Does Genotype-Specific Phenotype in Patients with Multiple Endocrine Neoplasia Type 2 Occur as Current Guidelines Predict?

The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary hyperparathyroidism (PHPT) is related to the respective pathogenic variant of the RET proto-oncogene. The aim of this study is to retrospectively analyze the individual, genotype-dependent clinical manifestations of a large cohort of MEN2 patients. By comparing their clinical profile with currently existing evidence-based knowledge, an optimal therapy and prevention strategy in terms of prophylactic thyroidectomy and clinical follow-up could be ensured. This is a retrospective single-center study of 158 MEN2 patients who were diagnosed and/or surgically treated at a tertiary referral care center between 1990 and 2022. All participants were categorized according to their pathogenic variant of the RET proto-oncogene. Subsequently, the clinical manifestation of the disease and its time of occurrence was documented. Our analysis showed results in line with existing studies, except for a considerably lower-than-predicted occurrence of PCC in patients with V804M/L mutations. This study supports the current recommendation regarding the pathogenic variant-dependent management of this rare cancer-associated syndrome.

Feasibility of Autofluorescence Using Overlay Imaging for the Detection of Parathyroid Glands: Defining Standards.

BACKGROUND: The aim of this study is to define standards for the use of near-infrared autofluorescence (NIRAF)-based overlay imaging via EleVision IR (Medtronic, Dublin, Ireland) and to evaluate its clinical applicability. PATIENTS AND METHODS: This prospective study included 189 patients who had undergone open thyroid and/or parathyroid surgery and in whom EleVision IR was applied to visualize at least one parathyroid gland (PG) between January 2021 and May 2022 in a tertiary referral care center. Whether the PGs were first localized by the surgeon or by overlay imaging was noted. Handling of the device, application time and duration, distance, infrared intensity (IR%), and the angle of each measurement were analyzed. In thyroidectomies, the specimens were subsequently scanned for further PGs. NIRAF patterns and intensities were described. RESULTS: Overall, 543 PGs were analyzed in 158 (83.6%) surgeries of thyroid glands (TGs) and in 49 (25.9%) surgeries for hyperparathyroidism. In 111 (58.7%) patients, identical numbers of PGs were detected by the surgeon and by overlay imaging. While a larger number of PGs was identified by the surgeon in 48 (25.4%) patients, overlay imaging served to detect more PGs in 30 (15.9%) cases. In four (2.1%) patients, PGs were visualized post-thyroidectomy due to their autofluorescence on the specimen. NIRAF-based overlay imaging was applied to depict the PGs early on after exposure by the surgeon. The ideal distance for the measurement ranged between 8 and 12 cm with an angle of 90° and a mean IR% of 34.5% (± 17.6). CONCLUSIONS: Considering the standard operating procedures, NIRAF-based overlay imaging can be used as an adjunct tool for intraoperative localization.

Progress of Hepatitis C elimination in Viennese people living with HIV after two decades of increasing cure rates.

BACKGROUND & AIMS: 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). METHODS: Consecutive HIV/HCV-coinfected patients starting HCV treatment at the Vienna General Hospital between 2002 and 2020 were retrospectively enrolled. RESULTS: 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. CONCLUSIONS: 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.

HCV hotline facilitates Hepatitis C elimination during the COVID-19 pandemic.

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.

Response-guided long-term treatment of chronic hepatitis D patients with bulevirtide-results of a "real world" study.

BACKGROUND AND AIM: Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real-life data on BLV efficacy are limited. METHODS: Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV-RNA after 24 weeks were offered PEG-IFN as an add-on therapy in a response-guided manner. RESULTS: Twenty-three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV-RNA: 2.1 × 105 copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty-two completed ≥24 weeks of treatment (24-137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV-RNA undetectability, but both became HDV-RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG-IFN in eight patients induced an HDV-RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV-RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy. CONCLUSION: Long-term BLV monotherapy is safe and effectively decreases HDV-RNA and ALT-even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG-IFN remains to be established. An algorithm for a response-guided BLV treatment approach is proposed.

