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The benefits of direct-acting antivirals towards the elimination of hepatitis C virus (HCV) in people living with HIV are decreased when individuals are reinfected with HCV following treatment. We aimed to systematically review the existing evidence of HCV reinfection risk after treatment among people living with HIV, including people who inject drugs and men who have sex with men (MSM), and to identify the factors that explain heterogeneity in the incidence of HCV reinfection.For this systematic review and meta-analysis, we searched PubMed, Scopus, Web of Science, Cochrane, PsycINFO, and conference presentations from date of database inception to Jan 10, 2022, for clinical trials and cohort studies providing data that could be used to calculate the incidence of HCV reinfection following HCV treatment. Random-effect meta-analysis models were used to calculate rate estimates. Study-level factors contributing to heterogeneity of reinfection estimates were assessed using meta-regression. This study is registered with PROSPERO, CRD42019146973.41 studies, predominantly conducted in Europe, were included, with a total of 9024 participants. The incidence of reinfection was 3·76 cases per 100 person-years of follow-up (95% CI 2·80-5·05; IRisk of HCV reinfection following treatment in people living with HIV was highest among MSM and those with recent HCV infection. Continued scale-up of HCV treatment and ongoing HCV screening and treatment of infection in this patient population should reduce viraemic burden and risk of reinfection.None.

Since nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in the Western world, clinicians need reliable noninvasive tools for the identification of NAFLD-associated fibrosis. Limited evidence on the performance of the novel shear wave elastography technique Elast-PQ (EPQ) in NAFLD is available.In this prospective, European multinational study we assessed the diagnostic accuracy of EPQ using vibration-controlled transient elastography (VCTE) as a reference standard.Among 353 NAFLD patients, 332 (94.1%) fulfilled reliability criteria of VCTE and EPQ (defined by IQR/median ≤0.3; 41.3% female, mean age: 59 [IQR: 16.5], mean BMI: 29.0 (7.1)). 4/353 (1.1%) and 17/353 (4.8%) had unreliable VCTE and EPQ measurements, respectively. VCTE-based NAFLD fibrosis stages were F0/F1: 222(66.9%), F2: 41 (12.3%), F3: 30 (9.1%), F4: 39 (11.7%). We found a strong correlation (Pearson R=0.87; p0.0001) and concordance (Lin's concordance correlation coefficient =0.792) of EPQ with VCTE. EPQ was able to identify NAFLD-fibrosis risk with the following EPQ cutoffs: ≥6.5 kPa for significant fibrosis (≥F2) (≥1.47 m/s; sensitivity: 78%; specificity: 95%; AUROC: 0.94), ≥6.9 kPa for advanced fibrosis (≥F3) (≥1.52 m/s; sens.: 88%, spec.: 89%; AUROC: 0.949), and ≥10.4 kPa for cirrhosis (F4) (≥1.86 m/s; sens.: 87%; spec.: 94%; AUROC: 0.949).The point shear wave elastography technique EPQ shows excellent correlation to and concordance with VCTE. EPQ can reliably exclude NAFLD fibrosis6.0 kPa (1.41 m/s) and indicate a high risk of advanced fibrosis ≥10.4 kPa (≥1.86 m/s).Die nichtalkoholische Fettleber (NAFLD) ist mittlerweile die häufigste Lebererkrankung in der westlichen Welt. Daher besteht ein Bedarf an nichtinvasiven Methoden zur Einschätzung des Fibrose-Risikos bei NAFLD. Über die Aussagekraft der neue Scherwellen-Technologie Elast-PQ (EPQ) liegen nur wenige Daten vor.Diese prospektive, europäische multinationale Studie untersuchte die diagnostische Genauigkeit von EPQ bei NAFLD-PatientInnen im Vergleich zur Vibrations-kontrollierten transienten Elastografie (VCTE).Von 353 NAFLD-Patient*innen erfüllten 332 (94,1%) die Zuverlässigkeitskriterien für VCTE und EPQ (definiert als IQR/median ≤0,3). Die Studienpopulation war zu 41,3% weiblich, mit einem medianen Alter von 59 [IQR: 16,5] Jahren und einem medianen BMI von 29 [IQR: 7] kg/mDie Punkt-Scherwellen-Elastografie-Methode EPQ zeigt eine exzellente Korrektion und Konkordanz mit der VCTE. Bei NAFLD-Patient*innen wird durch EPQ6,0 kPa (1,41 m/s) eine signifikante Fibrose ausgeschlossen und durch EPQ ≥10,4 kPa (≥1,86 m/s) ein hohes Risiko für eine fortgeschrittene Fibrose angezeigt.

