Melanesia holds the world's most diverse and intact insular amphibian fauna.

Identifying hotspots of biological diversity is a key step in conservation prioritisation. Melanesia-centred on the vast island of New Guinea-is increasingly recognised for its exceptionally species-rich and endemic biota. Here we show that Melanesia has the world's most diverse insular amphibian fauna, with over 7% of recognised global frog species in less than 0.7% of the world's land area, and over 97% of species endemic. We further estimate that nearly 200 additional candidate species have been discovered but remain unnamed, pointing to a total fauna in excess of 700 species. Nearly 60% of the Melanesian frog fauna is in a lineage of direct-developing microhylids characterised by smaller distributions than co-occurring frog families, suggesting lineage-specific high beta diversity is a key driver of Melanesian anuran megadiversity. A comprehensive conservation status assessment further highlights geographic concentrations of recently described range-restricted threatened taxa that warrant urgent conservation actions. Nonetheless, by world standards, the Melanesian frog fauna is relatively intact, with 6% of assessed species listed as threatened and no documented extinctions; and thus it provides an unparalleled opportunity to understand and conserve a megadiverse and relatively intact insular biota.

Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study.

Background: Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods: A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results: Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion: Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates.

BACKGROUND Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany. Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. MATERIAL AND METHODS All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. RESULTS Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. CONCLUSIONS PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates.

Percutaneous creation of direct intrahepatic portosystemic shunts - an alternative for failed TIPS creation.

INTRODUCTION: Direct intrahepatic portosystemic shunt creation is a feasible and safe alternative for transjugular intrahepatic portosystemic shunt creation. It needs equipment like endovascular ultrasound with restricted availability. We performed the procedure percutaneously with a common interventional armamentarium to make it more feasible. METHODS: Retrospective analysis of 8 percutaneous DIPS insertions between 2016 and 2020. RESULTS: The procedure was successful in 8/8 patients. There was no short-term death reported within 30 days. The longest reported patency is 5 years. CONCLUSION: Percutaneous DIPS creation is a feasible alternative for failed TIPS. Percutaneously the procedure can be completed faster than conventional DIPS using only minimal puncture equipment. LEVEL OF EVIDENCE: Level 4, Case Series.

Extensive intrathoracic and intraperitoneal splenosis mimicking mesothelioma: a case report.

BACKGROUND: Splenosis is the heterotopic autotransplantation of splenic tissue after severe splenic trauma and/or splenectomy. The epidemiology is elusive, but splenosis is frequently misdiagnosed as malignant tumors of gastrointestinal, gynecological, or hematological origin before the correct diagnosis is ultimately found. We herein report a rare case of combined, extensive intraabdominal and intrathoracic splenosis initially presenting as pleural mesothelioma. CASE PRESENTATION: A 63-year-old Caucasian male presented with dyspnea and recurring thoracic pain. Initial X-ray and computed tomography scans showed disseminated intrathoracic and intraabdominal lesions. Consequently, thoracoabdominal mesothelioma or a polytopically metastasized cancer of unknown origin was suspected. A thorough examination of the patient's medical history and contrast-enhanced ultrasound by a skilled examiner revealed the diagnosis of extensive abdominal and thoracic splenosis as a consequence of an abdominal gunshot wound with a ruptured diaphragm several decades earlier. Timely diagnosis by noninvasive measures prevented the patient from potential complications of harmful diagnostic procedures, including nuclear imaging and biopsies. The patient is currently treated for hepatitis C and chronic obstructive lung disease, whereas no specific treatment for splenosis is required. CONCLUSIONS: We present a case of rare intrathoracic and intraperitoneal splenosis mimicking mesothelioma. Contrast-enhanced ultrasound and thorough patient history were used for diagnosis and prevented this patient from having to undergo potentially harmful diagnostics. Splenosis can occur after splenic trauma and, consequently, needs to be considered as a rare differential diagnosis to malignant tumors of various origins when a matching patient history is obtained.

Only partial improvement in health-related quality of life after treatment of chronic hepatitis C virus infection with direct acting antivirals in a real-world setting-results from the German Hepatitis C-Registry (DHC-R).

