Background: Health and social outcomes of previous opiate users (POUs) are not well-documented. We characterize the life situation, health status, and health-related quality of life (HRQoL) of POUs entering antiviral hepatitis C (HCV) treatment, compared with HCV patients without past illicit opiate use (NOU), and with HCV patients currently in opiate agonist treatment (OAT). Methods: Data are taken from the German Hepatitis C-Registry (“Deutsches Hepatitis C-Register”, DHCR), a multi-centre registry study focussing on the course and outcome of HCV treatment with directly acting antivirals. At treatment entry, patients underwent a standardized clinical assessment, including the Short Form 36 (SF-36) for self-reported HRQoL. Results: POUs (n = 734) and OAT patients (n = 554) were similar with regard to age, sex, migrant background, and psychiatric comorbidity. Employment rate and cannabis, alcohol, and smoking abstinence rates were higher for POUs than for OAT patients, but still lower than for NOU (n = 4147) patients. Mental and physical HRQoL was better for POUs than for OAT patients, but worse than for NOU patients. Compared with SF-36 normative data, POUs showed decreased HRQoL, especially regarding mental health. Conclusions: Compared with opiate-dependent patients in OAT, POUs showed less psychotropic substance use and better HRQoL. Compared with NOU patients and the general population, mental health problems were especially increased. Challenges persist for POUs even during abstinence from opiates, highlighting the need for targeted interventions tailored to the specific needs of this population.

BACKGROUND:Previous exposure to hepatitis B virus (HBV) may influence the risk of developing hepatocellular carcinoma (HCC) and other liver-related events (LRE), in particular in patients after HCV cure. Previous studies were not conclusive and there are only few large studies on this topic from Europe. METHODS:We analysed clinical endpoints (≥ 3-point increase in MELD score, oesophageal variceal bleeding, ascites, encephalopathy, liver transplantation, death, with/without HCC; HCC alone) in patients cured from HCV. Data were obtained from the German Hepatitis C Registry. Patients after organ transplantation, a history of HCC, HIV co-infection, or HBsAg positivity were excluded. A subanalysis was conducted in patients with cirrhosis. Statistical analyses included logistic regression to identify predictors of clinical endpoints and Kaplan-Meier curves to analyse the influence of HBV serological markers. RESULTS:A cohort of 6198 patients fulfilled inclusion criteria, the median time of follow-up was 2.5 years (range 0.04-8.01). Serological evidence of previous HBV exposure was present in 1889 patients (anti-HBc positive). In patients with cirrhosis, univariate analyses identified anti-HBc positivity (odds ratio [OR], 1.48), cirrhosis (OR, 4.89), features of portal hypertension (ascites (OR, 5.66), oesophageal varices (OR, 4.88)), diabetes (OR, 3.23), and malignancies (OR, 10.34) as risk factors for composite LRE. In multivariable analysis, anti-HBc positivity (OR, 1.53) and cirrhosis (OR, 4.63) remained independent risk factors for the composite endpoints, whereas anti-HBc positivity was not associated with HCC or Kaplan-Meier survival analyses. CONCLUSIONS:Resolved HBV infection was not associated with the development of HCC or survival in Caucasians after HCV cure. Although anti-HBc positivity was linked to composite outcomes, its clinical relevance appears limited. TRIAL REGISTRATION:The registry was registered at the German Clinical Trials Register (DRKS; IDDRKS00009717).

Conclusion: Among patients with cirrhosis, the incidence of HCC decreases over time after HCV cure and is lowest in patients with younger age and compensated cirrhosis.The substantially lower incidence in F3 fibrosis is below the recommended threshold for costeffective screening.

While direct-acting antivirals (DAAs) cure chronic hepatitis C virus (HCV) infection in almost all patients, some patients remain at risk of liver disease despite HCV cure. In order to identify risk factors indicating liver-related morbidity and death after viral cure, we included 6982 patients from the national multicenter real-world German Hepatitis C Registry with regular follow-up visits for up to 7 years after DAA therapy. Definitions for normal liver function tests (in women/men) were alanine aminotransferase (ALT; ≤35/≤50 U/L), ALT according to American Association for the Study of Liver Diseases (AASLD; ≤19/≤30 U/L), and gamma-glutamyltransferase (GGT; ≤40/≤60 U/L). In our cohort, 97.4% of patients achieved sustained virologic response (SVR). At 24 weeks after SVR (SVR24), elevated ALT occurred in 657/6982 (9.4%), elevated ALT (AASLD) in 2609/6982 (37.4%), and elevated GGT in 1777/6982 (25.5%) patients. Risk factors for increased ALT at SVR24 were obesity, alcohol, cirrhosis, elevated baseline ALT, and non-SVR. Increased GGT at SVR24 was significantly (p < 0.05) and independently associated with male sex (odds ratio [OR], 2.12), higher body mass index (OR, 1.04), age >50 years (OR, 1.60), liver cirrhosis (OR, 3.97), alcohol consumption (OR, 2.99), diabetes (OR, 1.63), non-SVR (OR, 8.00), and elevated GGT at baseline (OR, 17.12). In multivariate regression analysis, elevated GGT at SVR24, particularly in combination with cirrhosis, was the best predictor for hepatic decompensation, hepatocellular carcinoma development, and death, followed by elevated ALT (AASLD) and standard ALT, which predicted hepatic decompensation. Despite successful HCV therapy, elevated GGT at SVR24 and to a lesser extent ALT are predictive of the future clinical outcome and linked with liver-associated comorbidities. This may highlight the relevance of nonalcoholic fatty liver disease, diabetes mellitus, alcohol, and cirrhosis for the clinical outcome in a vulnerable population, even after HCV cure.