Interferon(IFN)-based hepatitis C virus (HCV) therapy has been replaced by direct-acting antivirals (DAAs). We assessed temporal trends in patient characteristics, transmission risks, treatment initiation, and cure rates in eras of IFN, restricted DAA-access, and unrestricted DAA-access in Viennese HCV/HIV-coinfected patients (HIV/HCV). Consecutive HIV/HCV-coinfected patients starting HCV treatment at the Vienna General Hospital between 2002 and 2020 were retrospectively enrolled. Of all N = 508 HIV/HCV, 78% (398/508) were male and the mean age was 41.8 ± 9.5 years. ‘People-who-inject-drugs’ (PWID) accounted for 61% (311/508), while 31% (156/508) were ‘men who have sex with men’ (MSM). In the IFN-era, restricted DAA-era and unrestricted DAA-era, N = 152, N = 129, and N = 227 HCV treatments were started and 49% (74/152), 95% (122/129), and 88% (200/227) achieved sustained virologic response, respectively. Treatment during the IFN-era was a strong predictor for virologic non-response (aOR 12.69; 6.93–23.24) and loss-to-follow-up (aOR 6.12; 2.99–12.54), while virologic non-response was less common in ‘MSM’ (aOR 0.28; 0.13–0.62). Ninety three percent (50/54) of the observed HCV reinfections occurred in the unrestricted DAA-era. A substantial increase in ‘MSM’ transmission was observed since 2010 with 66% (107/161) in the DAA-era versus 15% (49/330) prior to the DAA-era. HCV cure rates in Viennese HIV patients increased from 49% in the IFN-era to 88–95% in the DAA-era. MSM-related risk behaviour and reinfections became the key challenges towards HCV elimination in HIV-coinfected patients.

Summary Background/aims Non-alcoholic fatty liver disease (NAFLD) is frequent in people living with HIV (PLWH) and may be aggravated by metabolic comorbidities and antiretroviral therapy (ART)-associated adverse effects. Methods We retrospectively assessed epidemiological, clinical and laboratory parameters and ART regimens at HIV diagnosis (BL) and at last follow-up (FU) in 1458 PLWH without viral hepatitis coinfection attending our HIV clinic in 2014–2016. Fibrosis was non-invasively assessed by the NAFLD fibrosis score (NFS). Results The median age of subjects was 37.8 years, 77.4% were male and 67.2% on ART, median CD4+ count was 356.0 cells/µL. At BL, 503 (34.5%) and 20 (1.4%) PLWH had dyslipidemia and diabetes, respectively. According to the NFS 16 (1.3%) showed advanced fibrosis (NFS ≥ 0.676), among which 1 (6.3%) had diabetes, 7 (43.8%) had dyslipidemia, and 5 (31.3%) were on HIV-protease inhibitors (PI). In addition, 191(15.1%) had intermediate NFS results, while fibrosis was ruled out (NFS ≤ 1.455) in 1065 (83.7%) PLWH. After a median follow-up of 6.3 years, 590 (42.8%) had dyslipidemia and 61 (4.4%) had diabetes. Also, 21 (1.6%) showed advanced fibrosis, of which 10 (47.6%) had diabetes, 4 (19.0%) had dyslipidemia, and 9 (42.9%) were on PI-based ART, 223 (17.4%) had intermediate NFS results, while 1039 (81.0%) showed no fibrosis. Conclusion During FU, advanced NAFLD fibrosis occurred in 1.3–1.6% of PLWH. Dyslipidemia, diabetes, and PI-based ART were associated with advanced NAFLD fibrosis. Prospective investigations of NAFLD severity and risk factors in PLWH are warranted.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a typical type-2 inflammation involving T-helper type-2 cells and impairing quality of life due to nasal obstruction, discharge and reduced sense of smell. Recently, the anti-IL4Rα antibody dupilumab was approved for CRSwNP. While dermatologic side effects in patients treated with dupilumab for atopic dermatitis are frequently observed, there is limited knowledge about these effects in patients with CRSwNP. We aimed to investigate frequency and characteristics of dermatologic side effects following initiation of dupilumab treatment in a cohort of Austrian CRSwNP patients. Therefore, CRSwNP patients presenting at the Department of Otorhinolaryngology, Head and Neck Surgery at the Vienna General Hospital were retrospectively evaluated for newly developed skin eruptions while under dupilumab treatment. Incidence was calculated and details on clinical symptoms were collected. One hundred and ninety-two CRSwNP patients receiving dupilumab treatment were included, comprising a cumulative follow-up of 89.65 years (median: 5.5, IQR: 5.9). We observed dermatologic side effects in four patients starting at a median time of 15.5 (range 4-23) weeks after dupilumab initiation corresponding to an incidence-rate of 4.46 (95%-confidence interval 1.39-11.23) events per 100 patient-years follow-up. The majority (75%, 3/4) of affected patients developed psoriasis-like dermatitis, whereas one individual experienced rosacea-like folliculitis and alopecia areata. While dupilumab dosing was reduced in 3/4 CRSwNP patients, one patient completely stopped dupilumab therapy. Our study provides the first comprehensive evaluation of both frequency and characteristics of dermatologic side effects caused by dupilumab in CRSwNP patients. All affected patients developed Th1-inflammatory associated skin disorders - previously observed only in individuals with prior affections of the skin (i.e. atopic dermatitis). Thus, individuals receiving dupilumab for CRSwNP may develop novel symptoms that require interdisciplinary management. Future studies on dupilumab in a real-world setting will be required to further explore its spectrum of side effects.