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.

Indication of Liver Transplantation for Hepatocellular Carcinoma Should Be Reconsidered in Case of Microvascular Invasion and Multilocular Tumor Occurrence.

Liver transplantation (LT) is routinely performed for hepatocellular carcinoma (HCC) in cirrhosis without major vascular invasion. Although the adverse influence of microvascular invasion is recognized, its occurrence does not contraindicate LT. We retrospectively analyzed in our LT cohort the significance of microvascular invasion on survival and demonstrate bridging procedures. At our hospital, 346 patients were diagnosed with HCC, 171 patients were evaluated for LT, and 153 were listed at Eurotransplant during a period of 11 years. Among these, 112 patients received LT and were included in this study. Overall survival after 1, 3 and 5 years was 86.3%, 73.9%, and 67.9%, respectively. Microvascular invasion led to significantly reduced overall (p = 0.030) and disease-free survival (p = 0.002). Five-year disease-free survival with microvascular invasion was 10.5%. Multilocular tumor occurrence with simultaneous microvascular invasion revealed the worst prognosis. In our LT cohort, predominant bridging treatment was transarterial chemoembolization (TACE) and the number of TACE significantly correlated with poorer overall survival after LT (p = 0.028), which was confirmed in multiple Cox regression analysis for overall and disease-free survival (p = 0.015 and p = 0.011). Microvascular tumor invasion is significantly associated with reduced prognosis after LT, which is aggravated by simultaneous occurrence of multiple lesions. Therefore, indication strategies for LT should be reconsidered.

A new species of large green treefrog (Litoria, Pelodryadidae) from Papua, Indonesia.

We describe a new species of large green treefrog from southern Papua Province, Indonesia. Litoria lubisi sp. nov. is placed in the L. infrafrenata Group based on its size, colouration and configuration of hand webbing, but differs from other members of this group in aspects of body size and proportions, extent of hand webbing, colouration and male advertisement call. Litoria lubisi sp. nov. occurs in close proximity to two other species in the L. infrafrenata Group, emphasising an until-recently overlooked pattern that multiple species of large, arboreal Litoria have overlapping distributions across much of the lowlands of southern New Guinea.

Inferior Vena Cava Constriction After Liver Transplantation Is a Severe Complication Requiring Individually Adapted Treatment: Report of a Single-Center Experience.

BACKGROUND Reports on vena cava occlusion after liver transplantation (LT) are rare, but this finding represents a severe complication in the early postoperative period. In the context of the complex presentation of a patient after LT, symptoms are often misinterpreted and can be subtle. MATERIAL AND METHODS In our cohort of 138 LTs performed between 2014 and 2017 at our University's Transplantation Department, 117 transplantations were valid for further analysis after exclusion of pediatric transplantations and transplants with primary non-function grafts. In 101 cases (73%), patients received a deceased-donor full-size organ. Living-donor LT was performed in 8 patients (6.4%) and 8 patients (6.4%) received a split graft. We report on 6 patients who had inferior vena cava (IVC) occlusion and summarize the treatment choices. RESULTS In our series, patients with positive findings (age 38-70 years) received an orthotopic full-size deceased-donor graft with end-to-end IVC anastomosis. In the subsequent period, imaging revealing IVC occlusion was done on a follow-up basis (n=2), due to dyspnea (n=1), and for progressive ascites (n=2). In 3 cases, a thrombus was found. We give detailed information on our treatment options from interventional treatment to transcardial thrombus removal and anastomosis augmentation. CONCLUSIONS IVC constriction and subsequent thrombosis are severe complications after LT that require individually adapted treatment in specialized centers. Since patients often present with subclinical symptoms, vascular diagnosis should be performed early to detect caval anastomosis pathologies. Despite regular ultrasonography, we favor CT and cavography for subsequent quantification. We also review the literature on IVC occlusion after LT.

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy - data from the German hepatitis C registry (DHC-R).

BACKGROUND: Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described. PATIENTS AND METHODS: Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available. RESULTS: Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %). CONCLUSIONS: Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.

Lethal thrombosis of the iliac artery caused by Aspergillus fumigatus after liver transplantation: case report and review of the literature.

