[Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective]. / Fäkaler Mikrobiota-Transfer (FMT) in Deutschland ­ Status und Perspektive.

INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.

Next Generation Sequencing Outperforms Cultivation-Based Methods for Detection of Bacterial Genera in Bile After Liver Transplantation.

Background and aims: Bacterial cholangitis is a common complication in patients with ischemic type biliary lesions and/or anastomotic strictures after liver transplantation (LTX). Patients frequently need antibiotics and endoscopic retrograde cholangiography (ERC) to improve the bile flow. Antibiotic treatment is based on findings in standard microbiological cultivation (SMC) of bile. However, the cultivation techniques are limited to a subset of bacteria easy-to-cultivate. Therefore, the aim of our study was to evaluate the value of next generation sequencing as an additional diagnostic tool to SMC in ischemic type biliary lesions and/or anastomotic strictures. Methods: We sequenced the V1-V2 region of the 16S rRNA gene in 242 stored bile samples in patients after LTX and compared the results with findings of SMC. SMC was performed in n = 135 (56%) fresh bile samples in addition to NGS. SMC was part of the clinical routine in these patients. Results: NGS detected bacterial genera in bile samples more often than SMC (P = 5.42 × 10-74). SMC showed insufficient discovery of bacterial genera compared to NGS with better performance in patients receiving antibiotics prior to ERC. SMC missed many bacterial genera detected by NGS. Conclusions: NGS was more sensitive in detecting bacteria in bile than SMC, no clinical parameters could be used to improve discovery rates in SMC and many genera were missed by SMC. Therefore, NGS should be used in a combined approach with SMC for improved diagnostics to achieve more specific and targeted antibiotic treatments.

Unique Metabolomic and Lipidomic Profile in Serum From Patients With Crohn's Disease and Ulcerative Colitis Compared With Healthy Control Individuals.

BACKGROUND: Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease. METHODS: Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale. RESULTS: Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2. CONCLUSIONS: Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.

The metabolic and lipidomic serum profile of patients with inflammatory bowel disease was analyzed using proton nuclear magnetic resonance spectroscopy. A significantly altered profile in comparison with healthy control individuals was identified, characterized by more atherogenic properties.

Cultivation-based characterization of biliary microbiota in bile samples collected during routine endoscopic retrograde cholangiography: 10 years of experience at a tertiary center.

INTRODUCTION: Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease. OBJECTIVES: To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease. METHODOLOGY: To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019. RESULTS: There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; n = 556), followed by patients with primary sclerosing cholangitis (PSC; n = 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P  < 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P  = 0.02, P  < 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P  < 0.001). CONCLUSION: Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future.

[A systematic analysis of nosocomial outbreaks of nosocomial infections after gastrointestinal endoscopy]. / Eine systematische Analyse nosokomialer Ausbrüche von Infektionskrankheiten in der gastrointestinalen Endoskopie.

Esophagogastroduodenoscopy (EGD), endoscopic retrograde cholangiopancreatography (ERCP) and colonoscopy (CLN) come with a potential risk of pathogen transmission. Unfortunately, up to now data on the causes and the distribution of pathogens is rather sparse.We performed a systematic review of the medical literature using the Worldwide Outbreak Database, the PubMed, and Embase. We then checked so-retrieved articles for potential sources of the outbreak, the spectrum of pathogens, the attack rates, mortality and infection control measures.In total 73 outbreaks (EGD: 24, ERCP: 42; CLN: 7) got included. The corresponding attack rates were 3.5%, 7.1% and 12.8% and mortality rates were 6.3%, 12.7% and 10.0% respectively. EGD was highly associated with transmission of enterobacteria including a large proportion of multi-drug resistant strains. ERCP led primarily to transmission of non-fermenting gram-negative rods. The most frequent cause was human failure during reprocessing regardless of the type of endoscope.Staff working in the field of endoscopy should always be aware of the possibility of pathogen transmission in order to detect and terminate those events at the early most time point. Furthermore, proper ongoing education of staff involved in the reprocessing and maintenance of endoscopes is crucial. Single-use devices may be an alternative option and lower the risk of pathogen transmission, but on the downside may also increase costs and waste.

Prospective study of computer-aided detection of colorectal adenomas in hospitalized patients.