Summary Background Hepatitis E virus (HEV) infection can cause severe viral hepatitis and eventually liver failure. We aim to provide novel data on the epidemiology and the course of HEV infections from Q1/2008 to Q3/2018 at the Vienna General Hospital. Methods Of the 88,945 people tested, we identified HEV-IgM positive (+) or HEV-PCR (+) patients and retrospectively collated information on the course of infection from patient records. Results Among 151 HEV-IgM or PCR (+) (median age 51 years, 45.8% female), 7 (4.6%) had non-severe acute HEV infection (ALT ≥ 2–5-fold upper limit of normal, ULN), 11 (7.3%) had severe HEV infection without liver dysfunction (LD) (ALT > 5-fold ULN), and 9 (6.0%) with LD (ikterus or bilirubin > 5 mg/dL, OR coagulopathy or INR > 1.5, OR encephalopathy or ammonia > 100 µmol/L). HEV-RNA-PCR was performed in 58/190 (30.5%) HEV-IgM (+) patients and was positive in 19 (30.6%). Rates of HEV IgM/PCR positivity remained stable over the observation period. The HEV genotype (GT) was GT‑1 in 71.4% (n = 5) and GT‑3 in 28.6% (n = 2). Travel history was recorded for 9/20 (45.0%) of severe HEV and 12/20 (60.0%) patients with severe HEV infection were hospitalized. One patient with pre-existing liver disease and concomitant EBV infection required intensive care. No patient required transplantation and the 30-day mortality was 3/151 (1.9%). Despite the increased testing rates, the absolute number of diagnosed HEV infections at Vienna General Hospital remained constant between 2008 to 2018. Conclusion Although approximately half of the patients with severe acute HEV infection required hospitalization, admissions to the intensive care unit (ICU) and short-term mortality were low.

The COVID-19 pandemic necessitates healthcare restrictions that also affected ongoing hepatitis C virus (HCV) elimination efforts. We assessed the value of a physician-operated HCV hotline on treatment and cure rates throughout the pandemic. All HCV patients undergoing HCV therapy at the Vienna General Hospital from 2019 to 2021 were included. An HCV hotline was established in 2019 and provided services including phone calls, text messages and voicemails. Patients were stratified by date of HCV therapy: 2019 (pre-COVID) vs. 2020/2021 (during-COVID) and use of the HCV hotline: users vs. non-users. Overall, 220 patients were included (pre-COVID: n = 91 vs. during-COVID: n = 129). The prevalence of intravenous drug use (60.5%) and alcohol abuse (24.8%) was high during COVID. During COVID, the number of DAA treatment starts declined by 24.2% (n = 69) in 2020 and by 34.1% (n = 60) in 2021 vs. pre-COVID (n = 91, 100%). Significantly more patients used the HCV hotline during-COVID (95.3%) vs. pre-COVID (65.9%; p .001). Sustained virologic response (SVR) was 84.6% pre-COVID and 86.0% during-COVID. HCV hotline users achieved higher SVR rates during-COVID (88.2% vs. 33.3%, p = .004), but also pre-COVID (96.7% vs. 61.3%, p .001) compared with non-users. Considering only patients with completed DAA treatments, SVR rates remained similarly high during-COVID (96.9%) versus pre-COVID (98.1%). HCV treatment initiations decreased during-COVID but importantly, nearly all DAA-treated HCV patients used the HCV hotline during the COVID pandemic. Overall, the SVR rate remained at 88.2% during COVID and was particularly high in HCV phone users-most likely due to facilitation of adherence.

