Solubilizing Benzodifuranone-Based Conjugated Copolymers with Single-Oxygen-Containing Branched Side Chains.

Single-oxygen-containing branched side chains are designed and used to solubilize n-type copolymers consisting of BDF (benzodifuranone), isatin, and thiophene-based units. We present a simple synthetic approach to side chains with varying linker distances between the backbone and the branching point. The synthetic pathway is straightforward and modular and starts with commercially available reagents. The side chains give rise to excellent solubilities of BDF-thiophene copolymers of up to 90 mg/mL, while still being moderate in size (26-34 atoms large). The excellent solubility furthermore allows high molar mass materials. BDF-thiophene copolymers are characterized in terms of optoelectronic and thermoelectric properties. The electrical conductivity of chemically doped polymers is found to scale with molar mass, reaching ∼1 S/cm for the highest molar mass and longest backbone-branching point distance.

Five-year follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D.

BACKGROUND & AIMS: Until recently, pegylated interferon-alfa-2a (PEG-IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG-IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short-term relapses within 24 weeks. The virological and clinical long-term effects after prolonged PEG-IFNa-based treatment of hepatitis D are unknown. METHODS: In the HIDIT-II study patients (including 40% with liver cirrhosis) received 180 µg PEG-IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 µg PEG-IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy). RESULTS: Until the end of follow-up, 16 (13%) patients developed liver-related complications (PEG-IFNa + TDF, n = 5 vs PEG-IFNa + placebo, n = 11; p = .179). Achieving HDV suppression at week 96 was associated with decreased long-term risk for the development of hepatocellular carcinoma (p = .04) and hepatic decompensation (p = .009). Including complications irrespective of PEG-IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG-IFNa (16/102, p > .999) but was associated with a higher chance of HDV-RNA suppression (p = .024, odds ratio 3.9 [1.3-12]). CONCLUSIONS: Liver-related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG-IFNa treatment. PEG-IFNa treatment should be recommended to HDV-infected patients until alternative therapies become available. Retreatment with PEG-IFNa should be considered for patients with inadequate response to the first course of treatment. CLINICAL TRIAL REGISTRATION: NCT00932971.

Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial.

BACKGROUND & AIMS: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta. METHODS: Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available. RESULTS: Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL. CONCLUSIONS: Overall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life.

Comment on Depoorter, L.; Vandenplas, Y. Probiotics in Pediatrics. A Review and Practical Guide. Nutrients 2021, 13, 2176.

We read the review by Depoorter et al. [...].

Clinical effectiveness of bidirectional fecal microbiota transfer in the treatment of recurrent Clostridioides difficile infections.

BACKGROUND: Fecal microbiota transfer (FMT) has become a standard of care in the prevention of multiple recurrent Clostridioides difficile (rCDI) infection. AIM: While primary cure rates range from 70-80% following a single treatment using monodirectional approaches, cure rates of combination treatment remain largely unknown. METHODS: In a retrospective case-control study, outcomes following simultaneous bidirectional FMT (bFMT) with combined endoscopic application into the upper and lower gastrointestinal tract, compared to standard routes of application (endoscopy via upper or lower gastrointestinal tract and oral capsules; abbreviated UGIT, LGIT and CAP) on day 30 and 90 after FMT were assessed. Statistical matching partners were identified using number of recurrences (<3; ≥3), age and gender. RESULTS: Primary cure rates at D30 and D90 for bFMT were 100% (p=.001). The matched control groups showed cure rates of 81.3% for LGIT (p=.010), 62.5% for UGIT (p=.000) and 78.1% for CAP (p=.005) on D30 and 81.3% for LGIT (p=.010), 59.4% for UGIT (p=.000) and 71.9% for CAP (p=.001) on D90. CONCLUSION: In our analysis, bFMT on the same day significantly increased primary cure rate at D30 and D90. These data require prospective confirmation but suggest that route of application may play a significant role in optimizing patient outcomes. ClinicalTrials.gov no: NCT02681068.

