducted in the Hospital Universitario de Valme (HUV) and the Hospital General Universitario de Alicante (HGUA) in Spain between January 2019 and February 2021. The study period was divided into non-COVID19 period (2019 and months from 2020 to 2021 with ≤30 hospitalized COVID19 patients) and COVID19 period (months from 2020 to 2021 with >30 COVID19 patients). HA-CDI incidence rates (IR) were calculated as the number of new CDI cases per 10.000 occupied bed-days (OBD) and antimicrobial consumption by means of the defined daily dose (DDD) per 1000 OBD., Results] During the COVID19 period, HA-CDI IR in the HUV was 2.6 per 10.000 OBD, which was lower than what was observed during the non-COVID19 period (4.1 per 10.000 OBD; p = 0.1). In the HGUA, HA-CDI IR during COVID19 period was 3.9 per 10.000 OBD, which was not significantly different to the IR observed during the non-COVID19 period (3.7 per 10.000 OBD; p = 0.8). There was a slight increase in the total antibiotic consumption during COVID19 period in both hospitals, with significant increases of certain high-risk antibiotics as cephalosporins., [Conclusions] HA-CDI incidence has not increased during the COVID19 pandemic in two tertiary centers in Spain, in spite of a slightly higher antibiotic consumption during the COVID19 period in both hospitals. These findings suggest that, in the presence of strict infection control measures, hospital antibiotic consumption might have a lower impact than expected on HA-CDI.

[Background] The aim of this study was to describe the natural history of acute Q fever, including its clinical and serological evolution and progression to chronic Q fever., [Methods] Observational cohort study (January 2011–September 2020) performed at Valme University Hospital (Seville, Spain). Inclusion criteria: (1) patients aged ≥18 years; (2) acute Q fever diagnosis, defined as suggestive symptoms in the presence of phase II immunoglobulin G (IgG) titer >1:256; (3) at least 6 months’ follow-up after the acute Q fever episode. The incidence of seroconversion to a chronic Q fever serological pattern, defined as phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis, was assessed., [Results] During the study period, 117 patients were included. Thirty-four (29%) patients showed phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis. All patients with classic serological criteria for chronic Q fever diagnosis remained asymptomatic despite no specific treatment, with a median (quartile 1–quartile 3 [Q1–Q3]) follow-up of 26.5 (14–44) months in this subgroup. No cases of Q fever endocarditis nor other persistent focalized infection forms were observed during the study period., [Conclusions] A significant proportion of acute Q fever patients develop classic serological criteria for chronic Q fever diagnosis in the absence of additional data of chronic Q fever. Consequently, phase I IgG cutoff titers >1:800 should not be used as a criterion to consider such a diagnosis. The incidence of persistent focalized infection forms after acute Q fever is extremely low and does not justify the use of prophylaxis strategies.

[Background] The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention., [Methods] The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020–March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein–1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated., [Results] One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04–0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences., [Conclusions] IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

[Objectives ] To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin., [Methods] Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed., [Results] Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06–0.29; P < 0.0001] whereas exposure for ≥5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4–27.1; P < 0.0001)., [Conclusions] Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

[EN] The micro-elimination of HCV infection in drug users (DU) in our area is a priority in order to achieve the overall elimination of this disease. Coordinated action between specialists in addiction treatment, microbiologists and physicians who treat HCV infection is required to implement infection screening, to achieve universal access to treatment and to prevent new infections and reinfections. The objective of this document was to come to a consensus on the screening, hospital referral, treatment, follow-up and prevention of HCV infection in DU by an expert panel from GEHEP/SEIMC and three scientific societies of addiction treating physicians: SEPD, SOCIDROGALCOHOL and SOMAPA., [ES] La microeliminación de la infección por VHC en pacientes usuarios de drogas (UD) es una prioridad para lograr la eliminación global de esta enfermedad. Se requiere una acción coordinada de especialistas en el tratamiento de adicciones, microbiólogos y médicos que tratan la infección por VHC para realizar el cribado de los pacientes, garantizar el acceso al tratamiento y prevenir nuevas infecciones y reinfecciones. El objetivo de este documento fue consensuar las medidas de cribado, envío a unidades hospitalarias, tratamiento, seguimiento y prevención de la infección por VHC en UD, por parte de un panel de expertos de GEHEP/SEIMC y 3 sociedades científicas implicadas en el tratamiento de las adicciones: SEPD, SOCIDROGALCOHOL y SOMAPA.

[Introduction] About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive)., [Methods and analysis] Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm)., [Ethics and dissemination] The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions., [Trial registration number] NCT04357860.

