High vaccination coverage and infection rate result in a robust SARS-CoV-2-specific immunity in the majority of liver cirrhosis and transplant patients: A single-center cross-sectional study.

BACKGROUND: In the third year of the SARS-CoV-2 pandemic, little is known about the vaccine- and infection-induced immune response in liver transplant recipients (LTR) and liver cirrhosis patients (LCP). OBJECTIVE: This cross-sectional study assessed the vaccination coverage, infection rate, and the resulting humoral and cellular SARS-CoV-2-specific immune responses in a cohort of LTR and LCP at the University Medical Center Hamburg-Eppendorf, Germany between March and May 2023. METHODS: Clinical and laboratory data from 244 consecutive patients (160 LTR and 84 LCP) were collected via chart review and a patient survey. Immune responses were determined via standard spike(S)- and nucleocapsid-protein serology and a spike-specific Interferon-gamma release assay (IGRA). RESULTS: On average, LTR and LCP were vaccinated 3.7 and 3.3 times, respectively and 59.4% of patients received ≥4 vaccinations. Altogether, 68.1% (109/160) of LTR and 70.2% (59/84) of LCP experienced a SARS-CoV-2 infection. Most infections occurred during the Omicron wave in 2022 after an average of 3.0 vaccinations. Overall, the hospitalization rate was low (<6%) in both groups. An average of 4.3 antigen contacts by vaccination and/or infection resulted in a seroconversion rate of 98.4%. However, 17.5% (28/160) of LTR and 8.3% (7/84) of LCP demonstrated only low anti-S titers (<1000 AU/ml), and 24.6% (16/65) of LTR and 20.4% (10/59) of LCP had negative or low IGRA responses. Patients with hybrid immunity (vaccination plus infection) elicited significantly higher anti-S titers compared with uninfected patients with the same number of spike antigen contacts. A total of 22.2% of patients refused additional booster vaccinations. CONCLUSION: By spring 2023, high vaccination coverage and infection rate have resulted in a robust, mostly hybrid, humoral and cellular immune response in most LTR and LCP. However, booster vaccinations with vaccines covering new variants seem advisable, especially in patients with low immune responses and risk factors for severe disease.

Stress fractures in systemic lupus erythematosus after long-term MTX use successfully treated by MTX discontinuation and individualized bone-specific therapy.

We report the case of a 64-year-old woman with systemic lupus erythematosus (SLE) and recurrent bilateral stress fractures of the calcaneus due to long-term methotrexate (MTX) use. A detailed skeletal assessment pointed to osteoporomalacia with pronounced trabecular thinning and increased bone resorption. After years of unsuccessful treatment with bisphosphonates, a combined bone-specific denosumab-teriparatide treatment was initiated, and additional belimumab treatment was started to avoid intermittent steroid usage. As these measures did not lead to a significant improvement of the bone situation, MTX was eventually discontinued. This was followed by a rapid clinical improvement. In a follow-up MRI scan after 18 months, the stress fractures had almost disappeared. Furthermore, the bone density and microarchitecture markedly improved. In conclusion, this case demonstrates that MTX discontinuation/replacement in combination with an individualized and state-of-the-art bone-specific therapy is effective in SLE patients with stress fractures after long-term MTX use.

Prospective comparison of diffusion-weighted MRI and dynamic Gd-EOB-DTPA-enhanced MRI for detection and staging of hepatic fibrosis in primary sclerosing cholangitis.

