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Das hepatozellulare Karzinom (HCC) wird zu einer immer groser werdenden soziookonomischen Herausforderung. Internationale Leitlinien sprechen sich vorwiegend gegen die pratherapeutische Bestimmung der α‑Feto-Protein(AFP)-Konzentration aus. Bezuglich der prognostischen Aussagekraft des AFP ist die europaische Studienlage nicht aussagekraftig genug. Diese Arbeit soll mogliche Aspekte des AFP-Spiegels aufzeigen und die prognostische Vorhersagekraft des AFP-Spiegels untersuchen sowie Anregungen fur zukunftige prospektive Studien geben. Eine prospektive Leberdatenbank (n = 1382) wurde im Hinblick auf HCC-Patienten, die einen histologisch gesicherten Tumor aufweisen (n = 92), ausgewertet. Es lagen Informationen zu T‑, N‑, M‑, G‑Stadium und R‑Status bzw. zu Geschlecht, Alter, Genese vor. Fur die Analyse teilten wir das Patientengut anhand von 3 Cut-off-Werten in 6 Gruppen ein. Des Weiteren fuhrten wir eine Uberlebensanalyse mittels Kaplan-Meier und eine multifaktorielle Analyse der Einflussfaktoren auf das Outcome durch. Es gibt einen statistisch signifikanten Zusammenhang zwischen dem AFP-Spiegel, dem Tumordurchmesser (T1/2 vs. T3/4) und dem Grading (G1/G2 vs. G3/G4). In allen Gruppen fiel die Uberlebensprognose in der jeweiligen Gruppe mit dem hoheren AFP-Spiegel signifikant schlechter aus (p 8 μg/l betrug 35 Monate; bei Patienten mit AFP-Spiegeln von >200 μg/l bzw. >400 μg/l betrug das mediane Uberleben 15 Monate bzw. 11 Monate. Hohe AFP-Spiegel sind unabhangig vom T‑Stadium, Alter und R‑Status des Patienten im Vergleich zu niedrigen AFP-Spiegeln ein signifikanter Einflussfaktor fur das Outcome. Unter Berucksichtigung der vorliegenden Ergebnisse kann dem AFP-Spiegel eine therapeutische Nutzlichkeit zugeschrieben werden. Es konnten sich aus der Hohe der gemessenen AFP-Konzentration therapeutische Konsequenzen im Hinblick auf die Therapiestrategie ergeben. Demnach empfehlen wir bei allen HCC-Patienten die pra- und postoperative Bestimmung des AFP-Spiegels.

Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 x upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 x ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 x ULN and bilirubin ≤ 1 x ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004, Barcelona: 50 vs. 84%, p = 0.046, ALP &lt, 1.67x ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.

Background and Aims Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120. Methods In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed. Results Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P

Background Peginterferon alfa-2a induces durable responses in some hepatitis B e antigen-negative patients, but robust pretreatment predictors are not available to identify likely responders. In this study we aimed to develop genotype-specific baseline scoring systems to predict response. Methods Data from 323 hepatitis B e antigen-negative peginterferon alfa-2a recipients from three studies were analyzed. Scoring systems were developed using generalized additive models and multiple logistic regression analysis. Response was defined as hepatitis B virus DNA

Thomas Harlans veröffentlichtes Werk umfasst ein Theaterstück Ich selbst und kein Engel (1958), Filme Torre Bela (1975), Wundkanal (1984) und Prosa, die Romane Rosa (2000) und Heldenfriedhof (2006), den Prosaband Die Stadt Ys (2007) sowie den posthum erschienenen Text Veit (2011). Vor allem für seine Prosa sind zwei biografische Aspekte thematisch bestimmend: Der Holocaust und das deswegen schwer belastete Verhältnis zum Vater, Veit Harlan. Der Sohn hat ihm seinen Film Jud Süß nicht verzeihen können. Das wird im Veit, ein Text in Form eines Briefs an den Vater, noch einmal, also am Ende seines Lebens, Thomas Harlans zentrales Thema, verknüpft mit dem Holocaust, dessen propagandistische Vorbereitung durch den Film der Sohn dem Vater vorhält.

