Structural Barriers In The Context Of Opiate Substitution Treatment In Germany - A Survey Among Physicians In Primary Care

Background Opiate substitution treatment (OST) is the most widely used treatment for opioid dependence in Germany with substantial long-term benefits for the patient and for society. Due to lessened restrictive admission criteria, the number of registered OST patients in Germany has increased continuously in the recent years, whereas the number of physicians providing OST has remained constant. Previous data already indicated a deteriorating situation in the availability or quality of OST delivered and that structural barriers impede physicians in actively providing OST. The present survey among a sample of primary care physicians in Germany aimed to identify and assess potential structural barriers for the provision of health care in the context of OST. Methods An anonymous written questionnaire was sent out to a sample of 2,332 physicians across Germany providing OST. Physicians contacted were identified through databases of the Federal State Chambers of Physicians and/or of the Federal Associations of Statutory Health Insurance Physicians. Data obtained were analysed descriptively. Results The response rate was 25,5% and the majority of 596 physicians sampled viewed substantial problems in terms of the regulatory framework of OST care in the German context. Furthermore, financial remuneration, insufficient qualification, as well as inadequate interdisciplinary cooperation in the treatment of comorbidities of opiate substituted patients were regarded as problematic. The number of physicians providing OST in Germany is expected to substantially decrease in the near future. Conclusion Despite less restrictive admission criteria for OST in Germany, the legal regulation framework for OST is still a limiting factor through raising concerns on the provider and consumer side to be unable to adhere to the strict rules. To avoid future shortages in the provision of OST care on the system level in Germany, revisions to the legal framework seem to be necessary. In regards to adequate care for drug use-related infectious diseases and psychiatric comorbidities commonly found in opiate substituted patients, efforts are required to improve professional qualifications of physicians providing OST as well as respective interdisciplinary collaboration

Irreversible impact of chronic hepatitis C virus infection on human natural killer cell diversity

Diversity is crucial for the immune system to efficiently combat infections. Natural killer (NK) cells are innate cytotoxic lymphocytes that contribute to the control of viral infections. NK cells were for long thought to be a homogeneous population of cells. However, recent work has instead revealed NK cells to represent a highly diverse population of immune cells where a vast number of subpopulations with distinct characteristics exist across tissues. However, the degree to which a chronic viral infection affects NK cell diversity remains elusive. Hepatitis C virus (HCV) is effective in establishing chronic infection in humans. During the last years, new direct-acting antiviral drugs (DAA) have revolutionized treatment of chronic hepatitis C, enabling rapid cure in the majority of patients. This allows us to study the influence of a chronic viral infection and its subsequent elimination on the NK cell compartment with a focus on NK cell diversity. In our recent study (Nat Commun, 9:2275), we show that chronic HCV infection irreversibly impacts human NK cell repertoire diversity

Clinical Relevance of Transjugular Liver Biopsy in Comparison with Percutaneous and Laparoscopic Liver Biopsy

Background. Transjugular liver biopsy (TJLB) is frequently used to obtain liver specimens in high-risk patients. However, TJLB sample size possibly limits their clinical relevance. Methods. 102 patients that underwent TJLB were included. Clinical parameters and outcome of TJLB were analyzed. Control samples consisted of 112 minilaparoscopic liver biopsies (mLLBs) and 100 percutaneous liver biopsies (PLBs). Results. Fewer portal tracts were detected in TJLB (4.3 ± 0.3) in comparison with PLB (11.7 ± 0.5) and mLLB (11.0 ± 0.6). No difference regarding the specification of indeterminate liver disease and staging/grading of chronic hepatitis was observed. In acute liver failure (n = 32), a proportion of hepatocellular necrosis beyond 25% was associated with a higher rate of death or liver transplantation. Conclusions. Despite smaller biopsy samples the impact on the clinical decision process was found to be comparable to PLB and mLLB. TJLB represents a helpful tool to determine hepatocellular necrosis rates in patients with acute liver failure

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders

HCV elimination; Mental health disorders; Sofosbuvir/velpatasvirEliminación del VHC; Trastornos de salud mental; Sofosbuvir/velpatasvirEliminació del VHC; Trastorns de salut mental; Sofosbuvir/velpatasvirHepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.Article processing charges, statistical support and medical writing assistance were funded by Gilead Sciences Ltd

Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008–2019

Background: Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB) patients is unknown. We aimed to determine the number of CHB patients treated with nucleos(t)ide analogs (NUCs), the treatment costs within the statutory health insurance (SHI) in Germany and per patient per month. Methods: Data on pharmacy bills of NUCs to patients with SHI between 2008 and 2019 were purchased from Insight Health™ and described. Negative binomial regression was used for trend analysis. Results: Number of patients increased between 2008 and 2019 (4.9% per year) with little changes in treatment options. Overall prescription costs were increasing (6.7% per year on average) until the introduction of tenofovir and entecavir generics in 2017 after which costs decreased by 31% in 2019. Average therapy costs peaked at 498 Euro per patient per month in 2016 and decreased to 214 Euro in 2019. Prescriptions changed from 30 to 90 pills per pack over time. HBV therapy was prescribed to 97% by three medical specialist groups, mainly specialists in internal medicine (63%), followed by hospital-based outpatient clinics (20%) and general practitioners (15%). Contrary to guideline recommendation, adefovir was still prescribed after 2011 for 1–5% of patients albeit with decreasing tendency. Prescriptions per 100,000 inhabitants were highest in Berlin and Hamburg. Conclusion: Our data shows, that the number of treated CHB patients increased steadily, while NUC therapy costs decreased. We recommend continued testing and treatment for those eligible to prevent advanced liver disease and possibly decrease further transmission of HBV.Peer Reviewe

Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections

Adaptive-like expansions of natural killer (NK) cell subsets are known to occur in response to human cytomegalovirus (CMV) infection. These expansions are typically made up of NKG2C+ NK cells with particular killer-cell immunoglobulin-like receptor (KIR) expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection. In sizeable cohorts of CMV seropositive hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infected patients, we analyzed NK cells for expression of NKG2A, NKG2C, CD57, and inhibitory KIRs to assess the appearance of NK cell expansions characteristic of what has been seen in CMV seropositive healthy individuals. Adaptive-like NK cell expansions observed in viral hepatitis patients were strongly associated with CMV seropositivity. The number of subjects with these expansions did not differ between CMV seropositive viral hepatitis patients and corresponding healthy controls. Hence, we conclude that adaptive-like NK cell expansions observed in HBV, HCV, and/or HDV infected individuals are not caused by the chronic hepatitis infections per se, but rather are a consequence of underlying CMV infection

Combination of everolimus and low-dose tacrolimus controls histological liver allograft injury as sufficiently as high-dose tacrolimus

IntroductionThe combination of everolimus (EVR) and low-dose tacrolimus (lowTAC) prevents T cell-mediated rejection of liver grafts as sufficiently as high-dose tacrolimus (highTAC) and mycophenolate, but is associated with a preserved kidney function within the first years after orthotopic liver transplantation (OLT). However, none of the available studies assessed the histological pattern of graft injury or fibrosis in surveillance biopsies (svLbx).MethodsAll svLbx taken under at least one month of stable immunosuppression with either EVR (aim 3-8 ng/ml) combined with lowTAC (aim 3-5 ng/ml) or highTAC (aim 5-8 ng/ml) combined with mycophenolate (500-1500 mg/day) within the first three to four years after OLT at our center were included. Patients who were switched to EVR because of insufficient control of alloreactivity were excluded.ResultsReasons for switches to EVR were mainly malignancies before or after OLT, or chronic kidney injury. We were able to include 20 svLbx with EVR/lowTAC and 49 with highTAC/mycophenolate. Both groups had similar liver enzymes and similar kidney function. The EVR/lowTAC group exhibited lower TAC trough levels at svLbx (4.4 vs. 6.6 ng/ml; p&lt;.001) in comparison to highTAC/mycophenolate. Histological graft injury quantified by the rejection activity index and hepatitis activity index (Ishak), as well as fibrosis were not significantly different between the EVR/lowTAC and highTAC/mycophenolate groups. Likewise, subclinical TCMR, histological criteria justifying immunosuppression minimization, and steatosis had equal prevalence in both regimens. Immunosuppression was adjusted according to the svLbx findings. Immunosuppression regimens had similarly low rates of rejection after immunosuppression reduction, when relevant graft injury was absent in the biopsy.DiscussionIn conclusion, EVR/lowTAC seems to control alloreactivity and histological graft injury as sufficiently as highTAC/mycophenolate within the first 3-4 years after OLT

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis – A pooled analysis

AbstractBackground & aimsChronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit–risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r ± DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis.MethodsTwelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r ± ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r + DSV ± RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported.ResultsIn 1066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% CI: 4.1–6.8) and 2.2% (95% CI: 1.4–3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7–2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2).ConclusionsThis pooled analysis in 1066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r ± DSV ± RBV in this population. These results support the use of OBV/PTV/r ± DSV ± RBV in this high-priority population.Lay summaryThis pooled safety analysis in 1066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was comparable to rates from historical reports for untreated patients