PURPOSE: To assess the diagnostic value of multiparametric magnetic resonance imaging (MRI) including dynamic Gd-EOB-DTPA-enhanced (DCE) and diffusion-weighted (DW) imaging for diagnosis and staging of hepatic fibrosis in primary sclerosing cholangitis (PSC) using transient elastography as a standard reference. MATERIAL AND METHODS: Multiparametric MRI was prospectively performed on a 3.0-Tesla scanner in 47 patients (age 43.9±14.3 years). Transient elastography derived liver stiffness measurements (LSM), DCE-MRI derived parameters (hepatocellular uptake rate (Ki), arterial (Fa), portal venous (Fv) and total (Ft) blood flow, mean transit time (MTT), and extracellular volume (Ve)) and the apparent diffusion coefficient (ADC) were calculated. Correlation and univariate analysis of variance with post hoc pairwise comparison were applied to test for differences between LSM derived fibrosis stages (F0/F1, F2/3, F4). ROC curve analysis was used as a performance measure. RESULTS: Both ADC and Ki correlated significantly with LSM (r= -0.614; p<0.001 and r= -0.368; p=0.01). The ADC significantly discriminated fibrosis stages F0/1 from F2/3 and F4 (p<0.001). Discrimination of F0/1 from F2/3 and F4 reached a sensitivity/specificity of 0.917/0.821 and 0.8/0.929, respectively. Despite significant inter-subject effect for classification of fibrosis stages, post hoc pairwise comparison was not significant for Ki (p>0.096 for F0/1 from F2/3 and F4). LSM, ADC and Ki were significantly associated with serum-based liver functional tests, disease duration and spleen volume. CONCLUSION: DW-MRI provides a higher diagnostic performance for detection of hepatic fibrosis and cirrhosis in PSC patients in comparison to Gd-EOB-DTPA-enhanced DCE-MRI. KEY POINTS: • Both ADC and hepatocellular uptake rate (Ki) correlate significantly with liver stiffness (r= -0.614; p<0.001 and r= -0.368; p=0.01). • The DCE-imaging derived quantitative parameter hepatocellular uptake rate (Ki) fails to discriminate pairwise intergroup differences of hepatic fibrosis (p>0.09). • DWI is preferable to DCE-imaging for discrimination of fibrosis stages F0/1 to F2/3 (p<0.001) and F4 (p<0.001).

Dynamic changes of circulating miRNAs induced by the Ebola virus vaccine VSV-EBOV.

VSV-EBOV is a replication-competent Ebola virus (EBOV) vaccine, which was tested in clinical trials as response to the Ebola virus disease (EVD) outbreak 2013-2016. It is the most advanced EBOV candidate currently in the licensure process. The experimental vaccine was again administered as response to outbreaks in the Democratic Republic of Congo. However, underlying molecular mechanisms that convey protection remain incompletely understood. MicroRNAs (miRNAs) are known key regulators that influence gene expression on a post-transcriptional level. The miRNA-mediated control has emerged as a critical regulatory principle in the immune system, which strongly influences the balance of innate and adaptive immune responses by modulation of signaling pathways critical for differentiation of immune cells. We investigated expression levels of circulating miRNAs (c-miRNAs) in plasma from healthy vaccinees, as they may reflect cellular dynamics following VSV-EBOV immunization and additionally may serve as potential biomarkers for vaccine efficacy. As part of the WHO-led VEBCON consortium, we investigated safety and immunogenicity of VSV-EBOV in a phase I trial. A comprehensive analysis of expression levels on c-miRNAs from plasma samples following VSV-EBOV immunization (day 0, 1, 3 post vaccination) was conducted using RT-qPCR assays. Potential biological relevance was assessed using in silico analyses. Additionally, we correlated dynamics of miRNA expressions with our previously reported data on vaccine-induced antibody and cytokine responses and finally evaluated the prognostic power by generating ROC curves. We identified four promising miRNAs (hsa-miR-146a, hsa-miR-126, hsa-miR-199a, hsa-miR-484), showing a strong association with adaptive immune responses, exhibited favourable prognostic performance and are implicated in immunology-related functions. Our results provide evidence that miRNAs may serve as useful biomarkers for prediction of vaccine-induced immunogenicity. Furthermore, our unique data set provides insight into molecular mechanisms that underlie VSV-EBOV-mediated protective immune responses, which may help to decipher VSV-EBOV immune signature and accelerate strategic vaccine design or personalized approaches.

Follow-up magnetic resonance imaging/3D-magnetic resonance cholangiopancreatography in patients with primary sclerosing cholangitis: challenging for experts to interpret.