Background & Aims There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Methods Non-cirrhotic HBeAg-negative patients who had received TDF for ≥4years, with suppressed HBV DNA for ≥3.5years, were randomly assigned to either stop (n=21) or continue (n=21) TDF monotherapy. Standard laboratory tests including HBV DNA viral load, HBsAg and alanine aminotransferase (ALT) measurements, and adverse event reporting were carried out during treatment and post-treatment follow-up for 144weeks. Results Of the patients who stopped TDF therapy, 62% (n=13) remained off-therapy to Week 144. Median HBsAg change in this group was −0.59log 10 IU/ml (range −4.49 to 0.02log 10 IU/ml) vs. 0.21log 10 IU/ml in patients who continued TDF therapy. Four patients (19%) achieved HBsAg loss. Patients stopping therapy had initial fluctuations in viral load and ALT; however, at Week 144, 43% (n=9) had either achieved HBsAg loss or had HBV DNA Conclusions This controlled study demonstrated the potential for HBsAg loss and/or sustained virological response in non-cirrhotic HBeAg-negative patients stopping long-term TDF therapy. Lay summary: Nucleos(t)ide analogue (NA) is usually a life-long therapy for HBV patients. This randomised controlled study investigated the discontinuation of tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144, of which 43% of patients had achieved either HBsAg loss or HBV DNA Clinical trial number: NCT01320943.

Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide.

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive or negative chronic hepatitis, who are treatment-naive or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV 'functional cure', the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.

Background & Aims Tenofovir disoproxil fumarate (TDF) is a first‐line treatment for chronic hepatitis B (CHB). We aimed to describe the efficacy and safety profiles of TDF treatment for up to 10 years in a well‐described cohort of CHB patients. Methods Hepatitis B e antigen (HBeAg)‐negative and HBeAg‐positive patients from two randomised, double‐blind trials (ClinicalTrials. gov: NCT00117676 and NCT00116805) completed 48 weeks of randomised treatment with TDF or adefovir dipivoxil. A subset of these patients was then eligible to receive open‐label TDF treatment for up to 10 years. At Year 10, patients were assessed for virological suppression, alanine aminotransferase (ALT) normalisation, serological response, safety, and tolerability. Results Of 641 randomised and treated patients, 585 (91%) entered the open‐label extension phase with 203 (32%) patients completing Year 10 of the study. At Year 10, 118/118 (100%) of HBeAg‐negative patients and 78/80 (98%) of HBeAg‐positive patients with available data achieved hepatitis B virus (HBV) DNA

SummaryBackground 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. Aim To validate the use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection under real-word conditions. Methods The German Hepatitis C-Registry is a large national non-interventional real-world study for patients with chronic hepatitis C. A total of 1322 GT3 patients were enrolled (211 untreated and 1111 treated patients). Results Between February 2014 and September 2015, five different treatment strategies have been used (PegIFN+RBV, PegIFN+RBV+SOF, SOF+RBV, DCV+SOF±RBV, LDV/SOF±RBV). Treatment uptake and use of treatment concepts changed markedly and rapidly during the study influenced by new approvals, guideline recommendations, and label updates. PegIFN-based therapies constantly declined while DCV-based therapies increased with one interruption after the approval of LDV/SOF, which was frequently used until new guidelines recommended not using this combination for GT3. Per-protocol SVR ranged from 80.9% in the PegIFN+RBV group to 96.1% in PegIFN+RBV+SOF treated patients. Treatment-experienced patients with cirrhosis showed a suboptimal SVR of 68% for SOF+RBV but a high SVR of 90–95% for DCV+SOF±RBV. The safety analysis showed more adverse events and a stronger decline of haemoglobin for RBV containing regimens. Conclusions Real-world data can validate the effectiveness and safety for treatment regimens that had previously been approved with limited data, in particular for specific subgroups of patients. The present study demonstrates how rapid new scientific data, new treatment guidelines, new drug approvals and label changes are implemented into routine clinical practice today.

