Direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infection are endowed with sustained virological response (SVR) rates >95%. However, HCV cure does not completely eliminate the risk of hepatocellular carcinoma (HCC) development and liver decompensation. The present study investigated the impact of the administered DAA regimen on clinical long-time outcomes after SVR.Matched-pair survival analyses of 5802 chronically HCV infected patients from the German Hepatitis C-Registry compared the incidence of liver-related events 2.5 years after SVR in patients receiving either sofosbuvir (SOF)-based treatment or NS3/NS4A-protease inhibitor (PI)-containing DAA regimens. Hypothesis driven logistic regression analyses were performed to identify independent predictors for the occurrence of liver-related events.Matched-pair survival analyses revealed a borderline significant difference in the incidence of liver-related endpoints (except of HCC development) in patients receiving SOF-based treatment (4.1%) compared to PI-containing DAA regimens (2.6%) 2.5 years after SVR (p=0.061). Numerically, a trend towards a benefit of PI-based DAA treatment was observed (PI 65 events vs SOF 102 events). Hypothesis driven logistic regression analyses could not confirm SOF-based treatment as an independent predictor for the occurrence of liver-related events after HCV cure (p=0.072, OR=0.670).The incidence of liver-related events 2.5 years after HCV cure did not differ significantly between SOF-based DAA treatment and PI-containing regimens. However, numerically a trend towards a benefit of PI-based DAA treatment was observed. Therefore, a minor effect of the applied DAA regimen on the long-term incidence of liver-related events cannot be excluded.

Abstract Background & Aims With long-term consequences like the development of liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with a significant health burden. Information on HCV treatment outcomes and costs in routine care is still rare, especially for subgroups. The aim of this study was to analyse the treatment outcomes and costs of subgroups in routine care and to compare them over time with previous analyses. Methods Data were derived from a noninterventional study including a subset of 10298 patients receiving DAAs with genotypes 1 and 3. Sociodemographic, clinical parameters and costs were collected using a web-based data recording system. The total sample was subdivided according to treatment regimen, cirrhosis status as well as present HIV infection and opioid substitution treatment (OST). Results 95% of all patients achieved SVR. Currently used DAA showed higher SVR-rates and less adverse events (AE) compared to former treatments. Concerning subgroups, cirrhotic patients, HIV-coinfected patients and OST patients showed lower but still high SVR-rates. In comparison, cirrhotic had considerably longer treatment duration and more frequent (serious) AE. Overall, average treatment costs were €48470 and costs per SVR were €51129; for currently used DAAs costs amounted to €30330 and costs per SVR to €31692. After the end of treatment, physical health is similar to the general population in all patients except cirrhotic. Mental health remains far behind in all subgroups, even for currently used DAA. Conclusions Over time, some relevant factors developed positively (SVR-rates, costs, treatment duration, adverse events, health-related quality of life (HRQoL)). Further research on HRQoL, especially on mental health, is necessary to evaluate the differences between subgroups and HRQoL over time and to identify influencing factors.

Purpose of review The aim of this study was to highlight the profound changes in the cause in chronic liver disease in HIV-infected individuals. Recent findings Hepatitis C virus (HCV) has been transformed into a curable viral infection by highly effective treatments. This has resulted in elimination of chronic hepatitis C in HIV-coinfected individuals at least in resource-rich settings. Hepatitis B virus (HBV) has become a chronic infection, which is easily controlled by long-term therapy with HBV polymerase inhibitors. As a result, nonalcoholic steatohepatitis (NASH) has gained clinical importance. The obesity epidemic in the general population has also included people with HIV and weight gain has been associated with some newer antiretroviral drugs, such as HIV integrase inhibitors and tenofovir alafenamide fumarate. Medical treatment for obesity is a focus of intense research efforts, but currently, the only convincing therapeutic option in morbidly obese patients is bariatric surgery, which can also improve liver outcomes. The wider use of this approach has included HIV-infected individuals allowing to assess at least the safety aspects of bariatric surgery in this special population. Summary The shift from communicable to noncommunicable liver disease is changing the clinical practice in HIV-infected individuals. Research activities are focusing more on treatment of NASH and obesity, although a curative therapy for HBV infection would have a great clinical impact.