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at hig

[Background] Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). [Methods] In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication—hepatic decompensation or hepatocellular carcinoma (HCC)—or requiring liver transplant after SVR. [Results] During a median (Q1–Q3) follow-up of 31.6 (22.7–36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28–9.12]), pretreatment CPT class B or C (62.5 [3.08–1246.42]) and MELD scores (1.37 [1.03–1.82]), CPT class B or C at SVR (10.71 [1.32–87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49–13.15]), FIB-4 index at SVR (1.39 [1.13–1.70]), and LS at SVR (1.05 [1.02–1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. [Conclusions] LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

[EN] The continuous increase in our knowledge of HIV medicine and antiretroviral treatment has led us to draft specific consensus documents focused on topics other than antiretroviral therapy, such as treatment of opportunistic diseases, pre- and post-exposure prophylaxis, metabolic abnormalities, treatment of HBV or HCV coinfection, treatment of patients coinfected with tuberculosis, osteoporosis, kidney disorders, and cardiovascular risk. Accordingly, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology has promoted the drafting of this consensus document on the control and monitoring of adult patients infected with HIV. The document provides recommendations on the initial evaluation and subsequent monitoring of HIV-infected patients that will prove useful for all professionals involved in the management of this infection., [ES] La complejidad creciente de los conocimientos relativos a la infección por el VIH y al tratamiento antirretroviral (TAR) ha condicionado la elaboración de documentos de consenso específicos que abordan aspectos diferentes al TAR. Son ejemplos, la profilaxis y el tratamiento de las infecciones oportunistas, la profilaxis post y pre-exposición, las alteraciones metabólicas y el riesgo cardiovascular, la osteoporosis, los trastornos renales, la co-infección por el VHB y el VHC o el manejo de este en pacientes con tuberculosis, entre otros. En esta línea, la Junta Directiva de GeSIDA ha promovido la elaboración de un documento de consenso sobre el control y la monitorización de los adultos infectados por el VIH. El objetivo de este documento es proporcionar una serie de recomendaciones sobre la evaluación inicial y la posterior monitorización clínica de los pacientes infectados por el VIH, que pueda servir como referencia para todos los profesionales implicados en el cuidado de estos pacientes.

Among patients with cirrhosis, recovery of liver function after SVR to all‐oral direct‐acting antivirals (DAA ) in HIV /HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV ‐monoinfected and HIV /HCV ‐coinfected patients with cirrhosis who achieved SVR 12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR ‐DAA and GEHEP ‐MONO cohorts were selected if they had SVR 12 to all‐oral DAA s. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child‐Pugh‐Turcotte (CPT ) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR 12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR 12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV ‐infected individuals and in 82 (57%) HIV /HCV ‐coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV ‐monoinfected patients and in 33 (13%) HIV /HCV ‐coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR ) 2.1 (95% confidence interval, 95% CI : 1.03‐4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI : 1.004‐3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI : 1.2‐5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI : 3‐12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV ‐monoinfected and HIV /HCV ‐coinfected cirrhotics. Gender, INR , bilirubin, and albumin levels were associated with liver function changes after response to DAA s.

[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.

Due to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17–1.75] relative-units [ru] versus 1.71 [1.00–2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA.

[Objectives] To assess the impact of all-oral direct-acting antiviral agent (DAA) regimens on the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients with cirrhosis., [Methods] This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence., [Results] The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27–84) months, 22 (4.4%; 95% CI 2.6–6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06–1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14–0.85) per 100 PY whereas it was 1.79 (1.11–2.88) per 100 PY in the remaining cohort (P = 0.0005). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12–0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P = 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070–0.991; P = 0.049)., [Conclusions] SVR with all-oral DAA regimens reduces the risk of HCC in HIV/HCV-coinfected patients with compensated cirrhosis.

[Background] A liver stiffness below 21 kPa has a high negative predictive value to exclude the presence of esophageal varices at risk of bleeding in HIV/hepatitis C virus (HCV)-coinfected patients. Consequently, upper gastrointestinal endoscopy (UGE) for the screening of esophageal varices could be avoided in these patients. However, this strategy has not been widely accepted due to concerns about its safety., [Objective] To assess the ability of liver stiffness to predict the risk of portal hypertensive gastrointestinal bleeding (PHGB) in HIV/HCV-coinfected patients with compensated cirrhosis., [Methods] Prospective study of 446 HIV/HCV-coinfected patients with a new diagnosis of cirrhosis and no previous decompensation. All patients underwent a UGE for the screening of esophageal varices at entry in the cohort before November 2009. From this date, UGE was not recommended in patients with liver stiffness below 21 kPa. The time from diagnosis of cirrhosis to the emergence of PHGB was evaluated., [Results] After a median (quartile1–quartile3) follow-up of 49 (25–68) months, 15 (3.4%, 95% confidence interval 1.7–5%) patients developed a first PHGB episode. In all cases, baseline liver stiffness was at least 21 kPa. Thus, the negative predictive value of a liver stiffness below 21 kPa to predict PHGB during follow-up was 100%. At the time of the bleeding episode, liver stiffness was above this threshold in all patients., [Conclusions] Liver stiffness identifies HIV/HCV-coinfected patients with compensated cirrhosis with a very low risk of PHGB. In fact, no individual with liver stiffness below 21 kPa developed this outcome. Our results confirm that UGE can be safely spared in patients with liver stiffness below 21 kPa.

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12–3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23–6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01–11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.