BACKGROUND: Aspergillus fumigatus infections frequently occur after solid organ transplantation. Yet, a fungal thrombosis after liver transplantation is an exceptional finding. CASE PRESENTATION: We report on a 44-year-old female with an aspergillosis after liver transplantation for autoimmune hepatitis. On postoperative day (pod) 7, seizures occurred and imaging diagnostics revealed an intracranial lesion. Anidulafungin was initiated in suspicion of mycosis and switched to voriconazole on suspicion of an Aspergillus spp. infection. Progression of the cerebral lesion prompted craniotomy (pod 48) and the aspergillosis was verified. The patient was discharged with oral voriconazole therapy. Re-admission was necessary with acute-on-chronic renal failure after a tacrolimus overdose on pod 130. The patient received a pelvic angiography due to a temperature difference in the legs. It showed a complete iliac artery thrombosis which was subsecutively surgically removed. The histopathological examination revealed an Aspergillus fumigatus conglomerate. The patient died on pod 210 due to systemic aspergillosis. CONCLUSION: The acute development of focal neurologic deficits is common in patients with an aspergillosis of the brain. Nevertheless, arterial thrombosis after Aspergillus fumigatus is less frequent and, to the best of our knowledge, its occurrence after liver transplantation has not yet been reported so far. Due to its rarity, we added a review of the literature to this manuscript.

Systematics of New Guinea treefrogs (Litoria: Pelodryadidae) with erectile rostral spikes: an extended description of Litoria pronimia and a new species from the Foja Mountains.

A small number of treefrog species (Litoria) from Melanesia are unusual amongst Anura in having distinctive fleshy rostral spikes. Here, we first present an extended description for Litoria pronimia Menzies, a small species that is widespread along the southern edge of the Central Cordillera of New Guinea, and in which males have a long and erectile rostral spike. Second, we describe Litoria pinocchio sp. nov. a new, morphologically similar, yet geographically disjunct species from the Foja Mountains in northern Papua Province, Indonesia. The new species differs from Litoria pronimia in aspects of body shape, proportions and colouration. A review of variation in the size, structure and degree of sexual dimorphism of the rostral spike across different species of Litoria suggests varying function including mate selection and camouflage.

Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register).

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.

[4 years of direct-acting antivirals (DAAs) in the German Hepatitis C-Registry (DHC-R)]. / Deutsches Hepatitis C-Register (DHC-R) ­ eine Zwischenbilanz 4 Jahre nach Zulassung direkt antiviraler Substanzen (DAAs).

BACKGROUND: More than 250 000 patients suffer from chronic hepatitis C in Germany. Several potent, direct-acting antiviral drugs have been approved since 2014. The aim of the German Hepatitis C-Registry (DHC-R) is to describe the epidemiology and patient care of hepatitis C and to investigate the efficacy and safety of new treatment options in real-world settings. METHODS: The DHC-R is a prospective multicenter non-interventional registry study that includes 327 centers throughout Germany. All approved treatment options have been documented. The current analysis differentiated 4 phases: 2/2014 - 12/2014, 1/2015 - 12/2015, 1/2016 - 7/2017 and 8/2017 - 7/2018. FINDINGS: Between February 2014 and July 2018, 12 170 patients were included in the registry (61.3 % male), and antiviral treatment was initiated in 11 268. The mean age declined from 52.3 years (phase 1) to 49.3 years (phase 4), while the proportion of patients with previous or ongoing drug abuse increased (26.3 % to 43.1 %). In 2014, 35.1 % of treated patients had liver cirrhosis, which declined to 16.5 % in phase 4. The HCV genotype distribution showed marked fluctuations, with most recent increases in HCV genotype 3 (30 % in phase 4). Per-protocol sustained virological response rates increased from 92.8 % in 2014 to 94.4 % in 2017/18 with excellent tolerability. SUMMARY: The DHC-R mirrors patient care of chronic hepatitis in the real-world setting in Germany and provides insights into epidemiology developments. It also confirms the high efficacy and safety of novel treatment options.

Estimation of liver fibrosis by noncommercial serum markers in comparison with transient elastography in patients with chronic hepatitis C virus infection receiving direct-acting antiviral treatment.