Zusammenfassung Einleitung Der Hepatitis C Genotyp 1 ist der häufigste Genotyp in West- und Zentraleuropa. In dieser Arbeit werden die Veränderungen der Baselinecharakteristika von 17 093 HCV-Patienten mit Genotyp 1a/1b, die im Zeitraum 2004–2018 in Deutschland antiviral therapiert wurden, analysiert. Es wurden insgesamt 5 Zeiträume betrachtet: (i) 2004–2007, (ii) 2008–2010, (iii) 2010–2013, (iv) 2014–2016, (v) 2017–2018. Methoden Die vorliegende Analyse basiert auf 5 deutschlandweit durchgeführten nicht-interventionellen Registern und umfasst Daten von Patienten, die mit dem HCV-GT1a und HCV-GT1b infiziert waren und zwischen 2004 und 2018 dokumentiert wurden [ML17071, ML19464, ML21645, ML25724 (Peginterferon alfa-2a® non-interventional study (PAN)) und dem Deutschen Hepatitis-C-Register (DHC-R)]. Ergebnisse Im Untersuchungszeitraum (2004–2018) hatten 7662 Patienten eine HCV-GT1a- und 9431 Patienten eine HCV-GT-1b-Infektion. GT1a-Patienten waren im Vergleich zu GT1b-Patienten jünger (46,5 Jahre vs. 51,2 Jahre) und häufiger männlich (70 % vs. 52 %). Drogenkonsum in der Vorgeschichte oder derzeit war im Untersuchungszeitraum häufiger bei GT1a-Patienten mit höchster Frequenz im aktuellsten Zeitraum (2017–2018; 44 % GT1a, 10 % GT1b). Metabolische Komorbiditäten wie Übergewicht und Diabetes mellitus waren häufiger bei mit GT1b infizierten Frauen. Der Anteil des Genotyps 1a nahm von 34 % (Zeitraum 2004–2007) auf ca. 50 % (Zeitraum 2017–2018) relevant zu. 2004–2018 zeigte sich ein relevanter Wechsel des GT1a/1b-Quotienten bei Männern (2004–2007: 38 %/63 %; 2017–2018: 59 %/41 %) bei weitgehend konstantem GT1a-Anteil der Frauen von ca. 30 % deutschlandweit über alle 5 untersuchten Zeiträume.Der Anteil der weiblichen Patienten mit GT1a in der Region Ost war im Vergleich zu den anderen 3 Regionen über nahezu alle Zeiträume niedriger, am deutlichsten ausgeprägt 2004–2007: 14 % GT1a vs. 86 % GT1b. Zusammenfassung Im untersuchten Zeitraum (2004–2018) zeigte sich ein relevanter Anstieg der Genotyp-1a-Infektion bei Männern, nicht bei Frauen, assoziiert mit Drogenkonsum. Die Daten zeigen eine grundlegende Änderung in der HCV-Epidemiologie in Deutschland an, die Konsequenzen für das Therapiemanagement und die allgemeine Versorgung der Hepatitis-C-Patienten haben.

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BACKGROUND:Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting.PATIENTS AND METHODS:An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens.RESULTS:Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin.CONCLUSION:Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.

BACKGROUND & AIMS:AASLD/IDSA treatment guidelines for hepatitis C virus (HCV) infection state that testing for quantitative HCV RNA can be considered at the end of antiviral treatment (EOT) with interferon-free regimens. However, it remains unclear how to respond to a detectable or even quantifiable HCV RNA result. The aim of this study was to analyse the frequency and predictive value of detectable and quantifiable HCV RNA results at the EOT in patients with HCV genotype 1 infection treated with ledipasvir (LDV) and sofosbuvir (SOF) ± ribavirin (RBV) in a large real-world cohort. METHODS:A retrospective analysis of the DHC-R (Deutsches Hepatitis C-Register, German Hepatitis C-Registry) cohort was performed including all patients who were treated with LDV/SOF ± RBV and in whom HCV RNA testing was done with either the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) or the Abbott RealTime HCV assay (ART). RESULTS:The frequency of detectable HCV RNA at the EOT was 7% in this real-world study involving 471 patients. Furthermore, 3% of the patients (n = 14/471) even had quantifiable viral load at the EOT. Detectable and quantifiable results were more frequent if the ART was used for testing. However, SVR was achieved by 32/33 patients (97%) with detectable and even by all 14 patients (100%) with quantifiable HCV RNA results at the EOT. CONCLUSION:Detectable and even quantifiable HCV RNA results are quite frequent if highly sensitive HCV RNA assays are used. However, treatment prolongation is not indicated, as SVR rates remain high in these patients.

