Zusammenfassung Hyperlipasämien treten häufig bei Lebererkrankungen auf. Alkoholkonsum, Diabetes und Medikamente können die Lipasekonzentration im Blut beeinflussen. Ziel dieser Registerstudie war es, den Effekt von direkt wirkenden antiviralen Arzneimitteln (DAAs) auf die Frequenz von Hyperlipasämien bei Patienten mit Hepatitis-C-Virus (HCV)-Infektion zu untersuchen. Weiterhin wurde Alkoholkonsum und die Diagnose eines Diabetes Mellitus als Einflussfaktor betrachtet.Lipasekonzentrationen von Patienten des Deutschen Hepatitis-C-Registers (2014–2022) wurden retrospektiv analysiert. Werte <60 U/l galten als normal. Hyperlipasämien wurden in „mild“, „moderat“ und „schwer“ eingeteilt. Patienten wurden anhand des Alkoholkonsums in „kein“, „niedriger“ und „hoher“ Alkoholkonsum oder dem Vorliegen eines Diabetes Mellitus kategorisiert.Vor DAA-Therapie zeigten 17,2% der Patienten erhöhte Lipasekonzentrationen. Posttherapeutisch sank die Frequenz an Hyperlipasämien, mit einem Tiefstwert von 12,1% in Jahr 6 nach Therapie. Patienten mit geringem Alkoholkonsum wiesen die niedrigste Hyperlipasämie-Rate auf. Diabetes war mit erhöhten Lipasekonzentrationen assoziiert. Schwere Hyperlipasämien traten gehäuft am Therapieende auf, waren jedoch insgesamt selten und klinisch inapparent. Fazit Hyperlipasämien sind bei HCV-Infektion häufig. Starker Alkoholkonsum und Diabetes sind zusätzliche Risikofaktoren für eine Hyperlipasämie. Ein Einfluss der DAA-Therapie auf die Prävalenz von Hyperlipasämien ist möglich. Weitere Einflussfaktoren einschließlich Lebensstil, Medikamenteneinnahme oder Organdysfunktionen müssen untersucht werden, um Kausalitäten herzustellen. Die Messung der Lipasekonzentration im Blut ohne spezifischen klinischen Grund muss kritisch hinterfragt und die Interpretation stets im Gesamtkontext betrachtet werden.

Abstract:Hyperlipasemia frequently occurs in liver diseases. Alcohol consumption, diabetes, and medications can influence blood lipase levels. The aim of this registry study was to investigate the effect of direct-acting antiviral agents (DAAs) on the frequency of hyperlipasemia in patients with hepatitis C virus (HCV) infection. In addition, alcohol consumption and the diagnosis of diabetes mellitus were considered as influencing factors.Lipase levels of patients from the German Hepatitis C Registry (2014-2022) were retrospectively analyzed. Values below 60 U/L were considered normal. Hyperlipasemia was categorized as "mild," "moderate," or "severe." Patients were grouped according to alcohol consumption ("none," "low," or "high") or the presence of diabetes mellitus.Before DAA therapy, 17.2 % of patients showed elevated lipase levels. After therapy, the frequency of hyperlipasemia decreased, reaching a minimum of 12.1 % in year 6 after treatment. Patients with low alcohol consumption showed the lowest rate of hyperlipasemia. Diabetes was associated with elevated lipase levels. Severe hyperlipasemia occurred more frequently at the end of therapy but was overall rare and clinically inapparent. CONCLUSION: Hyperlipasemia is common in HCV infection. Heavy alcohol consumption and diabetes are additional risk factors for hyperlipasemia. An effect of DAA therapy on the prevalence of hyperlipasemia is possible. Further influencing factors, including lifestyle, medication use, or organ dysfunction, need to be investigated to establish causality. Measurement of blood lipase levels without a specific clinical indication should be critically questioned, and results must always be interpreted within the overall clinical context.

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.

Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8%), and serious AEs in 44 patients (1.9%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination.

Objectives Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR) <30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population. Methods The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679). Results A total of 93 patients with GFR <30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR >30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%). Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir. Conclusion In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.

Background and aims Prevention, diagnosis and linkage to care are key factors to reach the goal of HCV elimination especially in vulnerable patient groups. A full course of direct acting antivirals (DAA) leads to HCV-cure in more than 90 % of patients chronically infected. Simplifying all aspects associated with DAA treatment may facilitate access in particular for vulnerable patient groups. To characterise patients who went lost-to-follow-up (LTFU) before end of treatment (EOT) might help to identify those in need for alternative access strategies to DAA therapy.

The number of patients diagnosed with hepatitis C virus (HCV) is markedly higher than the number initiating treatment indicating gaps in the care cascade, likely centred around reaching at-risk populations. Understanding changing characteristics of patients with HCV allows for targeted programs that increase linkage to care. We investigated changes in demographic and clinical characteristics of patients registered in the German Hepatitis C-Registry (DHC-R) from 1 January 2014 to 31 December 2019. The DHC-R is an ongoing, noninterventional, multicentre, prospective, observational cohort registry including 327 German centres. Patient characteristics were analysed over time in 7 phases for all patients completing a screening visit. Overall, 14,357 patients were enrolled. The percentage of treatment-naïve/non-cirrhotic patients increased from 34.4% in phase 1 (1 January-31 December 2014) to 68.2% in phase 7 (1 August-31 December 2019). The proportion of migrants, alcohol users, people who inject drugs, and those receiving opiate substitution therapy increased in later registry phases. Most patients (60.1%) were receiving comedication at baseline. The most prescribed comedications were drugs used to treat opioid dependence which increased from 9.2% in phase 1 to 24.0% in phase 7. The patients' mean age decreased from 52.3 years in phase 1 to 48.7 years in phase 7. From 2014 to 2019, the proportion of at-risk patients enrolling in the registry increased. To eliminate viral hepatitis as a major public health threat, a continued commitment to engaging underserved populations into the HCV care cascade is needed.