Summary Background Despite the availability of effective and well-tolerated direct acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a substantial number of HCV patients remain untreated. Novel strategies targeting HCV patients with poor adherence are urgently needed to enable HCV elimination. Methods We implemented a physician-operated HCV hotline (HCV-Phone) that was promoted within the patient community and referral networks. Previously diagnosed HCV patients were contacted via the HCV-Phone and offered low-barrier access to DAA therapy. Patients/referring physicians could directly call or send messages to the HCV-Phone. The HCV-Phone related and unrelated visits as well as DAA treatment initiations throughout 2019 were documented. Patients were followed until October 2020. This study analyzed treatment initiation, adherence to scheduled visits and outcomes in patients in whom management was assisted by the HCV-Phone. Results Out of 98 patient contacts via the HCV-Phone 74 attended treatment assessment at our clinic. While 15 (20%) patients were HCV-RNA negative and 1 (1%) patient did not initiate therapy, 58 patients were recruited for DAA therapy via the HCV-Phone. A total of 21 additional patients who started DAAs without HCV-Phone assistance required the use of the HCV-Phone infrastructure later on during treatment, resulting in a total of 79 HCV-Phone related DAA therapies. The poor adherence of patients previously diagnosed with HCV at our clinic is underlined by the long duration from HCV diagnosis to DAA therapy of median 37.0 months (IQR 2.7–181.1 months). A total of 55 (70%) HCV patients achieved a sustained virological response (SVR), 5 (6%) discontinued therapy, 1 (1%) had a reinfection, while 10 (13%) and 8 (10%) patients were lost during DAA therapy or follow-up, respectively. Conclusion The implementation of a physician-operated phone hotline for patients with HCV infection facilitated treatment initiation in an HCV population with poor adherence. Mainly due to losses to follow-up, the SVR rate remained suboptimal with 70%.

International surveillance data show a constant rise in the number of Neisseria gonorrhoeae infections and an increase in drug resistance of N. gonorrhoeae. As recent N. gonorrhoeae surveillance data in Austria are scarce, this study investigated phenotypic and genotypic antimicrobial resistance in N. gonorrhoeae isolates.In total, 440 N. gonorrhoeae samples were collected at the Medical University of Vienna, and the minimal inhibitory concentrations (MICs) for a range of different antibiotics were determined. Sampling sites and treatments were recorded, and whole-genome sequencing of N. gonorrhoeae isolates was performed using allele libraries to determine genotypic resistance.The median MICs for ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline and penicillin were0.002 µg/mL,0.016 µg/mL, 0.25 µg/mL, 2.0 µg/mL, 1.5 µg/mL and 0.25 µg/mL, respectively. Annual comparison showed that MICs were generally stable for all antimicrobial agents except azithromycin, for which an increase in median MIC was observed from 2017 (0.25 µg/mL). There was no genetic resistance to ceftriaxone; 8% of samples displayed resistance mutations against cefixime, primarily located in the penA gene. Resistance to azithromycin increased from 2% in 2013 to 12% in 2020. MtrD mosaic had the highest impact on azithromycin susceptibility; 47% of the resistant isolates showed this mutation. The majority of cases of gonorrhoea were treated successfully with either ceftriaxone or a ceftriaxone/azithromycin regime. Two treatment failures occurred under monotherapy with doxycycline. Overall, genotypic resistance corresponded significantly to all respective MICs.The resistance rate of N. gonorrhoeae to antibiotics has remained stable in Vienna over the last decade, except for azithromycin. The strong correlation found between genetic and phenotypic patterns in this study holds promise for future diagnostics of N. gonorrhoeae resistance based on genotypes.

The recently reported epidemic of acute hepatitis C virus (HCV) infections -observed predominantly among men who have sex with men (MSM)-may now decline due to wide availability of direct-acting antivirals (DAAs). This study aimed to investigate the current trends of acute hepatitis C in Vienna. Patients presenting with acute hepatitis C between 01/2007 and12/2020 at the Vienna General Hospital were retrospectively enrolled and followed after virologic clearance/eradication. The introduction of unrestricted DAA access after 09/17 defined the 'DAA era', as compared to the 'pre-DAA era' prior to 09/17. We identified 134 acute hepatitis C cases in 119 patients with a mean age of 39 ± 9 years at inclusion. The majority of patients were male (92%), HIV-positive (88%) and MSM (85%). In the DAA era, a history of prior chronic HCV infection at inclusion was found in 24% (11/46) compared to 7% (5/73) in the pre-DAA era (p = .012). The annual rate of acute hepatitis C cases increased in the DAA era (17.11 per year) compared to the pre-DAA era (7.76 per year). The DAA era included an AHC-genotype-2 cluster and more HIV-negative acute hepatitis C cases (0% (0/73) vs. 30% (14/46), p .001). Patients were followed after spontaneous clearance or sustained virologic treatment response (SVR) for a total of 251.88 patient-years (median 1.39 years per patient). In the DAA era, we recorded 15 acute hepatitis C-reinfections - corresponding to an incidence rate of 5.96 (95% CI: 3.57-9.66) reinfections per 100-patient-years. We continue to observe a high incidence of acute hepatitis C in Vienna in the DAA era-primarily among HIV-positive MSM, but increasingly also in HIV-negative MSM.