BACKGROUND AND AIM: The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of alanine aminotransferase (ALT) flares during long-term entecavir (ETV) in chronic hepatitis B (CHB). METHODS: CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as \textgreater 3x increase in ALT compared with baseline or lowest on-treatment level and an absolute ALT \textgreater 3x ULN. Flares were designated as host-induced (preceded by hepatitis B virus (HBV)-DNA decline), virus-induced (HBV-DNA increase), or indeterminate (stable HBV-DNA). RESULTS: Seven hundred and twenty-nine patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline hepatitis B e antigen (HBeAg)-positivity (HR 2.84; P = 0.005) and high HBV-DNA (Hazard ratio (HR) 1.30; P = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs 83 weeks; P = 0.027) or indeterminate flares (15 vs 109 weeks; P = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and hepatitis B surface antigen (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1). CONCLUSION: The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares

Background HIV–HCV-coinfected patients respond just as well to modern direct-acting antiviral HCV therapy as HCV-monoinfected patients. However, clinical data for all-oral HCV treatments are sparse in HIV–HCV-coinfected patients with an advanced stage of liver cirrhosis. Methods A subanalysis of efficacy and safety for a daclatasvir (DCV) and sofosbuvir (SOF) regimen, with or without ribavirin (RBV), was undertaken in HIV–HCV-coinfected patients with advanced liver disease and no other treatment options enrolled into a European DCV compassionate use programme. Results Fifty five HIV–HCV (mostly genotypes 1, 3, 4) coinfected patients were treated with DCV+SOF with ( n=16) or without RBV ( n=39), mostly for 24 weeks. Patients were predominantly (95%) cirrhotic (50% were Child–Pugh class B or C) and were receiving a wide range of antiretrovirals; 40% were injection drug users and 25% were receiving oral opioid substitution. Sustained virological response at post-treatment week 12 (SVR12) by modified intention-to-treat analysis ( n=52) was 92% overall (95% CI 81.5, 97.9), and was similar with (94% [95% CI 69.8, 99.8]) or without RBV (92% [95% CI 77.5, 98.2]). Only one patient relapsed (Child–Pugh class B). The overall SVR12 rate after excluding non-virologi-cal failures ( n=49) was 98% (95% CI 89.1, 99.9). Four patients discontinued treatment for adverse events and one died during treatment (not treatment-related). No patient lost opioid maintenance or required a change of antiretrovirals due to drug–drug interactions. Conclusions DCV+SOF, with or without RBV, showed high SVR12 rates and was well tolerated in this real-world cohort of HIV–HCV-coinfected patients with very advanced liver disease. ClinicalTrials.gov ID NCT02097966 (Study AI444-237).

In spite of a decrease in the prevalence and incidence seen in recent years, chronic hepatitis B (CHB) still remains a major healthcare challenge, prevalent mostly in developing but also in developed regions. CHB is associated with significant morbidity and mortality, secondary to the complications of disease progression; cirrhosis and hepatocellular carcinoma (HCC). Historically, antiviral treatment has been restricted to patients with active hepatitis, established liver disease, fibrosis or cirrhosis and/or the risk of HCC development. As a result, patients with hepatitis B 'e' antigen (HBeAg) -positive chronic infection, formerly referred to as the 'immune tolerant' disease phase, have been excluded from treatment, since immune tolerant CHB had been considered 'benign' with no ostensible progressive liver disease. However, recent advances in 'decoding' the immunopathogenesis of CHB challenged the accuracy of this classical perception: it is now well-recognised that HBeAg-positive chronic infection is not characterized by immunological tolerance and that events associated with tumourigenesis are already present during this early disease phase. These findings have led to a paradigm shift: in 2017, the European Association for the Study of the Liver (EASL) recommended a change in the nomenclature and clinical categorisation of CHB and proposed lowering the threshold for antiviral treatment to include patients with HBeAg-positive chronic infection. It is anticipated that this could delay or even prevent disease progression and the development of HCC, alongside the potential to achieve functional cure (hepatitis B 'surface' antigen loss with or without development of hepatitis B 'surface' antibody). The current article reviews relevant literature and discusses the reasons for considering early treatment in CHB.