With the aging of the hepatitis C virus (HCV)-infected patient cohort and the availability of highly effective and tolerable treatment regimens, an increasing number of elderly patients are now eligible for HCV therapy. This study investigated clinical and epidemiologic characteristics of elderly HCV-infected patients as well as the effectiveness and safety of available therapies.

Treatment decisions are based on extent of fibrosis in patients with chronic hepatitis C (HCV) infection. Noninvasive diagnostic tools may help to avoid liver biopsy. We investigated the diagnostic accuracy of noncommercial serum scores in comparison with transient elastography (TE). Data analysis was undertaken based on 2458 patients enrolled in the German Hepatitis C Registry, in a prospective, observational study. Aspartate aminotransferase-to-platelet ratio index (APRI), FORNS index and FIB-4 score were calculated and the diagnostic accuracy was compared to TE. As estimated by TE, 955 (38.9%) patients had absence of significant fibrosis (SF), 736 (29.9%) patients had SF, and 767 (31.2%) patients were shown to have cirrhosis. Patients with absence of SF had a sustained virological response (SVR) rate of 97.9%, whereas SVR was attained in 96.2% and 92.2% in those with SF and cirrhosis, respectively (P < 0.0001). The area under the receiver operator characteristic curve (AUROC), sensitivity and specificity in discriminating of SF were 0.789, 0.596 and 0.939 by APRI; 0.838, 0.852 and 0.748 by FORNS index; and 0.828, 0.658 and 0.946 by FIB-4 score. AUROCs for the prediction of cirrhosis, sensitivity and specificity were 0.881, 0.851 and 0.854 by APRI; 0.846, 0.948 and 0.628 by FORNS index; and 0.907, 0.907 and 0.848 by FIB-4 score. In conclusion, in the present multicentre real-world cohort, SF and cirrhosis were predicted with high accuracy with noncommercial serum markers using TE as reference. Further prospective long-term follow-up is necessary to compare biomarkers with TE concerning liver-related outcome and overall mortality.

The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis C and sustained viral response: Role of the treatment regimen Graphical abstract Authors 1.The crude incidence of HCC occurrence for IFN-free patients is twice as high as for IFNcontaining patients 2. But IFN-free patients are more likely to be thrombocytopenic, treatment experienced, decompensated, and older 3. Once these differences are accounted for, the association between IFN-free therapy and HCC occurrence disappears 4 3 2 1 Incidence per 100 pys Crude incidence of HCC occurrence by regimen 1.26 2.53 IFNcontaining IFNfree 5 4 3 2 1 2.48 1.15 Hazard ratio Association between IFN-free vs. IFN-containing therapy and HCC occurrence Univariate analysis Multivariate analysis Characteristics IFNcontaining patients IFN-free patients Mean age % decompensated % treatment experienced % thrombocytopenic 48.1 yr 9.5 27.6 22.1 52.1 yr 30.4 52.2 39.3The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis and sustained viral response: role of the treatment regimen HighlightsCrude risk of HCC higher for IFN-free recipients than IFN-containing recipients.IFN-free and IFN-containing recipients differ with respect to confounding factors.Association between IFN-free therapy and HCC disappears after adjusting for baseline confounders.At HCC diagnosis, no differences in nodule size or nodule number were apparent by regimen.