Gadoxetic acid-enhanced MRI-derived functional liver imaging score (FLIS) and spleen diameter predict outcomes in ACLD.

BACKGROUND & AIMS: Functional liver imaging score (FLIS) - derived from gadoxetic acid-enhanced MRI - correlates with liver function and independently predicts liver-related mortality in patients with chronic liver disease (CLD), while splenic craniocaudal diameter (SCCD) is a marker of portal hypertension. The aim of this study was to investigate the accuracy of a combination of FLIS and SCCD for predicting hepatic decompensation, acute-on-chronic liver failure (ACLF), and mortality in patients with advanced CLD (ACLD). METHODS: We included 397 patients with CLD who underwent gadoxetic acid-enhanced liver MRI. The FLIS was calculated by summing the points (0-2) of 3 hepatobiliary-phase features: hepatic enhancement, biliary excretion, and portal vein signal intensity. Patients were stratified into 3 groups according to liver fibrosis severity and presence/history of hepatic decompensation: non-ACLD, compensated ACLD (cACLD), and decompensated ACLD (dACLD). RESULTS: SCCD showed excellent intra- and inter-reader agreement. Importantly, SCCD was an independent risk factor for hepatic decompensation in patients with cACLD (per cm; adjusted hazard ratio [aHR] 1.13; 95% CI 1.04-1.23; p = 0.004). Patients with cACLD and a FLIS of 0-3 points and/or a SCCD of >13 cm were at increased risk of hepatic decompensation (aHR 3.07; 95% CI 1.43-6.59; p = 0.004). In patients with dACLD, a FLIS of 0-3 was independently associated with an increased risk of ACLF (aHR 2.81; 95% CI 1.16-6.84; p = 0.02), even after adjusting for other prognostic factors. Finally, a FLIS and SCCD-based algorithm was independently predictive of transplant-free mortality and stratified the probability of transplant-free survival (TFS) in ACLD (p <0.001): FLIS 4-6 and SCCD ≤13 cm (5-year TFS of 84%) vs. FLIS 4-6 and SCCD >13 cm (5-year TFS of 70%) vs. FLIS 0-3 (5-year TFS of 24%). CONCLUSION: The FLIS and SCCD are simple imaging markers that provide complementary information for risk stratification in patients with compensated and decompensated ACLD. LAY SUMMARY: Magnetic resonance imaging (MRI) can be used to assess the state of the liver. Previously the functional liver imaging score, which is based on MRI criteria, was developed as a measure of liver function and to predict the risk of liver-related complications or death. By combining this score with a measurement of spleen diameter, also using MRI, we generated an algorithm that could predict the risk of adverse liver-related outcomes in patients with advanced chronic liver disease.

Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension.

BACKGROUND & AIMS: Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. METHODS: Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. RESULTS: 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). CONCLUSION: Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.

The prognostic value of HVPG-response to non-selective beta-blockers in patients with NASH cirrhosis and varices.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis has become a leading cause of cirrhosis. The prognostic value of (HVPG)-guided NSBB prophylaxis remains to be investigated in the setting of NASH cirrhosis. METHODS: Patients with NASH cirrhosis and varices undergoing HVPG-guided NSBB therapy were included. HVPG-response to NSBBs was evaluated within a median 52 (IQR:28-71) days after baseline measurement. HVPG-Response was defined as a decrease of ≥10% from baseline or below <12 mmHg. The composite endpoint was defined as variceal bleeding, decompensation, and liver-related death. RESULTS: Thirtyeight patients were included: Child-A/B:33(87%), Child-C:5(13%) median HVPG:19.7 ± 4.7 mmHg. 21(55.3%) patients achieved HVPG-response to NSBB. Presence of diabetes(aOR:0.16, p = 0.038) and arterial blood pressure (aOR:1.07, p = 0.044) were independently associated with NSBB-response. While NSBB-HVPG-responders showed fewer decompensations within 90 days (n = 1(5%) vs. n = 3(29%), p = 0.172), only Child-Pugh stage B/C (p = 0.001), MELD ≥ 15(p = 0.021) and HVPG ≥ 20 mmHg(p = 0.011) predicted the composite endpoint at 90 days. Similarly, after 2years of follow-up, only Child-Pugh stage (B:p = 0.001, C:p < 0.001), MELD ≥ 15 (p = 0.021), HVPG≥20 mmHg (p = 0.011) predicted the composite endpoint. Importantly, all bleeding events occurred in HVPG-NSBB non-responders. CONCLUSION: HVPG-response to NSBB was achieved in 55.3% of NASH patients with varices and this seemed to protect from variceal bleeding. However, only baseline HVPG ≥ 20 mmHg, Child-Pugh stage B/C and MELD ≥ 15 were predictors of decompensation/death in patients with NASH cirrhosis and varices.