BACKGROUND AND AIMS Despite vaccination recommendations, hepatitis B (HBV) and D (HDV) coinfections are common in HIV+individuals. METHODS HBV immunization status (anti-HBs) as well as HBV (HBsAg/HBV-DNA) and HDV (anti-HDV) coinfection rates were assessed in 1870 HIV+individuals at HIV diagnosis (baseline, BL) and last follow-up (FU). RESULTS Sixty-eight (3.6%) HIV patients were never tested for HBV. At BL, 89/1802 (4.9%) HIV patients were HBV coinfected. Four hundred and fifteen (23.0%) showed virological HBV clearance [HBsAg(-)/anti-HBc(+)/anti-HBs(+)] and 210 (11.7%) presented with anti-HBc(+) only. Seven hundred and ten (39.4%) were HBV naive [HBsAg(-)/anti-HBs(-)/anti-HBc(-)/HBV-DNA(-)], but only 378 (21.0%) received vaccinations with detectable anti-HBs(+) titres. Among the 89 HBV/HIV-coinfected patients, only 52 (58.4%) were tested for HDV: 11/49 (22.4%) had anti-HDV(+) and 3/12 (25.0%) showed HDV-RNA viraemia. During a median FU of 6.5 (IQR 7.2) years, 44 (4.6%) of the 953 retested BL HBV-negative patients acquired new HBV infection (including 15/304, 4.9% of vaccinated patients). Of the 89 patients, 22 (24.7%) patients cleared their HBsAg, resulting in 60/1625 (3.7%) HIV/HBV individuals at FU: 34 (56.7%) showed HBV-DNA suppression and 15 (25.0%) were HBV viraemic, while 12/89 (13.5%) remained without a FU test. Vaccinations induced anti-HBs(+) in 137 of the retested 649 (21.1%) BL HBV-naive patients. CONCLUSION HBV testing is well established among Viennese HIV+patients with HBV coinfection rates around 4%-5%. HBV vaccinations are insufficiently implemented since anti-HBs titres were detected in only 21.1% of HBV-naive HIV(+) patients and new HBV infections occurred in previously vaccinated patients. HDV testing is not systematically performed despite up to 25% of HIV/HBV patients may show HDV coinfection.

BackgroundIncreasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex practices and associated drug use remain poorly understood.MethodsForty-seven patients with HCV were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was excluded by guaiac paper test. Risk behavior was assessed by standardized questionnaires.ResultsMedian age was 41.9 years, 89% were HIV positive (+) (42/47) and 85% (40/47) were male, 58% (23/40) of whom were MSM. Acute HCV infection was diagnosed in 32% (15/47) ,with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had ≥1 HCV+ swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal), and contamination with blood was excluded in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 [IQR, 0.85] log IU/mL vs 4.08 [2.45] log IU/mL; P < .001). Using ROC-curve analysis, serum HCV-RNA cutoffs for ruling in/out any HCV+SS were established at 6.02 log IU/mL and 4.02 log IU/mL, respectively.ConclusionsHCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex practices and sharing of nasal drug-sniffing “tools” might be important HCV transmission routes, especially in patients with high serum HCV-RNA.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is defined as an ascitic polymorphonuclear cell count (A-PMN) > 250 cells/µl. OBJECTIVE: We aimed to investigate the prognostic value of ascitic fluid cell counts in patients without SBP. PATIENTS AND METHODS: A total of 178 patients were included and stratified by ascitic cell counts at index paracentesis: A-LEUK-low (500/µl) for leukocytes; A-PMN-low (250/µl) for PMN cells. RESULTS: One-year mortality was comparable between group A-LEUK-SBP (53.9%) and patients with subclinical cell counts (34.5% for A-LEUK-low, 43.5% for A-LEUK-intermediate, log-rank p = 0.547). However, we observed an increase in one-year mortality already in group A-PMN-intermediate with 75% and A-PMN-SBP with 80.9% (vs 40.5% for A-PMN-low, log-rank p = 0.016). Importantly, increases of A-PMN cell counts between two paracenteses were associated with increased mortality: per 100 cells/µl increase of absolute A-PMN cell count: hazard ratio (HR): 1.03 (95% confidence interval (CI): 1.01–1.06), p = 0.005; per 5% increase of relative PMN cell count: HR: 1.15 (95% CI: 1.06–1.26), p = 0.001. CONCLUSION: Patients with PMN cell counts of 125–250/µl are at high risk for mortality, which was very similar to SBP patients with PMN cell counts >250/µl. This highlights the need for preventive strategies. The prognostic value of changes in relative ascitic PMN cell counts should be evaluated in future studies.