BACKGROUND:Cytokine treatment with Interferon-alpha (IFN-α) represents a clinical model of immune associated depression, but it remains unclear if it is of the same entity as major depressive disorder (MDD). The study focuses on possible gender differences in IFN-α induced depression and effects of a pre-emptive antidepressant treatment. METHODS:Data from 181 patients with chronic hepatitis C infection (cHC) without history of mental illnesses undergoing treatment with IFN-α 2a and ribavirin were re-analyzed for gender effects. Patients with a pre-emptive antidepressant therapy with Escitalopram (n = 90, verum group) to prevent IFN-induced depression were compared to patients who received placebo (n = 91). Depressive symptoms before and during HCV-treatment were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale. RESULTS:We found significant differences regarding the incidence and severity of depressive symptoms between men and women for patients without antidepressant pre-treatment (placebo group). Significantly more women without pre-emptive antidepressant therapy suffered from clinically relevant depression (MADRS values ≥ 13, p = 0.041) and self-rated depressive symptoms (BDI ≥ 17, p = 0.024). Antidepressant pre-treatment showed comparable effects regarding the reduction of incidence and severity of depression in both women and men. CONCLUSIONS:Compared to MDD, IFN-alpha-induced depression in patients with cHC is also characterized by gender differences with an increased risk for women but no gender difference regarding the effects of an antidepressant pre-treatment is found. Our data strengthens the hypothesis that Interferon-induced depression serves as a clinical model for immune related depressive disorders.

Background and aims HCV-treated patients in opioid substitution treatment (OST) have shown persistently decreased health-related quality of life (HRQL). We characterize HRQL of OST and other patient groups after admission to HCV treatment. We also examine whether disease-related and psychosocial factors help explaining HRQL differences between patient groups.

Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (−0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48%, 31%, and 22% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated.

Improvement of health‐related quality of life (HRQoL) is frequently reported as a benefit when treating hepatitis C virus infection (HCV) with direct acting antivirals (DAA). As most of the available data were obtained from clinical trials, limited generalizability to the real‐world population might exist. This study aimed to investigate the impact of DAA therapy on changes in HRQoL in a real‐world setting. HRQoL of 1180 participants of the German Hepatitis C‐Registry was assessed by Short‐Form 36 (SF‐36) questionnaires. Scores at post‐treatment weeks 12–24 (FU12/24) were compared to baseline (BL). Changes of ≥2.5 in mental and physical component summary scores (MCS and PCS) were defined as a minimal clinical important difference (MCID). Potential predictors of HRQoL changes were analysed. Overall, a statistically significant increase in HRQoL after DAA therapy was observed, that was robust among various subgroups. However, roughly half of all patients failed to achieve a clinically important improvement in MCS and PCS. Low MCS ( p < .001, OR = 0.925) and PCS ( p < .001, OR = 0.899) BL levels were identified as predictors for achieving a clinically important improvement. In contrast, presence of fatigue ( p = .023, OR = 1.518), increased GPT levels ( p = .005, OR = 0.626) and RBV containing therapy regimens ( p = .001, OR = 1.692) were associated with a clinically important decline in HRQoL after DAA therapy. In conclusion, DAA treatment is associated with an overall increase of HRQoL in HCV‐infected patients. Nevertheless, roughly half of the patients fail to achieve a clinically important improvement. Especially patients with a low HRQoL seem to benefit most from the modern therapeutic options.

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.

Only limited data are available, regarding the influence of IFN-free, DAA-mediated therapy on patient reported outcomes (PROs) and clinical symptoms in patients with chronic hepatitis C infection. Therefore, we longitudinally assessed Short-Form 36 (SF-36) scores in HCV patients antivirally treated in a real world setting and focused on the identification of subgroups especially profiting from DAA regimens with respect to self-reported quality of life (QoL).

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.

In clinical trials and first real-life data, ombitasvir/paritaprevir/r ± dasabuvir ± ribavirin (RBV) has shown high rates of sustained virologic response (SVR) and good tolerability. Nevertheless, real-life data regarding the health-related quality of life (QoL) are limited. Here, we report the QoL in a large cohort from Germany that enrolled patients between December 2015 and December 2016.

Clinical trials and real-life data often focus on the safety and efficacy/effectiveness of ombitasvir/paritaprevir/r ± dasabuvir ± ribavirin (RBV). We conducted a large non-interventional observational study (LIFE-C) to assess effectiveness and safety, but also to learn more about key patient characteristics (i.e., comorbidities and co-medication) and the clinical management of prescribed co-medication in patients treated with ombitasvir/paritaprevir/r ± dasabuvir ± RBV in Germany.

Treatment of chronic hepatitis C genotype 3 (GT3) is more challenging compared with other genotypes. Since 2014, several new treatment regimens have been approved but sometimes based on limited data.