BACKGROUND: In patients with primary sclerosing cholangitis follow-up magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is performed by many centres, particularly for the early detection of biliary malignancies and strictures. Clinically meaningful MRI-based definitions of primary sclerosing cholangitis related complications are, however, lacking. AIM: To investigate how primary sclerosing cholangitis experts interpret follow-up MRI/MRCP with a focus on conclusions that may impact clinical decision-making in primary sclerosing cholangitis. METHODS: Within the International Primary Sclerosing Cholangitis Study Group, an online survey on 16 real-life primary sclerosing cholangitis cases including clinical and biochemical information as well as a T2-weighted liver MRI/3D-MRCP was conducted. The interpretation of images and subsequent recommendations were assessed using a multiple-choice questionnaire. An inter-rater reliability calculation (Fleiss' kappa) was performed and factors potentially affecting the interpretation of magnetic resonance images were analysed using generalised linear mixed-effect models. RESULTS: Forty-four members/associates of the International Primary Sclerosing Cholangitis Study Group (median experience in the care of primary sclerosing cholangitis patients: 14 years) completed the survey. The MRI interpretation significantly varied among the participants. The lowest agreement was found with respect to the indication to perform subsequent endoscopic retrograde cholangiopancreatography (ERCP; Κ = 0.12, 95%CI 0.11-0.14). Elevated total bilirubin was the variable with the strongest effect on the rate of suspected dominant strictures, cholangiocarcinoma or ERCP recommendations. Liver cirrhosis did not prevent participants from recommending ERCP. Overall, the survey participants' recommendations contrasted the real-life management and outcome. CONCLUSIONS: In primary sclerosing cholangitis, the interpretation of follow-up MRI/3D-MRCP significantly varies even among experts and seems to be primarily affected by bilirubin levels. Generally accepted MRI-based definitions of primary sclerosing cholangitis-related complications are urgently needed.

Stabilisation of acute-on-chronic liver failure patients before liver transplantation predicts post-transplant survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe complication of liver cirrhosis associated with excess short-term mortality rates. Orthotopic liver transplantation (OLT) is a potentially life-saving therapeutic modality for acute-on-chronic liver failure patients, but selection of transplant candidates with an acceptable post-transplant outcome is difficult. AIM: To assess the risk of liver transplantation in patients with ACLF, and to determine parameters that predict post-transplant survival in this patient cohort. METHODS: We retrospectively analysed all 250 patients with cirrhosis who underwent their first liver transplantation between 2009 and 2014 at our institution, and assessed post-transplant outcomes. RESULTS: Of 250 cirrhotic liver transplant recipients, 98 patients fulfilled the diagnostic criteria for acute-on-chronic liver failure in the 3-month pre-transplant period. Compared to non-ACLF patients, ACLF was associated with significantly higher short-term morbidity and mortality after liver transplantation (90-day patient survival 96.1% non-ACLF vs 72.4% ACLF patients, P < 0.0001). Clinical improvement in the pre-transplant period, as defined by recovery of at least one previously failed organ system, was observed in 37 of 98 acute-on-chronic liver failure patients, mostly within several days after diagnosis. Most notably, clinical improvement prior to liver transplantation was associated with excellent post-transplant survival rates that approximated non-ACLF transplant recipients. Following the 90-day post-transplant period, patient survival and long-term graft functions were comparable between ACLF and non-ACLF liver transplant recipients for up to 5 years. CONCLUSIONS: Acute-on-chronic liver failure predicts adverse outcome after orthotopic liver transplantation. Given the dismal prognosis without transplantation, however, our results indicate that ACLF patients can be transplanted with comparably good outcomes, in particular patients who improve under conservative therapeutic measures.

Outcome and natural course of renal dysfunction in liver transplant recipients with severely impaired kidney function prior to transplantation.

BACKGROUND: Since introduction of the MELD score in the liver allograft allocation system, renal insufficiency has emerged as an increasing problem. Here we evaluated the course of kidney function in patients with advanced renal insufficiency prior to liver transplantation (LT). METHODS: A total of 254 patients undergoing LT at the University Medical Centre Hamburg-Eppendorf (2011-2015) were screened for renal impairment (GFR < 30 ml/min) prior to LT in this observational study. RESULTS: Eighty (32%) patients (median 60 years; M/F: 48/32) had significant renal impairment prior to LT. Median follow-up post-LT was 619 days. Patient survival at 90 days, one year and two years was 76%, 66% and 64%, respectively. Need for dialysis postoperatively but not preoperatively was associated with increased mortality (p < 0.05). Renal function improved in 75% of survivors, but 78% of patients had chronic kidney disease ≥ stage 3 at end of follow-up. Of eight (16%) survivors remaining on long-term dialysis, so far only four patients have received a kidney transplant. CONCLUSION: Postoperative dialysis affected long-term mortality. In 75% of survivors renal function improved, but still the majority of patients had an impaired renal function (CKD stage 3-5) at end of follow-up. Future studies should elucidate the impact of kidney dysfunction and dialysis on recipients' long-term survival.