BACKGROUND: The treatment of acute hepatitis C (AHC) with direct-acting antiviral agents (DAAs) is considered a cornerstone of hepatitis C virus (HCV) elimination strategies, especially in human immunodeficiency virus (HIV)-infected individuals at high risk of onward transmission. OBJECTIVE: Optimal treatment regimens and duration for AHC in HIV-coinfected patients remain to be established. Thus, we aimed to evaluate the efficacy and safety of DAA treatment regimens in the setting of AHC. METHODS: All HIV-positive patients with a diagnosis of AHC according to the European AIDS Treatment Network (NEAT) consensus attending our clinic after 2014 were included. DAA treatment regimens and duration were based on current recommendations for chronic hepatitis C (CHC) at treatment initiation. RESULTS: Thirty-eight HIV/AHC patients (median age 42.0 years), mostly men who have sex with men (92%), were started on interferon-free regimens. HCV-genotype (GT) was predominately GT-1a (65%). The following DAA regimens were prescribed: ombitasvir/paritaprevir/ritonavir/dasabuvir (42%; 16/38), glecaprevir/pibrentasvir (29%; 11/38), sofosbuvir/ledipasvir (13%; 5/38), ombitasvir/paritaprevir/ritonavir (5%; 2/38), grazoprevir/elbasvir (5%; 2/38) and sofosbuvir/velpatasvir (5%; 2/38). All HIV/AHC patients achieved sustained virologic response 12 weeks after end of treatment (SVR12) (100%; 38/38). DAA-related adverse events were rare. CONCLUSION: Interferon-free DAA regimens (including 34% pan-genotypic regimens) yielded 100% SVR12 in HIV/AHC individuals if treatment durations similar to CHC are applied.

Genetic variants including PNPLA3-rs738409 C&gt, G, TM6SF2-rs58542926 C&gt, T, MBOAT7-rs641738 C&gt, T, and HSD17B13-rs72613567 T&gt, TA have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e., changes in hepatic venous pressure gradient [HVPG] and non-invasive surrogates [liver stiffness measurement (LSM), von Willebrand factor (VWF), and VWF/platelet count ratio (VITRO)]) and clinical outcomes after CHC cure in 346 patients with pre-treatment ACLD. Patients carrying the PNPLA3 minor allele had more advanced liver disease prior to antiviral therapy, confirming its impact on liver disease progression. In a subgroup of 88 patients who underwent paired HVPG-measurements and were genotyped for all SNP/indels, PNPLA3/TM6SF2/MBOAT7/HSD17B13 genotypes were not associated with changes in HVPG. In line, changes in non-invasive surrogates of portal hypertension (LSM/VWF/VITRO) were comparable between carriers and non-carriers of the PNPLA3 G-allele in the overall cohort. Finally, carriage of PNPLA3 G-allele was not associated with the development of hepatic decompensation, de-novo hepatocellular carcinoma, or transplant-free mortality during a median follow-up of 42 months after the end of antiviral treatment. Therefore, genetic variants in PNPLA3/TM6SF2/MBOAT7/HSD17B13 do not impact the regression of portal hypertension and clinical outcomes in patients with pre-treatment ACLD after CHC cure.

Background and Aims Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of noninvasive surrogates of portal hypertension (liver stiffness measurement [LSM] by vibration‐controlled transient elastography and von Willebrand factor/platelet count ratio [VITRO]) for development of hepatic decompensation and hepatocellular carcinoma in patients with pretreatment advanced chronic liver disease (ACLD) who achieved HCV cure. Approach and Results A total of 276 patients with pretreatment ACLD and information on pretreatment and posttreatment follow‐up (FU)‐LSM and FU‐VITRO were followed for a median of 36.6 months after the end of interferon‐free therapy. FU‐LSM (area under the receiver operating characteristic curve [AUROC]: 0.875 [95% confidence interval [CI]: 0.796‐0.954]) and FU‐VITRO (AUROC: 0.925 [95% CI: 0.874‐0.977]) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU‐LSM 25.3 kPa and/or FU‐VITRO > 3.3; 25.0% of patients), the risk of hepatic decompensation at 3 years following treatment was high (17.4%). Patients within the diagnostic gray‐zone for FU‐CSPH (17.8% of patients) had a very low risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n = 86) and external (n = 162) cohort. Conclusion FU‐LSM/FU‐VITRO are strongly and independently predictive of posttreatment hepatic decompensation in HCV‐induced ACLD. An algorithm combining these noninvasive markers not only rules in or rules out FU‐CSPH, but also identifies populations at negligible versus high risk for hepatic decompensation. FU‐LSM/FU‐VITRO are readily accessible and enable risk stratification after sustained virological response, and thus facilitate personalized management.