Hepatitis D virus (HDV) prevalence in Austria is low but causes considerable morbidity due to fast progression to cirrhosis.

BACKGROUND: Hepatitis D virus (HDV) coinfection aggravates the course of hepatitis B virus (HBV). The prevalence of HDV in Austria is unknown. OBJECTIVE: This national study aimed at (i) recording the prevalence of HDV-infection in Austria and (ii) characterizing the "active" HDV cohort in Austria. METHODS: A total of 10 hepatitis treatment centers in Austria participated in this multicenter study and retrospectively collected their HDV patients between Q1/2010 and Q4/2020. Positive anti-HDV and/or HDV-RNA-polymerase chain reaction (PCR) results were retrieved from local database queries. Disease severity was assessed by individual chart review. Viremic HDV patients with clinical visits in/after Q1/2019 were considered as the "active" HDV cohort. RESULTS: A total of 347 anti-HDV positive patients were identified. In 202 (58.2%) patients, HDV-RNA-PCR test was performed, and 126/202 (62.4%) had confirmed viremia. Hepatocellular carcinoma was diagnosed in 7 (5.6%) patients, 7 (5.6%) patients underwent liver transplantation, and 11 (8.7%) patients died during follow-up. The "active" Austrian HDV cohort included 74 (58.7%) patients: Evidence for advanced chronic liver disease (ACLD, i.e., histological F3/F4 fibrosis, liver stiffness ≥10 kPa, varices, or hepatic venous pressure gradient ≥6 mmHg) was detected in 38 (51.4%) patients, including 2 (5.3%) with decompensation (ascites/hepatic encephalopathy). About 37 (50.0%) patients of the "active" HDV cohort had previously received interferon treatment. Treatment with the sodium-taurocholate cotransporting polypeptide inhibitor bulevirtide was initiated in 20 (27.0%) patients. CONCLUSION: The number of confirmed HDV viremic cases in Austria is low (<1% of HBV patients) but potentially underestimated. Testing all HBV patients will increase the diagnostic yield. More than half of viremic HDV patients had ACLD. Improved HDV testing and workup strategies will facilitate access to novel antiviral therapies.

COVID-19-Related Downscaling of In-Hospital Liver Care Decreased Patient Satisfaction and Increased Liver-Related Mortality.