Expert clinical management of autoimmune hepatitis in the real world.

BACKGROUND: High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based. AIM: To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH. METHODS: A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH. RESULTS: Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres. CONCLUSIONS: There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis.

Determinants and frequency of irritable bowel syndrome in a German sample.

BACKGROUND: To date there is no study that has estimated the prevalence of irritable bowel syndrome (IBS) in Germany according to the current Rome III criteria. The aim of the present study was to investigate the prevalence of IBS in a non-clinical German sample. Furthermore, we investigated the association of IBS with socio-demographic and psychological risk factors. METHODS: Baseline data from a prospective cohort study were analysed, including the IBS Module of the Rome III Diagnostic Questionnaires and validated psychometric scales including the Patient Health Questionnaire-15 (PHQ-15), the Big Five Inventory (BFI), the Perceived Stress Questionnaire (PSQ-5), and the Whiteley-Index (WI-7). The study population was compared to the German general population to appraise its representativeness. Multivariate logistic regression analyses were performed to identify possible risk factors associated with IBS. RESULTS: Between January 2011 and September 2012, 2419 persons participated (female 54.0 %, mean age 37.4 ±â€Š14.9 years). According to the Rome III criteria, 401 participants (16.6 %) suffered from IBS. Five predictors were independently associated with IBS: previous traveller's diarrhoea infection (OR = 1.76; 95 % CI = 1.34 to 2.31), higher somatic symptom burden (OR = 1.15; 95 % CI = 1.07 to 1.23), increased level of hypochondriasis (OR = 2.04; 95 % CI = 1.54 to 2.70), increased vulnerability to diarrhoea under stress (OR = 3.88; 95 % CI = 3.21 to 4.68) and perceived stress (OR = 1.43; 95 % CI = 1.04 to 1.99). CONCLUSIONS: Our analyses yielded a relatively high IBS prevalence estimate, compared to studies published more than ten years ago. This might partially be explained by the fact that the time criterion of the Rome III criteria (at least 3 days/month in last 3 months) is more inclusive compared to the time criterion of the Rome II criteria (at least 12 weeks, which need not be consecutive, in the preceding 12 months).

Efficacy and safety of sofosbuvir/ledipasvir for the treatment of patients with hepatitis C virus re-infection after liver transplantation.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with a particularly poor outcome after liver transplantation. In December 2014, sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) was approved for HCV genotype 1 and 4 in Europe. In orthotopic liver transplantation (OLT) recipients, the interferon-free treatment of HCV re-infection with novel direct-acting antivirals has been demonstrated to be safe and effective in clinical trials, but real-world data are missing. The aim of this study was to investigate the safety and efficacy of SOF/LDV FDC in OLT recipients in the real-life setting. METHODS: All consecutive OLT patients started on SOF/LDV FDC for 12 or 24 weeks at the University Medical Center Hamburg-Eppendorf and Medical School Hannover between October 2014 and August 2015 were retrospectively analyzed (n = 30). The primary efficacy endpoint was sustained virological response (SVR), i.e., absence of viremia 12 weeks after end of treatment (SVR 12). Liver function tests, creatinine, blood count, and HCV RNA (by polymerase chain reaction assay) were determined at each visit. RESULTS: SVR was achieved in 29/30 patients (96.67%) treated with SOF/LDV ± ribavirin (RBV) for 12 (n = 4) or 24 weeks (n = 25). Twenty-five patients (86.2%) received RBV. However, in 15 of the 25 patients, RBV administration had to be discontinued because of severe anemia (57.7%). One RBV-treated patient died of a myocardial infarction during antiviral therapy; this event was most likely not directly related to SOF/LDV. Aside from RBV-associated anemia, no severe side effects of the antiviral regimen were observed. CONCLUSION: Antiviral treatment with SOF/LDV is highly effective, safe, and well tolerated in OLT recipients. The addition of RBV often results in severe anemia, requiring dose reduction or discontinuation.

[Multiple abscesses after a cruise along the Latin American coast]. / Multiple Abszesse nach Südamerikakreuzfahrt.