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.

Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients.

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.

Real-world effectiveness of 8-week treatment with ledipasvir/sofosbuvir in chronic hepatitis C.

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 naïve 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. LAY SUMMARY: In a large real-world cohort of patients mainly treated by physicians in private practice in Germany, shorter HCV treatment (8-week) resulted in equivalent cure rates to 12-week treatment in genotype 1 HCV-infected patients. Thus, shorter treatment can be recommended in these patients which would substantially reduce costs of therapy. Clinical Trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy.

BACKGROUND: Neurological disorders due to calcineurin inhibitor (CNI) treatment pose a well-known problem after liver transplantation (LTx). In this study, the impact of CNIs on cognitive functioning during maintenance therapy was analyzed. A possible improvement of cognitive functioning, compliance and health-related quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation was prospectively assessed. METHODS: In a cross-section analysis cognitive functioning of living donors (LD), waiting list patients and LTx patients was tested using a 4 times trail making test (4-TTMT). In a further investigator-initiated trial a possible improvement of cognitive functioning, HRQoL and compliance after conversion to the once-daily tacrolimus formulation was prospectively assessed over 1 year. HRQoL was assessed using an EORTC-QLQ C30 questionnaire and patient's compliance was assessed by the Basel Assessment of Compliance with Immunosuppressive Medication Scales questionnaire. Correlated data were sex, age, time after surgery, liver disease, model of end-stage liver disease score, creatinine, CNI type, and CNI trough levels. RESULTS: Two hundred eleven patients were included in this cross-section analysis. Twenty-seven patients agreed to participate in the investigator-initiated trial. LTx patients completed the 4-TTMT slower than living donor patients and faster than waiting list patients. Patients with twice daily cyclosporine A (CSA) formulation needed longer to finish the 4-TTMT than patients with the once-daily tacrolimus formulation. After drug conversion of a twice-daily CNI formulation to a once-daily tacrolimus formulation, CSA-treated patients needed longer to improve their cognitive functioning. HRQoL and compliance did not improve after drug conversion. CONCLUSIONS: Patients with once-daily tacrolimus formulation had a better psychomotor speed than CSA-treated patients. The conversion to once-daily tacrolimus formulation significantly improved cognitive functioning, but had no impact on HRQoL or compliance.

Treatment of HCV genotype 2 with sofosbuvir and ribavirin results in lower sustained virological response rates in real life than expected from clinical trials.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infections with genotype 2 (GT2) are generally considered as easy to treat. The current standard therapy is 12 weeks of sofosbuvir and ribavirin. However, sustained virological response (SVR) rates varied substantially in distinct subgroups. Therefore, re-assessing the efficacy of interferon-free therapy in cohorts with larger patient numbers is warranted. METHODS: The German Hepatitis C registry is a national multicenter cohort. Patients are treated at the discretion of the physician. Data are collected by a web-based data system and confirmed by plausibility checks and on-site monitoring. RESULTS: A total of 265 (4.3%) of 6034 patients enrolled in the registry were infected with GT2, and 236 had initiated treatment (60% males, 98% Caucasian, median age 54 years). Treatment with sofosbuvir and ribavirin for 12 weeks achieved SVR at week 12 post-treatment (SVR12) in 136/164 (83%) patients. SVR12 rates for this regimen were 80% (35/44) in treatment-experienced patients, 74% (20/27) in cirrhotics and 75% (21/28) in patients with HCV-RNA ≥6 million IU/mL. The overall SVR rate in patients treated with sofosbuvir/ribavirin 12 weeks per protocol (PP), excluding therapy discontinuation or lost to follow-up, was 135/151 (89%). PP SVR12 rates were 91% for treatment naïve, 83% for cirrhotic and 80% for treatment-experienced patients respectively. CONCLUSIONS: In this large GT2 cohort, sofosbuvir and ribavirin for 12 weeks achieved lower SVR rates compared to treatment outcomes expected from phase 3 trials. These findings highlight the need for establishing alternative treatment strategies for GT2 patients, especially in patients with unfavourable outcome factors.