To explore the epidemiology and clinical course of hepatitis A virus (HAV) infections at the Vienna General Hospital. We retrospectively identified patients who were tested positive for HAV-IgM at the Vienna General Hospital form Q1/2008 to Q3/2018. Our definition of severe HAV infection was AST and/or ALT > 5 × above the upper limit of normal (ULN); and liver dysfunction as (i) hepatic encephalopathy or ammonia > 100 μmol/L, (ii) coagulopathy with INR > 1.5, or (iii) jaundice with bilirubin > 5 mg/dL. A total of 578 HAV-IgM (+) were identified, including 31 (5.4%) and 38 (6.6%) without and with liver dysfunction, respectively. A proportional increase in severe HAV cases with and without liver dysfunction occurred in 2016/2017 with (21.5% (vs. 8.0% in the years before; p

Summary Background and aim Hepatitis C virus (HCV) therapy should be considered without delay in all patients with significant (SIGFIB) or advanced liver fibrosis (ADVFIB). We aimed to investigate the rates of treatment initiation with interferon-free regimens within a screening program for SIGFIB/ADVFIB in human immunodeficiency virus/HCV coinfected patients (HIV/HCV). Methods The FIB-4 was calculated in all HIV/HCV from 2014–2016. HIV/HCV were counselled by the HIV clinic and referred to the Division of Gastroenterology and Hepatology for transient elastography (TE) and evaluation for HCV therapy. Patients were stratified by FIB-4 of 7.1 kPa/>9.5 kPa, respectively. Results Among 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One hundred HIV/HCV had a FIB-4 ≥1.45. Among these, 57% (57/100) underwent TE. The majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57), however, interferon-free treatment was initiated in only 56% (24/43). In addition, fifty-two percent (57/110) of HIV/HCV with FIB-4

BaCKgRoUND aND aIMS: Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We as- sessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastogra- phy (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolu- tion of PH. appRoaCH aND ReSUltS: The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow-up [FU]) IFN-free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08- 1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninva- sive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC], < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86-0.92) in most patients, especially if assessed in a sequential manner. CoNClUSIoNS: Reassessment of HVPG after SVR im- proved prognostication in patients with pretreatment CSPH. An “immediate” HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for inter- ventions that lower portal pressure by decreasing intrahepatic resistance.

Human immunodeficiency virus (HIV)-induced metabolic abnormalities and antiretroviral therapy (ART), genetic factors, most importantly the rs738409 C G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene, as well as hepatitis C virus (HCV) coinfection may all cause hepatic steatosis (HS). However, recent studies suggest a protective effect of HCV infection on HS. Thus, we evaluated HS prior and after HCV eradication in an HIV/HCV-coinfected cohort at the Medical University of Vienna between January 2014 and June 2017. Two hundred forty-seven patients underwent liver stiffness measurement and controlled attenuation parameter (CAP)-based steatosis assessment. A subcohort of 138 patients also had follow-up CAP measurement after HCV eradication by direct-acting antivirals (DAAs). A CAP value ≥248 dB/m defined HS and all CAP values were adapted to compensate for body mass index (BMI) and diabetes mellitus. Among all 247 HIV/HCV-coinfected patients, HS was prevalent in 31%, mean age was 43.3 years, 75% were male, the main ethnicity was Caucasian (96%), and mean BMI was 23.33 kg/m