Curative treatment of patients who previously failed hepatitis C virus (HCV) therapies is critical to achieving HCV elimination. Glecaprevir/pibrentasvir (G/P) demonstrated high rates of sustained virologic response at post-treatment week 12 (SVR12) in patients with HCV infection; however, retreatment of patients who failed G/P has yet to be evaluated. MAGELLAN-3 is an ongoing, open-label, phase IIIb trial evaluating the efficacy and safety of G/P plus sofosbuvir (SOF) plus ribavirin (RBV) as a retreatment regimen for patients who had virologic failure with G/P in an AbbVie study. Patients with HCV genotype (GT) 1, 2, 4, 5 or 6 infection, without cirrhosis, and naive to NS3/4A protease and NS5A inhibitors prior to virologic failure with G/P received 12 weeks of treatment; patients with GT3, and/or compensated cirrhosis, and/or experience with NS3/4A protease and NS5A inhibitors prior to virologic failure with G/P received 16 weeks of treatment. The primary efficacy endpoint was the SVR12 rate. Safety, tolerability, and presence of resistance-associated substitutions (RASs) were assessed. To date, 23 patients enrolled: 30% (7/23), 9% (2/23), and 61% (14/23) of patients had GT1, 2, and 3 infections, respectively; 30% (7/23) of patients had compensated cirrhosis, and 91% (21/23) had baseline RASs in NS5A. The SVR12 rate was 96% (22/23); 1 patient with GT1a infection and compensated cirrhosis had virologic failure. One unrelated serious adverse event (AE) of symptomatic cholelithiasis occurred. There were no treatment discontinuations. Retreatment of G/P virologic failures with G/P plus SOF plus RBV for 12 or 16 weeks was well-tolerated and highly efficacious, regardless of HCV genotype or baseline RASs.

Background & Aims: Ledipasvir/sofosbuvir (LDV/SOF) for 8 to 24 weeks is approved for the treatment of chronic hepatitis C virus infection (HCV). In the ION-3 study, 8 weeks of LDV/SOF was non-inferior to 12 weeks in previously untreated genotype 1 (GT1) patients without cirrhosis. According to the Summary of Product Characteristics (SmPC), 8-week treatment may be considered in naive non-cirrhotic GT1-patients. However, there are only limited data on the effectiveness of an 8-week regimen of LDV/SOF under real-world conditions. The aim of the present study was to characterise patients receiving 8 weeks of LDV/SOF compared to those receiving 12 weeks of LDV/SOF, and to describe therapeutic outcomes in routine clinical practice. Methods: The German Hepatitis C-Registry is a large national real-world cohort that analyses effectiveness and safety of antiviral therapies in chronic HCV. This data set is based on 2,404 patients. Treatment with SOF/LDV (without RBV) for 8 or 12 weeks was initiated on or before September 30, 2015. Results: Overall, 84.6% (2,034/2,404) of the safety population (intention-to-treat-1 [ITT1]) and 98.2% (2,029/2,066) of the per protocol (PP) population achieved sustained virological response at week 12 (SVR12). In the 8-week group, 85.1% (824/968) of ITT1 and 98.3% (821/835) of PP patients achieved SVR12, while in the 12-week group, 85.5% (1,210/1,415) of ITT1, and 98.1% (1,208/1,231) of PP patients achieved SVR12. When treated according to the SmPC, 98.7% (739/749) of the patients achieved SVR12 (PP). Relapse was observed in 9.5% (2/21) of cirrhotic patients treated for 8 weeks (PP). Conclusions: Under real-world conditions a high proportion of eligible patients receiving 8-week LDV/SOF treatment achieved SVR12. Relapse occurred more frequently in patients who did not meet the selection criteria according to the SmPC. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Background The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. Methods PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). Results SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. Conclusion The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.

We present two consensus definitions of advanced and late stage liver disease being used as epidemiological tools. These definitions can be applied to assess the morbidity caused by liver diseases in different health care systems. We focus is on hepatitis B and C virus infections, because effective and well tolerated treatments for both of these infections have greatly improved our ability to successfully treat and prevent advanced and late stage disease, especially if diagnosed early. A consensus definition of late presentation with viral hepatitis is important to create a homogenous, easy-to-use reference for public health authorities in Europe and elsewhere to better assess the clinical situation on a population basis.

Einleitung/Ziele: Eine Hepatitis C-Virusinfektion vom Genotyp 2 (HCV GT2) gilt allgemein als leicht behandelbar. Die Standardtherapie umfasst eine 12-wöchige Behandlung mit Sofosbuvir u. Ribavirin. Aufgrund geringer Patientenzahlen variieren die Ausheilungsraten verschiedener Studien erheblich. Andere Behandlungsstrategien für HCV GT2 wurden bislang nicht systematisch untersucht.