BACKGROUND: Adenoma detection with polypectomy during total colonoscopy reduces the incidence of colorectal cancer (CRC) and colorectal cancer-associated mortality. The adenoma detection rate (ADR) is an established quality indicator, which is associated with a decreased risk for interval cancer. An increase in ADR could be demonstrated for several artificially intelligent, real-time computer-aided detection (CADe) systems in selected patients. Most studies concentrated on outpatient colonoscopies. This sector often lacks funds for applying costly innovations like CADe. Hospitals are more likely to implement CADe and information about the impact of CADe in the distinct patient cohort of hospitalized patients is scarce. METHODS: In this prospective, randomized-controlled study, we compared colonoscopies performed with or without computer-aided detection (CADe) system (GI Genius, Medtronic) performed at University Medical Center Schleswig-Holstein, Campus Luebeck. The primary endpoint was ADR. RESULTS: Overall, 232 patients were randomized with n = 122 patients in the CADe arm and n = 110 patients in the control arm. Median age was 66 years (interquartile range 51-77). Indication for colonoscopy was most often workup for gastrointestinal symptoms (88.4%) followed by screening, post-polypectomy and post-CRC surveillance (each 3.9%). Withdrawal time was significantly prolonged (11 vs. 10 min, p = 0.039), without clinical relevance. Complication rate was not different between the arms (0.8% vs. 4.5%; p = 0.072). The ADR was significantly increased in the CADe arm compared to the control (33.6% vs. 18.1%, p = 0.008). ADR increase was particularly strong for the detection in elderly patients aged ≥50 years (OR 6.3, 95% CI 1.7 - 23.1, p = 0.006). CONCLUSION: The use of CADe is safe and increases ADR in hospitalized patients.

The biliary microbiome in ischaemic-type biliary lesions can be shaped by stenting but is resilient to antibiotic treatment.

This study aims to characterize the biliary microbiome as neglected factor in patients with ischaemic-type biliary lesions (ITBL) after liver transplantation. Therefore, the V1-V2 region of the 16S rRNA gene was sequenced in 175 bile samples. Samples from patients with anastomotic strictures (AS) served as controls. Multivariate analysis and in silico metagenomics were applied cross-sectionally and longitudinally. The microbial community differed significantly between ITBL and AS in terms of alpha and beta diversity. Both, antibiotic treatment and stenting were associated independently with differences in the microbial community structure. In contrast to AS, in ITBL stenting was associated with pronounced differences in the biliary microbiome, whereas no differences associated with antibiotic treatment could be observed in ITBL contrasting the pronounced differences found in AS. Bacterial pathways involved in the production of antibacterial metabolites were increased in ITBL with antibiotic treatment. After liver transplantation, the biliary tract harbours a complex microbial community with significant differences between ITBL and AS. Fundamental changes in the microbial community in ITBL can be achieved with biliary stenting. However, the effect of antibiotic treatment in ITBL was minimal. Therefore, antibiotics should be administered wisely in order to reduce emerging resistance of the biliary microbiome towards external antibiotics.

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.

Microbiota-associated Risk Factors for Clostridioides difficile Acquisition in Hospitalized Patients: A Prospective, Multicentric Study.

BACKGROUND: Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on colonization with C. difficile are largely unavailable. METHODS: C. difficile status was assessed by GDH EIA and real-time PCR targeting the toxin A (tcdA) and B (tcdB) genes. 16S V3 and V4 gene sequencing results from fecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta diversity, LefSe, and the Piphillin functional inference approach to estimate functional capacity. RESULTS: 1506 patients were recruited into a prospective observational study (DRKS00005335) upon admission into one of five academic hospitals. 936 of them provided fecal samples on admission and at discharge and were thus available for longitudinal analysis. Upon hospital admission, 5.5% (83/1506) and 3.7% (56/1506) of patients were colonized with toxigenic (TCD) and non-toxigenic C. difficile (NTCD), respectively. During hospitalization, 1.7% (16/936) acquired TCD. Risk factors for acquisition of TCD included pre-existing lung diseases, lower GI endoscopy and antibiotics. Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococcus spp. Metagenomic pathway analysis identified steroid biosynthesis as the most underrepresented metabolic pathway in patients who later acquire C. difficile colonization. CONCLUSIONS: Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition. CLINICAL TRIALS REGISTRATION: DRKS00005335.

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.

Structured reporting of head and neck ultrasound examinations.