Residual low HDV viraemia is associated HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis delta: Results from the HIDIT-II study.

The role of low levels of HDV-RNA during and after interferon therapy of hepatitis D is unknown. We re-analysed HDV RNA in 372 samples collected in the HIDIT-2 trial (Wedemeyer et al, Lancet Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in-house assay (IA). We detected HDV-RNA in one-third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post-treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. In contrast, the post-treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment.

A transient early HBV-DNA increase during PEG-IFNα therapy of hepatitis D indicates loss of infected cells and is associated with HDV-RNA and HBsAg reduction.

HBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFNα on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFNα-2a plus tenofovir-disoproxil-fumarate (PEG-IFNα/TDF, n = 59) or placebo (PEG-IFNα/PBO; n = 61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFNα/PBO-treated patients but also in 76% of PEG-IFNα/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFNα/TDF-treated and 12 PEG-IFNα/PBO-treated patients. This increase was positively associated with HBsAg loss [(P = 0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P = 0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFNα-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFNα-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.

Hand-foot syndrome induced changes of the palmar epidermal ridge configurations during and after treatment with capecitabine.

Palmar plantar erythrodysesthesia (hand-foot syndrome, HFS) is a common adverse event of treatment with cytostatic chemotherapeutics such as capecitabine. Histopathological findings are nonspecific and may even include generalized epidermal necrolysis. A total of 50 patients were examined before and after the intake of capecitabine to assess if HFS may result in relevant changes of the palmar epidermal ridge configurations with possible consequences for the patients who want to travel abroad. In total, 14 of the 50 patients developed HFS (28%) with HFS grades 1-3 observed. HFS grade 4 was not observed. HFS of grade 2 and 3 was associated with a temporary macroscopic loss of the epidermal ridges. No dactyloscopic changes that might have led to a false identification were seen in those cases. Patients with a risk of HFS development who want to travel abroad should carry a medical pass of the chemotherapeutic treatment to prevent them from difficulties in identification controls.

The impact of technical and clinical factors on fecal microbiota transfer outcomes for the treatment of recurrent Clostridioides difficile infections in Germany.

Introduction: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent Clostridioides difficile infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany. Methods: Information was extracted from the MicroTrans Registry (NCT02681068), a retrospective observational multicenter study, collecting data from patients undergoing FMT for recurrent or refractory CDI in Germany. We performed binary logistic regression with the following covariates: age, gender, ribotype 027, Eastern Co-operative Oncology Group score, immunosuppression, preparation for FMT by use of proton pump inhibitor, antimotility agents and bowel lavage, previous recurrences, severity of CDI, antibiotic induction treatment, fresh or frozen FMT preparation, and route of application. Results: Treatment response was achieved in 191/240 evaluable cases (79.6%) at day 30 (D30) post FMT and 78.1% at day 90 (D90) post FMT. Assessment of clinical predictors for FMT failure by forward and confirmatory backward-stepwise regression analysis yielded higher age as an independent predictor of FMT failure (p = 0.001; OR 1.060; 95%CI 1.025-1.097). Conclusion: FMT in Germany is associated with high cure rates at D30 and D90. No specific pre-treatment, preparation or application strategy had an impact on FMT success. Only higher age was identified as an independent risk factor for treatment failure. Based on these and external findings, future studies should focus on the assessment of microbiota and microbiota-associated metabolites as factors determining FMT success.

Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial.

BACKGROUND: Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25-30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. METHODS: We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per µL, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 µg of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659. FINDINGS: Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1·84, 95% CI 0·86-3·91, p=0·12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. INTERPRETATION: Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D. FUNDING: The HepNet Study-House (a project of the German Liver Foundation founded by the German Liver Foundation, the German Ministry for Education and Research, and the German Center for Infectious Disease Research), Hoffmann-La Roche, and Gilead Sciences.

Endoscopic full-thickness resection for early colorectal cancer.