Norursodeoxycholic acid is an orally administered side chain-shortened homologue of ursodeoxycholic acid that undergoes hepatic enrichment with hepatoprotective, anti-inflammatory, and antifibrotic activity. We assessed the efficacy of two doses of norursodeoxycholic acid versus placebo for the treatment of non-alcoholic fatty liver disease.We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 dose-finding clinical trial in tertiary referral hospitals and medical centres in Austria (n=6) and Germany (n=23) for patients with non-alcoholic fatty liver disease with or without diabetes. Patients with a clinical diagnosis of non-alcoholic fatty liver disease and serum alanine aminotransferase (ALT) concentrations of more than 0·8 times the upper limit of normal were randomly assigned (1:1:1) using a computer-generated central randomisation. Patients were randomly assigned to receive either norursodeoxycholic acid capsules at 500 mg per day or 1500 mg per day, or placebo, for 12 weeks with a subsequent 4-week follow-up period. All individuals involved in the trial were masked to treatment allocation. The primary efficacy endpoint was the mean relative percentage change in ALT concentrations between baseline and end of treatment assessed in the intention-to-treat population. This trial is registered with EudraCT, number 2013-004605-38.Between March 30, 2015, and Sept 20, 2016, of 198 individuals included in the analysis, 67 patients were randomly assigned to receive 500 mg norursodeoxycholic acid, 67 to 1500 mg norursodeoxycholic acid, and 64 to placebo. A dose-dependent reduction in serum ALT between baseline and end of treatment was observed with norursodeoxycholic acid versus placebo, with a significant effect in the 1500 mg group (mean change -27·8%, 95% repeated CI -34·7 to -14·4; p0·0001). Serious adverse events (n=6) and treatment-emergent adverse events (n=314) were reported in a similar proportion of patients across groups. 112 treatment-emergent adverse events occurred in the 1500 mg group, 99 in the 500 mg group, and 103 in the placebo group. The most frequent adverse events were headache, gastrointestinal disorders, and infections (eg, diarrhoea, abdominal pain, or nasopharyngitis).Norursodeoxycholic acid at 1500 mg resulted in a significant reduction of serum ALT within 12 weeks of treatment when compared with placebo. Norursodeoxycholic acid was safe and well tolerated encouraging further studies.Dr Falk Pharma GmbH.

There are only limited data on sofosbuvir-based treatment regimens in hepatitis C virus (HCV) genotype 4-infected patients.To evaluate safety and efficacy of sofosbuvir-based triple-therapy in HCV genotype 4 infection.All HCV genotype 4-infected patients who started sofosbuvir-based triple-therapy at our two centres between January and June 2014 were prospectively included (N=24) and compared to genotype 4 patients treated with peginterferon/ribavirin between January 2001 and December 2012 (N=63).The demographics in the sofosbuvir group and the controls were comparable (males 87.5% and 82.5%; mean age 46.7±9.0 years and 42.0±9.8 years, respectively). Sustained virological response was achieved in 83.3% in the sofosbuvir group and in 47.6% of controls (P=0.003). Fatigue (P=0.007), flu-like (P=0.015), gastrointestinal (P0.001), dermatologic (P0.001) and psychiatric symptoms (P=0.022) were more common in the control group.In our real-life cohort, sofosbuvir-based triple therapy confirmed its high efficacy and safety for chronic genotype 4 hepatitis C.

Deutsche Gesellschaft fur Gastroenterologie, Verdauungsund Stoffwechselkrankheiten (DGVS), Berufsverband niedergelassener Gastroenterologen (bng), Kompetenznetz Hepatitis / Deutsche Leberstiftung, Deutsche Gesellschaft fur Pathologie (DGP), Berufsverband Deutscher Pathologen, Gesellschaft fur Virologie (GfV), Gesellschaft fur Padiatrische Gastroenterologie und Ernahrung (GPGE), Schweizerische Gesellschaft fur Gastroenterologie (SGG), Osterreichische Gesellschaft fur Gastroenterologie und Hepatologie (OGGH), Deutsche Transplantationsgesellschaft (DTG), Deutsche Leberhilfe e.V.