Background and aims Direct acting antivirals against hepatitis C improve the short-term outcome of patients with chronic hepatitis C. The long-term clinical course after interferon-free treatment of chronic hepatitis C has rarely been studied in large real-world cohorts. We here present data on 10,448 patients being followed for up to 7 years after DAA therapy in the German Hepatitis C-Registry.

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Einleitung Die HCV-Therapielandschaft hat sich seit Zulassung pan-genotypisch wirkender Kombinationstherapien signifikant verändert. Eine longitudinale Auswertung von Daten, die über den Zeitraum von 2015 bis 2020 erhoben wurden, zeigt trotz großer Fortschritte noch Potenzial für Verbesserungen der Patientenversorgung auf.

Despite the high effectiveness of direct-acting antivirals for the treatment of hepatitis C, a small proportion of patients do not respond to approved regimens. The combination regimen of SOF/VEL/VOX was recently approved for patients with failure to prior NS5A-based treatment. In this German real-world cohort including patients with cirrhosis ( 27.3 %) and previous decompensation events, 12 weeks of SOF/VEL/VOX resulted in high virologic response rates irrespective of disease severity and prior DAA regimen. Adverse events were mostly mild or moderate and comparable to those seen in the approval studies.

SummaryBackgroundGlecaprevir/pibrentasvir is a pangenotypic direct‐acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV). There are limited real‐world data on glecaprevir/pibrentasvir to date.AimTo evaluate the effectiveness and safety of glecaprevir/pibrentasvir under real‐world conditions in the German Hepatitis C‐Registry (DHC‐R).MethodsThe DHC‐R is an ongoing, non‐interventional, multicentre, prospective, observational cohort study that monitors patients with chronic HCV infection. Data were collected from patients who initiated glecaprevir/pibrentasvir and completed a screening visit on or after 2 August 2017. The primary effectiveness endpoint was sustained virological response at post‐treatment Week 12 (SVR12). Safety and tolerability were also assessed.ResultsAs of 15 July 2018, 586 patients received glecaprevir/pibrentasvir and had documented SVR12 data, treatment discontinuation, loss to follow‐up or HCV reinfection. Five hundred and fifty‐two patients (94%) received on‐label treatment. At baseline, most on‐label patients were infected with HCV genotype 1 (53%) or 3 (33%), HCV treatment‐naïve (90%), without cirrhosis (94%), and treated for 8 weeks (93%). Five hundred and thirty‐four patients (96.7%) achieved SVR12 (intention‐to‐treat [ITT] analysis). By modified ITT analysis (excluding patients who discontinued and did not achieve SVR12 or patients lost to follow‐up), the SVR12 rate was 99.4% (n/N = 534/537). There was one documented virological failure (relapse) and two documented HCV reinfections. One hundred and forty‐two (26%) adverse events (AEs) and 9 (2%) serious AEs occurred; 2 (<1%) AEs led to treatment discontinuation. All patients treated off‐label (N = 34) achieved SVR12.ConclusionGlecaprevir/pibrentasvir was highly effective and well tolerated under real‐world conditions. Clinical trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV). There are limited real-world data on glecaprevir/pibrentasvir to date. To evaluate the effectiveness and safety of glecaprevir/pibrentasvir under real-world conditions in the German Hepatitis C-Registry (DHC-R). The DHC-R is an ongoing, non-interventional, multicentre, prospective, observational cohort study that monitors patients with chronic HCV infection. Data were collected from patients who initiated glecaprevir/pibrentasvir and completed a screening visit on or after 2 August 2017. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Safety and tolerability were also assessed. As of 15 July 2018, 586 patients received glecaprevir/pibrentasvir and had documented SVR12 data, treatment discontinuation, loss to follow-up or HCV reinfection. Five hundred and fifty-two patients (94%) received on-label treatment. At baseline, most on-label patients were infected with HCV genotype 1 (53%) or 3 (33%), HCV treatment-naïve (90%), without cirrhosis (94%), and treated for 8 weeks (93%). Five hundred and thirty-four patients (96.7%) achieved SVR12 (intention-to-treat [ITT] analysis). By modified ITT analysis (excluding patients who discontinued and did not achieve SVR12 or patients lost to follow-up), the SVR12 rate was 99.4% (n/N = 534/537). There was one documented virological failure (relapse) and two documented HCV reinfections. One hundred and forty-two (26%) adverse events (AEs) and 9 (2%) serious AEs occurred; 2 (<1%) AEs led to treatment discontinuation. All patients treated off-label (N = 34) achieved SVR12. Glecaprevir/pibrentasvir was highly effective and well tolerated under real-world conditions. Clinical trial number: DRKS00009717 (German Clinical Trials Register, DRKS).