BACKGROUND AND AIMS: Current international guidelines recommend endoscopic resection for T1 colorectal cancer (CRC) with low-risk histology features and oncologic resection for those at high risk of lymphatic metastasis. Exact risk stratification is therefore crucial to avoid under-treatment as well as over-treatment. Endoscopic full-thickness resection (EFTR) has shown to be effective for treatment of non-lifting benign lesions. In this multicenter, retrospective study we aimed to evaluate efficacy, safety, and clinical value of EFTR for early CRC. METHODS: Records of 1234 patients undergoing EFTR for various indications at 96 centers were screened for eligibility. A total of 156 patients with histologic evidence of adenocarcinoma were identified. This cohort included 64 cases undergoing EFTR after incomplete resection of a malignant polyp (group 1) and 92 non-lifting lesions (group 2). Endpoints of the study were: technical success, R0-resection, adverse events, and successful discrimination of high-risk versus low-risk tumors. RESULTS: Technical success was achieved in 144 out of 156 (92.3%). Mean procedural time was 42 minutes. R0 resection was achieved in 112 of 156 (71.8%). Subgroup analysis showed a R0 resection rate of 87.5% in Group 1 and 60.9% in Group 2 (P < .001). Severe procedure-related adverse events were recorded in 3.9% of patients. Discrimination between high-risk versus low-risk tumor was successful in 155 of 156 cases (99.3%). In Group 1, 84.1% were identified as low-risk lesions, whereas 16.3% in group 2 had low-risk features. In total, 53 patients (34%) underwent oncologic resection due to high-risk features whereas 98 patients (62%) were followed endoscopically. CONCLUSIONS: In early colorectal cancer, EFTR is technically feasible and safe. It allows exact histological risk stratification and can avoid surgery for low-risk lesions. Prospective studies are required to further define indications for EFTR in malignant colorectal lesions and to evaluate long-term outcome.

Divergent strategies in pre- and postzygotic reproductive isolation between two closely related Dianthus species.

Quantifying the relative contribution of multiple isolation barriers to gene flow between recently diverged species is essential for understanding speciation processes. In parapatric populations, local adaptation is thought to be a major contributor to the evolution of reproductive isolation. However, extrinsic postzygotic barriers assessed in reciprocal transplant experiments are often neglected in empirical assessments of multiple isolation barriers. We analyzed multiple isolation barriers between two closely related species of the plant genus Dianthus, a genus characterized by the most rapid species diversification in plants reported so far. Although D. carthusianorum L. and D. sylvestris Wulf. can easily be hybridized in crossing experiments, natural hybrids are rare. We found that in parapatry, pollinator-mediated prezygotic reproductive isolation barriers are important for both D. carthusianorum (0.761) and D. sylvestris (0.468). In contrast to D. carthusianorum, high hybrid viability in D. sylvestris (-0.491) was counteracted by strong extrinsic postzygotic isolation (0.900). Our study highlights the importance of including reciprocal transplant experiments for documenting extrinsic postzygotic isolation and demonstrates clearly divergent strategies and hence asymmetric pre- and postzygotic reproductive isolation between closely related species. It also suggests that pollinator-mediated and ecological isolation could have interacted in synergistic ways, further stimulating rapid speciation in Dianthus.

[Conservative treatment of an aseptic abscess syndrome with splenic abscesses in Crohn's disease]. / Konservative Therapie eines aseptischen Abszesssyndroms mit Milzabszessen bei Morbus Crohn.