BACKGROUND: Reports of head and neck ultrasound examinations are frequently written by hand as free texts. Naturally, quality and structure of free text reports is variable, depending on the examiner's individual level of experience. Aim of the present study was to compare the quality of free text reports (FTR) and structured reports (SR) of head and neck ultrasound examinations. METHODS: Both standard FTRs and SRs of head and neck ultrasound examinations of 43 patients were acquired by nine independent examiners with comparable levels of experience. A template for structured reporting of head and neck ultrasound examinations was created using a web-based approach. FTRs and SRs were evaluated with regard to overall quality, completeness, required time to completion, and readability by four independent raters with different specializations (Paired Wilcoxon test, 95% CI) and inter-rater reliability was assessed (Fleiss' kappa). A questionnaire was used to compare FTRs vs. SRs with respect to user satisfaction (Mann-Whitney U test, 95% CI). RESULTS: By comparison, completeness scores of SRs were significantly higher than FTRs' completeness scores (94.4% vs. 45.6%, p < 0.001), and pathologies were described in more detail (91.1% vs. 54.5%, p < 0.001). Readability was significantly higher in all SRs when compared to FTRs (100% vs. 47.1%, p < 0.001). The mean time to complete a report, however, was significantly higher in SRs (176.5 vs. 107.3 s, p < 0.001). SRs achieved significantly higher user satisfaction ratings (VAS 8.87 vs. 1.41, p < 0.001) and a very high inter-rater reliability (Fleiss' kappa 0.92). CONCLUSIONS: As compared to FTRs, SRs of head and neck ultrasound examinations are more comprehensive and easier to understand. On the balance, the additional time needed for completing a SR is negligible. Also, SRs yield high inter-rater reliability and may be used for high-quality scientific data analyses.

Potential biomarkers to predict outcome of faecal microbiota transfer for recurrent Clostridioides difficile infection.

BACKGROUND & AIMS: Faecal microbiota transplantation (FMT) has proven high clinical efficacy in the management of recurrent Clostridioides difficile infection (rCDI) with cure rates of over 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain elusive. The aim of the present study was to investigate different potential predictors of response to FMT. METHODS: Faecal specimens of sixteen patients undergoing FMT for rCDI, as well as samples from the respective donors were collected and analyzed by 16S rRNA gene profiling, bile acid-inducible (baiCD) gene specific qPCR, and liquid chromatography tandem-mass spectrometry (LC-MS/MS) to quantify the concentrations of primary and secondary bile acids. RESULTS: Using the faecal concentration of the secondary bile acid lithocholic acid (LCA)within the patient specimens, we were able to predict response to FMT (accuracy 95.2%, sensitivity 100%, specificity 90.9%). By combining the faecal LCA concentration with the urinary pCS concentration, an accuracy of 100% was achieved. CONCLUSION: LCA appears to be a promising marker candidate for prediction of clinical response to FMT. Other makers, such as urinary concentration of pCS, but not 3-IS, might be used to improve accuracy of prediction. Further studies are warranted to validate these candidate markers.

Tuberculosis Specific Interferon-Gamma Production in a Current Refugee Cohort in Western Europe.

BACKGROUND: In 2015, a high number of refugees with largely unknown health statuses immigrated to Western Europe. To improve caretaking strategies, we assessed the prevalence of latent tuberculosis infection (LTBI) in a refugee cohort. METHODS: Interferon-Gamma release assays (IGRA, Quantiferon) were performed in n = 232 inhabitants of four German refugee centers in the summer of 2015. RESULTS: Most refugees were young, male adults. Overall, IGRA testing was positive in 17.9% (95% CI = 13.2⁻23.5%) of subjects. Positivity rates increased with age (0% <18 years versus 46.2% >50 years). Age was the only factor significantly associated with a positive IGRA in multiple regression analysis including gender, C reactive protein, hemoglobin, leukocyte, and thrombocyte count and lymphocyte, monocyte, neutrophil, basophil, and eosinophil fraction. For one year change in age, the odds are expected to be 1.06 times larger, holding all other variables constant (p = 0.015). CONCLUSION: Observed LTBI frequencies are lower than previously reported in similar refugee cohorts. However, as elderly people are at higher risk for developing active tuberculosis, the observed high rate of LTBI in senior refugees emphasizes the need for new policies on the detection and treatment regimens in this group.

Automated low-flow ascites pump in a real-world setting: complications and outcomes.

BACKGROUND AND AIMS: The aim of this study was to investigate the Alfapump, an automated low-flow pump system for the treatment of refractory ascites (RA) as an alternative for repeated large-volume paracentesis in patients with contraindication for placement of a transjugular intrahepatic portosystemic shunt (TIPS) or liver transplantation. MATERIALS AND METHODS: In 21 consecutive patients with RA and contraindication for a placement of a TIPS, the Alfapump was implanted at Hannover Medical School between December 2012 and May 2016. Repeated laboratory, clinical, and microbiology data were collected and analyzed to assess the outcome of patients with an Alfapump. Half of the patients received a modified peritoneal catheter. RESULTS: Twenty-one patients with RA in end-stage liver disease and with a contraindication to TIPS placement received the Alfapump. Diuretic dosages were significantly reduced, and the number of paracentesis declined from 2.3±2.7 to 0 per week. Using the Alfapump, kidney function and serum sodium remained stable. Likewise, serum albumin remained stable in the absence of albumin infusions. Thirty-three complications (dislocation and/or blockade of the catheter, infection, pump dysfunction) related to the Alfapump were observed in 15 of 21 patients (71.4%), and 21 surgical interventions were needed in 15 patients (71.4%, 1-3 interventions per patient). A new peritoneal catheter system could significantly reduce blockage of the peritoneal catheter. CONCLUSION: The Alfapump is an effective treatment in patients with RA. However, a high rate of complications were observed, which could be reduced with a modified peritoneal catheter.