The coronavirus disease 2019 (COVID-19) pandemic necessitated down-scaling of in-hospital care to prohibit the spread of severe acute respiratory syndrome-coronavirus-2. We (1) assessed patient perceptions on quality of care by telesurvey (cohort 1) and written questionnaire (cohort 2), and (2) analyzed trends in elective and nonelective admissions before (December 2019 to February 2020) and during (March to May 2020) the COVID-19 pandemic in Austria. A total of 279 outpatients were recruited into cohort 1 and 138 patients into cohort 2. All admissions from December 2019 to May 2020 to the Division of Gastroenterology/Hepatology at the Vienna General Hospital were analyzed. A total of 32.6% (n = 91 of 279) of cohort 1 and 72.5% (n = 95 of 131) of cohort 2 had telemedical contact, whereas 59.5% (n = 166 of 279) and 68.2% (n = 90 of 132) had face-to-face visits. A total of 24.1% (n = 32 of 133) needed acute medical help during health care restrictions; however, 57.3% (n = 51 of 89) reported that contacting their physician during COVID-19 was difficult or impossible. Patient-reported satisfaction with treatment decreased significantly during restrictions in cohort 1 (visual analog scale [VAS] 0-10: 9.0 ± 1.6 to 8.6 ± 2.2; P < 0.001) and insignificantly in cohort 2 (VAS 0-10: 8.9 ± 1.6 to 8.7 ± 2.1; P = 0.182). Despite fewer hospital admissions during COVID-19, the proportion of nonelective admissions (+6.3%) and intensive care unit admissions (+6.7%) increased. Patients with cirrhosis with nonelective admissions during COVID-19 had significantly higher Model for End-Stage Liver Disease (MELD) (25.5 [14.2] vs. 17.0 [interquartile range: 8.8]; P = 0.003) and ΔMELD (difference from last MELD: 3.9 ± 6.3 vs. 8.7 ± 6.4; P = 0.008), required immediate intensive care more frequently (26.7% vs. 5.6%; P = 0.034), and had significantly increased 30-day liver-related mortality (30.0% vs. 8.3%; P = 0.028). Conclusion: The COVID-19 pandemic's effects on quality of liver care is evident from decreased patient satisfaction, hospitalization of sicker patients with advanced chronic liver disease, and increased liver-related mortality. Strategies for improved telemedical liver care and preemptive treatment of cirrhosis-related complications are needed to counteract the COVID-19-associated restrictions of in-hospital care.

Epidemiological trends of HBV and HDV coinfection among Viennese HIV+ patients.

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 naïve [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-naïve 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.

Safety of direct oral anticoagulants in patients with advanced liver disease.

BACKGROUND & AIMS: While direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited. METHODS: Liver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low-molecular-weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti-Xa peak levels and thrombomodulin-modified thrombin generation assays (TM-TGAs) were measured in a subgroup of 35/28 DOAC patients. RESULTS: Among patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child-Pugh-stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure-related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow-up of 10.5 (IQR: 4.0-27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS-B/C (at 12 months: 36.9% vs CPS-A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59-6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00-16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82-9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti-Xa peak levels were higher in patients with CPS-B/C (345 [95% CI: 169-395] vs CPS-A: 137 [95% CI: 96-248] ng/mL, P = .048) and were associated with lower TM-TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients. CONCLUSIONS: Anticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.

Outcomes of an HCV elimination program targeting the Viennese MSM population.

BACKGROUND AND AIMS: Recent reports suggest an increasing incidence of hepatitis C virus (HCV) infections among MSM (men-who-have-sex-with-men). Early treatment with direct-acting antivirals (DAAs) achieves high cure rates and prevents further HCV transmission. We offered barrier-free HCV screening in the Viennese MSM population and immediate access to DAA treatment. METHODS: In collaboration with gay health specialists, we screened for HCV seropositivity in Viennese MSM between 2019 and 2020. Barrier-free HCV-RNA-PCR tests, transient elastography (TE) and immediate access to DAA treatment were offered. RESULTS: A total of 310 HCV-seropositive patients were identified. Of those, 145 could be contacted and 109 attended their appointment at our clinic. HIV-coinfection was highly prevalent in our cohort (n = 86/145; 78.9%), while pre-exposure prophylaxis (PrEP) was taken by 21.7% (n = 5/23) of non-HIV patients. Sexual risk behavior and (history of) intravenous drug use was reported by 32.1% and 13.8% of patients, respectively. Most MSM had already achieved sustained virological response (SVR) to previous antiviral treatment (n = 72, 66.1%) or experienced spontaneous clearance (n = 10, 9.2%). Advanced fibrosis was only detected in 3/109 (2.8%) patients. 30 MSM tested positive for HCV-RNA and DAA treatment was initiated in 29 patients - all achieved SVR. CONCLUSION: A targeted HCV test-and-treat program revealed a high prevalence of HCV seropositivity among Viennese MSM, potentially associated with high-risk sexual behavior and drug use. Early DAA treatment seems warranted in viremic HCV-MSM as SVR was 100%, which in turn prevents further HCV transmission.

Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR.

Genetic variants including PNPLA3-rs738409 C>G, TM6SF2-rs58542926 C>T, MBOAT7-rs641738 C>T, and HSD17B13-rs72613567 T>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.

Recent outbreaks of severe hepatitis A virus infections in Vienna.

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 < 0.001). Thirty-seven (53.6%) patients with severe HAV were hospitalized, 6 (9%) required ICU support, and one patient received liver transplantation within 30 days. Patients with severe HAV and liver dysfunction were more often male (60.5 vs. 43.1%, p = 0.055) and younger (31.5 vs. 63 years, p < 0.001) as compared with other HAV-IgM (+) cases. The observed increase of severe HAV infections in Vienna in 2017 among young males, coincided with a multinational HAV outbreak among MSM. Our data suggests a higher likelihood of severe courses of hepatitis A in MSM. Vaccination against HAV should be recommended for risk groups.

Noninvasive Risk Stratification After HCV Eradication in Patients With Advanced Chronic Liver Disease.

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 < 12.4 kPa and/or FU-VITRO < 0.95) to rule out clinically significant portal hypertension (CSPH, hepatic venous pressure gradient ≥10 mm Hg) at FU assigned most (57.3%) of the patients to the low-risk group; none of these patients developed hepatic decompensation. In contrast, in patients in whom FU-CSPH was ruled in (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.

Direct patient-physician communication via a hepatitis C hotline facilitates treatment initiation in patients with poor adherence.

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%.

MRI-defined sarcopenia predicts mortality in patients with chronic liver disease.

BACKGROUND & AIMS: To explore whether sarcopenia, diagnosed by an abbreviated magnetic resonance imaging (MRI) protocol is a risk factor for hepatic decompensation and mortality in patients with chronic liver disease (CLD). METHODS: In this retrospective single-centre study we included 265 patients (164 men, mean age 54 ± 16 years) with CLD who had undergone MRI of the liver between 2010 and 2015. Transverse psoas muscle thickness (TPMT) was measured on unenhanced and contrast-enhanced T1-weighted and T2-weighted axial images. Sarcopenia was defined by height-adjusted and gender-specific cut-offs in women as TPMT < 8 mm/m and in men as TPMT < 12 mm/m respectively. Patients were further stratified into three prognostic stages according to the absence of advanced fibrosis (FIB-4 < 1.45, non-advanced CLD), compensated-advanced CLD (cACLD) and decompensated-advanced CLD (dACLD). RESULTS: The inter-observer agreement for the TPMT measurements (κ = 0.98; 95% confidence interval [95% CI]:0.96-0.98), as well as the intra-observer agreement between the three image sequences (κ = 0.99; 95% CI: 0.99-1.00) were excellent. Sarcopenia was not predictive of first or further hepatic decompensation. In patients with cACLD and dACLD, sarcopenia was a risk factor for mortality (cACLD: hazard ratio (HR):3.13, 95% CI: 1.33-7.41, P = .009; dACLD:HR:2.45, 95% CI: 1.32-4.57, P = .005) on univariate analysis. After adjusting for the model of end-stage liver disease (MELD) score, albumin and evidence of clinical significant portal hypertension, sarcopenia (adjusted HR: 2.76, 95% CI: 1.02-7.42, P = .045) remained an independent risk factor for mortality in patients with cACLD. CONCLUSION: Sarcopenia can be easily evaluated by a short MRI exam without the need for contrast injection. Sarcopenia is a risk factor for mortality, especially in patients with cACLD.