We aimed to investigate the impact of sustained virologic response (SVR) to interferon (IFN)-free therapies on portal hypertension in patients with paired hepatic venous pressure gradient (HVPG) measurements.One hundred and four patients with portal hypertension (HVPG ⩾6mmHg) who underwent HVPG and liver stiffness measurement before IFN-free therapy (baseline [BL]) were retrospectively studied. Among 100 patients who achieved SVR, 60 patients underwent HVPG and transient elastography (TE) after antiviral therapy (follow-up [FU]).SVR to IFN-free therapies significantly decreased HVPG across all BL HVPG strata: 6-9mmHg (BL: 7.37±0.28 vs. FU: 5.11±0.38mmHg; -2.26±0.42mmHg; p0.001), 10-15mmHg (BL: 12.2±0.4 vs. FU: 8.91±0.62mmHg; -3.29±0.59mmHg; p0.001) and ⩾16mmHg (BL: 19.4±0.73 vs. FU: 17.1±1.21mmHg; -2.3±0.89mmHg; p=0.018). In the subgroup of patients with BL HVPG of 6-9mmHg, HVPG normalized (6mmHg) in 63% (12/19) of patients, while no patient progressed to ⩾10mmHg. Among patients with BL HVPG ⩾10mmHg, a clinically relevant HVPG decrease ⩾10% was observed in 63% (26/41); 24% (10/41) had a FU HVPG10mmHg. Patients with Child-Pugh stage B were less likely to have a HVPG decrease (hazard ratio [HR]: 0.103; 95% confidence interval [CI]: 0.02-0.514; p=0.006), when compared to Child-Pugh A patients. In the subgroup of patients with BL CSPH, the relative change in liver stiffness (per %; HR: 0.972; 95% CI: 0.945-0.999; p=0.044) was a predictor of a HVPG decrease ⩾10%. The area under the receiver operating characteristic curve for the diagnosis of FU CSPH by FU liver stiffness was 0.931 (95% CI: 0.865-0.997).SVR to IFN-free therapies might ameliorate portal hypertension across all BL HVPG strata. However, changes in HVPG seemed to be more heterogeneous among patients with BL HVPG of ⩾16mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction. TE might be useful for the non-invasive evaluation of portal hypertension after SVR.We investigated the impact of curing hepatitis C using novel interferon-free treatments on portal hypertension, which drives the development of liver-related complications and mortality. Cure of hepatitis C decreased portal pressure, but a decrease was less likely among patients with more pronounced hepatic dysfunction. Transient elastography, which is commonly used for the non-invasive staging of liver disease, might identify patients without clinically significant portal hypertension after successful treatment.

Elastography point quantification (ElastPQ) is a new ultrasound-based shear wave elastography method for non-invasive assessment of liver fibrosis. We evaluated the diagnostic accuracy of ElastPQ in patients with chronic viral hepatitis. Fibrosis stage (F) was determined by transient elastography (F0/F1:7.1 kPa, F2: 7.1-9.4 kPa, F3: 9.5-12.4 kPa, F4: ≥12.5 kPa). Area under the receiver operator characteristics curve (AUROC) analysis was performed to assess ElastPQ cutoffs for significant fibrosis (≥F2) and cirrhosis (F4). Paired transient elastography and ElastPQ measurements were obtained from 217 patients (mean age ± SEM: 49 ± 0.79 years, 68.2% male, F0/F1: n = 98 [45.0%], F2: 47 [21.6%], F3: 22 [10.1%], F4: 50 [22.9%]). AUROC for ≥F2 was 0.843 (95% confidence interval: 0.791-0.895), and for F4, 0.933 (95% confidence interval: 0.894-0.972). The optimal ElastPQ cutoff for F2 was 6.68 kPa (sensitivity: 80.7%, specificity: 70.4%, positive predictive value: 78.5%, negative predictive value: 72.3%), and for F4 11.28 kPa (sensitivity: 86.0%, specificity: 85.6%, positive predictive value: 60.52%, negative predictive value: 97.16%). In conclusion, ElastPQ represents an accurate tool for non-invasive staging of liver fibrosis in patients with viral hepatitis.

We evaluated changes in relative liver enhancement (RLE) obtained by gadoxetic acid-enhanced MRI (GA-MRI) in the hepatobiliary phase and changes in splenic volume (SV) after hepatitis C virus (HCV) eradication as well as their predictive value for the development of (further) hepatic decompensation during follow-up. This retrospective study comprised 31 consecutive patients with HCV-induced advanced chronic liver disease who underwent GA-MRI before and after successful interferon-free treatment, as well as a cohort of 14 untreated chronic HCV-patients with paired GA-MRI. RLE increased by 66% (20%–94%; P<0.001) from pre- to posttreatment, while SV decreased by −16% (−28% to −8%; P<0.001). However, SV increased in 16% (5/31) of patients, the identical subjects who showed a decrease in RLE (GA-MRI-nonresponse). We observed an inverse correlation between the changes in RLE and SV (ρ=−0.608; P<0.001). In the untreated patients, there was a decrease in RLE by −11% (−25% to −3%; P=0.019) and an increase in SV by 23% (7%–43%; P=0.004) (both P<0.001 versus treated patients). Interestingly, GA-MRI-nonresponse was associated with a substantially increased risk of (further) hepatic decompensation 2 years after the end of treatment: 80% versus 8%; P<0.001. GA-MRI might distinguish between individuals at low and high risk of (further) hepatic decompensation (GA-MRI-nonresponse) after HCV eradication. This could allow for individualized surveillance strategies.