A 24-year old woman with a history of Crohn's disease developed bloody diarrhea and multiple abdominal abscesses, daily fever, leukocytosis, and elevated CRP several months after her immunosuppressive therapy with azathioprine was stopped. Recurrent abscess punctures did not detect any pathogenic germs and neither clinical nor serological response was achieved by administration of different antimicrobial therapies. Additionally, new splenic abscesses arose despite ongoing therapy. Under the suspicion of the rare aseptic abscess syndrome, representing an auto-inflammatory, extra-intestinal manifestation of Crohn's disease, the antimicrobial therapy was stopped and an intravenous therapy with prednisolone was initiated. As soon as therapeutic response was achieved, an additional anti-TNF therapy with Infliximab was started and subsequently the intraabdominal and splenic abscesses disappeared.The knowledge of the aseptic abscess syndrome, which is characterized by (a) sterile abscesses with neutrophilic granulocytes, (b) negative blood cultures, (c) lack of response to antimicrobial treatment, and (d) rapid clinical improvement after initiation of prednisolone therapy with subsequent response in imaging, may avoid unnecessary operations like splenectomy in the present case. The exact pathophysiology of the aseptic abscess syndrome is unknown but, with regard to the sterile aspirates, an auto-inflammatory cause has been suggested. Data of a French case collection demonstrate that this syndrome may be present more frequently than expected in patients with chronic inflammatory bowel diseases. Up to now, this syndrome has not been described in German literature.

Multimodal and sequential treatment improves survival in patients with hepatocellular carcinoma.

Background and aims Therapy of hepatocellular carcinoma (HCC) mainly depends on tumor stage and liver function. The aim of this study was to identify additional predictors of overall survival in HCC patients with a particular attention to multimodal therapies. Methods Six hundred and seven consecutive HCC-patients treated in a tertiary center between 1988 and 2011 were retrospectively analyzed. Multivariate analysis was performed by logistic and Cox-regression, overall survival was analyzed by Kaplan Meier statistics. Results In comparison to unimodal therapies, multimodal treatment increased overall survival in BCLC-A patients from 16 to 26 months (p < 0.001), in patients with BCLC-B stage from 9.5 to 16 months (p < 0.001), in BCLC-C patients from 6 to 18 months (p < 0.001), and in stage BCLC-D from 2 to 8 months (not significant). Survival increased throughout all Child Pugh scores, and patients experienced benefits from multimodal therapy irrespective of alfa-fetoprotein levels. Comparing the time span 1988 - 1999 with 2000 - 2011, the rate of multimodal/sequential treatment increased from 12.3 % to 30 % (p < 0.001), and the overall survival of all (treated and non-treated) patients increased from 7 months (1988 - 1999) to 10 months (2000 - 2011, p < 0.001). In multivariate analysis, multimodal treatment was shown to be an independent predictor for overall survival besides elevated alfa-fetoprotein, Child Pugh score, and BCLC stage. Conclusion Multimodal therapies increase overall survival in HCC patients and should be considered in patients with HCC if practicable.

Female butterflies adapt and allocate their progeny to the host-plant quality of their own larval experience.

Recent studies with diverse taxa have shown that parents can utilize their experience of the environment to adapt their offspring's phenotype to the same environmental conditions. Thus, offspring would then perform best under environmental conditions experienced by their parents due to transgenerational phenotypic plasticity. Such an effect has been dubbed transgenerational acclimatization. However, evidence that parents can subsequently ensure the appropriate environmental conditions in order that offspring benefit from transgenerational acclimatization has never been demonstrated. We reared Pieris rapae larvae in the parental generation on high-nitrogen and low-nitrogen host plants, and reared the offspring (F1) of both treatments again on high- and low-nitrogen plants. Furthermore, we tested if females prefer to oviposit on high- or low-nitrogen host plants in two-way choice tests. We here show not only that females adapt their offspring's phenotype to the host-plant quality that they themselves experienced, but that females also mainly oviposit on the host quality to which they adapt their offspring. Moreover, effects of larval host plant on oviposition preference of females increased across two generations in F1-females acclimatized to low-nitrogen host plants, showing an adaptive host shift from one generation to the next. These findings may have profound implications for host-race formation and sympatric speciation.

Transient Elastography for the Detection of Liver Damage in Patients with HIV.