BaiCD gene cluster abundance is negatively correlated with Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7α-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon in C. scindens as well as in C. hiranonis, two Clostridium sp. recently reported to protect against C. difficile colonization. AIM: To analyze baiCD gene abundance in C. difficile positive and negative fecal samples. MATERIAL & METHODS: A species-specific qPCR for detecting baiCD genes was established. Fecal samples of patients with CDI, asymptomatic toxigenic C. difficile colonization (TCD), non-toxigenic C. difficile colonization (NTCD), of C. difficile negative (NC) patients, and of two patients before and after fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) were tested for the presence of the baiCD genes. RESULTS: The prevalence of the baiCD gene cluster was significantly higher in C. difficile negative fecal samples than in samples of patients diagnosed with CDI (72.5% (100/138) vs. 35.9% (23/64; p<0.0001). No differences in baiCD gene cluster prevalence were seen between NC and NTCD or NC and TCD samples. Both rCDI patients were baiCD-negative at baseline, but one of the two patients turned positive after successful FMT from a baiCD-positive donor. CONCLUSION: Fecal samples of CDI patients are less frequently baiCD-positive than samples from asymptomatic carriers or C. difficile-negative individuals. Furthermore, we present a case of baiCD positivity observed after successful FMT for rCDI.

Real-world effect of ribavirin on quality of life in HCV-infected patients receiving interferon-free treatment.

BACKGROUND & AIMS: Ribavirin (RBV) is commonly used for the treatment of hepatitis C virus (HCV) infection. However, RBV is associated with a reduced quality of life (QOL). We aim to assess the impact of RBV on QOL in a real-world setting. METHODS: In a prospective study, QOL was measured by a SF-36 questionnaire in 174 patients. In all, 85 patients were treated with RBV and 89 patients without RBV. QOL was assessed at baseline, week 12 of treatment and 24 weeks after treatment. RESULTS: Patients treated with RBV were more likely to have HCV genotype 2 and 3 infection and cirrhosis (all P < .05). RBV-treated patients reported lower scores for several domains of QOL already at baseline. During HCV treatment, RBV-free treatment led to an increase in all measured dimensions of quality of life, whereas RBV treatment led to a decrease in the emotional and physical functioning. After treatment, all dimensions for QOL showed improvement across the study cohort, regardless whether RBV was part of the treatment regimen. However, 28.8%-45.2% of treated patients perceive a sustained reduction in their physical or mental capacity after treatment, not related to RBV usage or SVR, but related to older age (P = .03) and cirrhosis (P = .02). CONCLUSIONS: During treatment, RBV leads to a reduced QOL, whereas RBV-free treatment leads to an increased QOL. After treatment, QOL strongly increases in both, RBV and RBV-free treated patients. Some patients perceive a sustained reduction in QOL, which seems unrelated to treatment.

Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls.

BACKGROUND & AIMS: The importance of the intestinal microbiota for the onset and clinical course of many diseases, including liver diseases like non-alcoholic steatohepatitis and cirrhosis, is increasingly recognized. However, the role of intestinal microbiota in chronic hepatitis C virus (HCV) infection remains unclear. METHODS: In a cross-sectional approach, the intestinal microbiota of 95 patients chronically infected with HCV (n=57 without cirrhosis [NO-CIR]; n=38 with cirrhosis [CIR]) and 50 healthy controls (HC) without documented liver diseases was analysed. RESULTS: Alpha diversity, measured by number of phylotypes (S) and Shannon diversity index (H'), decreased significantly from HC to NO-CIR to CIR. S and H' correlated negatively with liver elastography. Analysis of similarities revealed highly statistically significant differences in the microbial communities between HC, NO-CIR and CIR (R=.090; P<1.0×10-6 ). Stratifying for HCV genotypes even increased the differences. In addition, we observed distinct patterns in the relative abundance of genera being either positive or negative correlated with diseases status. CONCLUSIONS: This study shows that not only the stage of liver disease but also HCV infection is associated with a reduced alpha diversity and different microbial community patterns. These differences might be caused by direct interactions between HCV and the microbiota or indirect interactions facilitated by the immune system.