Background Hepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population. Methods We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network. Results A total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82-212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (p

Background & Aims Little is known about substitutions that mediate resistance of hepatitis C virus (HCV) to direct-acting antivirals (DAAs), due to the small number of patients with treatment failure in approval studies. It is important to identify resistance patterns to select effective salvage treatments. Methods We performed a comprehensive analysis for resistance-associated substitutions (RASs) in HCV genes (nonstructural protein [NS]3, NS5A, NS5B) targeted by DAAs. We compared NS3, NS5A, and NS5B sequences from 626 patients in Europe with DAA failure with sequences from 2322 DAA-naive patients, infected with HCV genotypes 1 to 4. We considered RASs to be relevant if they were associated with DAA failure in patients or conferred a greater than twofold change in susceptibility compared with a reference strain in in vitro replicon assays. Data were collected on pretreatment status, DAA regimen, the treatment initiation date and duration, and virologic response. Patients who received at least 4 weeks of antiviral treatment were included in the analysis. Results RASs in NS3 associated with simeprevir or paritaprevir failure include R155K and D168E/V. In addition, several RASs were specifically associated with failure of simeprevir (Q80K/R in patients with genotype 1a or 4) or paritaprevir (Y56H in combination with D168V in patients with genotype 1b). Y93H in NS5A was the RAS most frequently associated with failure of daclatasvir, ledipasvir, or ombitasvir in patients with genotype 1b infection, and L31M was associated with failure of daclatasvir or ledipasvir, but not ombitasvir. RASs in NS5A were heterogeneous among patients with HCV genotype 1a or genotype 4 infections. In patients with HCV genotype 3, Y93H was associated with resistance to daclatasvir, but no RASs were associated with ledipasvir failure, pointing to a limited efficacy of ledipasvir in patients with genotype 3. Among patients failed by sofosbuvir-containing regimens, L159F was enriched in patients with genotype 1b (together with C316N) or genotype 3 infection, whereas the RAS S282T was rarely observed. Conclusions We compared RASs in NS3, NS5A, and NS5B among patients failed by DAA therapy. Theses varied with the HCV genotype and subtype, and the different drug classes. These findings might be used to select salvage therapies.

Background & Aims We evaluated the antiviral response of Asian or Pacific Islander (API) patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as pre-treatment hepatitis B virus (HBV) DNA ≥9 log10 copies/ml, following up to 288 weeks of tenofovir disoproxil fumarate (TDF) treatment. Methods A total of 205 HBeAg-negative and HBeAg-positive self-described API patients received 48 weeks of TDF 300 mg (HVL n = 18) or adefovir dipivoxil 10 mg (HVL n = 15) in a blinded fashion, followed by open-label TDF for an additional 240 weeks. The proportions of HVL vs. non-HVL patients with HBV DNA

Universitatsklinikum Frankfurt am Main, Med. Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main. Email: sarrazin@em.uni-frankfurt.de 2 Sektion Hepatologie; Klinik fur Gastroenterologie und Rheumatologie, Universitatsklinikum Leipzig 3 Leberzentrum Hamburg im IFI an der Askleopios Klinik St. Georg, Lohmuhlenstrase 5, 20099 Hamburg 4 Universitatsklinikum Ulm 5 GastroenterologischHepatologisches Zentrum Kiel, Preetzer Chaussee 134, 24146 Kiel 6 Gastroenterologische Gemeinschaftspraxis Herne, Wiescherstr. 20, 44623 Herne 7 Medizinische Hochschule Hannover 8 Zentrum fur HIV und Hepatogastroenterologie, Grafenberger Allee 128a, 40237 Dusseldorf 9 MVZ fur Gastroenterologie und Hepatologie, Franz-Kail-Str. 2, 51375 Leverkusen