INTRODUCTION: Highly active antiretroviral therapy (HAART) is effective and well tolerated, but hepatotoxicity is relatively common. Different non-invasive methods are available for detecting liver fibrosis in patients with chronic liver disease. METHODS: Patients who were HIV positive and who had given their informed consent were included in this cross-sectional study. Transient elastography [FibroScan(®) (FS); Echosens], serum hyaluronic acid (HA), Hepascore (HS), Fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were used to detect liver fibrosis in the patients. The agreement between FS and the other methods was evaluated. To observe the hepatotoxicity of HAART, patients with chronic viral hepatitis B or C were excluded by detection of hepatitis B surface antigens and hepatitis C virus antibodies. Patients with chronic alcohol intake were excluded by measuring carbohydrate-deficient transferrin (CDT). FS correlation with the duration of therapy with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) was evaluated. RESULTS: Overall, 203 patients were included in the study. The agreement between the different tests ranged from 64% to 77%: FS vs. HA, 72%; FS vs. APRI, 74%; FS vs. HS, 77%; and FS vs. FIB-4, 64%. After excluding patients with chronic hepatitis B or C and elevated CDT, 153 patients remained for studying the hepatotoxicity of HAART. A significant correlation of FS with the duration of medication intake was observed for PIs (P = 0.026; r = 0.18). NRTI and NNRTI therapy duration did not correlate with FS. CONCLUSIONS: The agreement between FS and other tests ranged from 64% to 77%. A significant correlation was found between liver stiffness and the duration of therapy with PIs, which underlines the known hepatotoxicity of this substance group. FUNDING: Heinz-Ansmann Foundation.

Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease.

BACKGROUND & AIMS: It is well known that inflammation increases liver stiffness (LS) in patients with chronic hepatitis C (HCV) and alcoholic liver disease (ALD) independent of fibrosis stage, but no inflammation-adapted cut-off values have been settled so far. An early identification of rapid fibrosers, however, is essential to decide whom to treat first with the novel but expensive antiviral drugs. METHODS: Liver stiffness, biopsy-proven fibrosis stages F0-F4 (METAVIR or Kleiner score) and routine laboratory parameters were studied in 2068 patients with HCV (n = 1391) and ALD (n = 677). RESULTS: Among the routine parameters for liver damage, AST correlated best with LS (HCV: r = 0.54, P < 0.0001 and ALD: r = 0.34, P < 0.0001). In the absence of elevated transaminases, cut-off values were almost identical between HCV and ALD for F1-2, F3 and F4 (HCV: 5.1, 9.0 and 11.9 kPa vs ALD: 4.9, 8.1 and 10.5 kPa). These cut-off values increased exponentially as a function of median AST level. The impact of AST on LS was higher in lobular-pronounced ALD as compared to portal tract-localized HCV. Most notably, Cohen's weighted Kappa displayed an improved agreement of the novel AST-dependent cut-off values with histological fibrosis stage both for HCV (0.68 vs 0.65) and ALD (0.80 vs 0.76). CONCLUSIONS: The novel AST-adapted cut-off values improve non-invasive fibrosis staging in HCV and ALD and may be also applied to other liver diseases. Especially in HCV, they could help to decide whom to treat first with the novel but expensive antiviral drugs.

Transient elastography improves detection of liver cirrhosis compared to routine screening tests.

AIM: To investigate the diagnostic significance of transient elastography (TE) in a daily routine clinical setting in comparison to clinical signs, laboratory parameters and ultrasound. METHODS: TE, ultrasound, laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine. RESULTS: Sensitivity of TE for the detection of liver cirrhosis was 90.4%, compared to 80.1% for ultrasound, 58.0% for platelet count and 45.1% for cutaneous liver signs (P < 0.0001 for comparisons with histology). AUROC for TE was 0.760 (95%CI: 0.694-0.825). Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825 (95%CI: 0.768-0.882). TE correlated with laboratory parameters of cirrhosis progression like albumin (r = -0.43), prothrombin time (r = -0.44), and bilirubin (r = 0.34; P < 0.001 for each). Particularly, in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1% (P < 0.04) and 16.3% (P < 0.02), respectively. CONCLUSION: Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.