We report a case of an extracutaneous involvement of pyoderma gangrenosum. The patient initially presented with multiple sterile abscesses of the skin, heart, prostate, and kidney. Extracutaneous involvement in pyoderma gangrenosum is very rare. Confirmation of the diagnosis was only possible after exclusion of other relevant differential diagnoses. Continuous search for microbes proved negative and after an empiric therapeutic attempt with prednisolone, the patient improved quickly. However, each time we reduced the steroids even in combination with methotrexate or with azathioprine the patient relapsed. Only after therapy with the tumor necrosis factor-α-inhibitor infliximab was permanent remission achieved.

Course of hepatitis C virus (HCV) RNA and HCV core antigen testing are predictors for reaching sustained virologic response in liver transplant recipients undergoing sofosbuvir treatment in a real-life setting.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with reduced graft survival in orthotopic liver transplant recipients. Treatment with the new direct-acting antivirals (DAAs) is safe and efficient, but no reliable predictive factors for sustained virologic response (SVR) have been identified so far. The HCV core antigen assay (HCV-core-Ag) is a new, inexpensive, and efficient method to detect viral antigens, but the value of this technique to predict treatment response in orthotopic liver transplantation (OLT) patients is still unclear. METHODS: All OLT patients who were treated with a sofosbuvir-based antiviral regimen at our center between March 2014 and August 2014 were included in the analysis (n = 20). HCV-core-Ag and HCV RNA (polymerase chain reaction [PCR]) were determined at each visit. Primary endpoints of this study were SVR at 4 or 12 weeks after end of treatment (SVR 4 and SVR 12). RESULTS: HCV-core-Ag tested negative after a median of 2 weeks (range 1-16 weeks) while PCR tests became negative after a median of 4 weeks (range 2-12 weeks). Time until PCR negativity and until HCV-core-Ag negativity showed a good correlation (R = 0.711, P < 0.001, Fig. ). Seventeen of 20 patients (85%) achieved SVR 12. SVR 12 was associated with a short time interval between treatment start and HCV PCR negativity (P = 0.005) or HCV-core-Ag negativity (P = 0.003, Mann-Whitney test). No severe side effects were observed. CONCLUSIONS: DAA treatment is safe and well tolerated in OLT. The time points of HCV-core-Ag loss and PCR negativity were predictors of SVR 12.

[Diagnostic workup and therapy of infectious diarrhea. Current standards]. / Diagnostik und Therapie infektiöser Durchfallerkrankungen. Was ist gesichert?

Infectious diarrhea is very common; its severity ranges from uncomplicated, self-limiting courses to potentially life-threatening disease. A rapid diagnostic workup providing detailed information on the suspected pathogen should be performed only in patients at risk, analyzing one single stool sample for Salmonella, Shigella, Campylobacter, and Norovirus. In the presence of risk factors, such as a history of antibiotic exposure within the last 3 months, testing for Clostridium difficile should be performed. Immunocompetent patients do not require specific antibiotic therapy. Exceptions exist in patients with severe comorbidities, immunodeficiency, fever/SIRS, and in patients with Shigella or C. difficile infection. Empirical antibiotic treatment should be considered in patients with fever and/or bloody diarrhea and in patients at risk. In patients with traveler's diarrhea, microbiological diagnosis is required only in patients with fever, bloody diarrhea, prolonged course of disease (more than 5 days), severe clinical course with hypotension or dehydration, and during outbreaks. In these patients one single fecal sample should be collected for stool cultures of Campylobacter, Shigella, and Salmonella, as well as microscopic examination for amoebiasis and Giardiasis. The main therapeutic measure for infectious diarrhea is sufficient oral rehydration. As in community-acquired diarrhea, azithromycin or ciprofloxacin are recommended-taking into account local antimicrobial resistance in the country of travel and possible side effects.

Comparison of autochthonous and imported cases of hepatitis A or hepatitis E.

BACKGROUND: Hepatitis A and hepatitis E are not limited to tropical countries but are also present in industrialized countries. Both infections share similar clinical features. There is no comparative study evaluating the clinical parameters of autochthonous and imported hepatitis A virus and hepatitis E virus infections. AIMS: The aim of this study was to determine differences between autochthonous and imported hepatitis A virus (HAV) and hepatitis E virus (HEV) infections. METHODS: Medical charts of all patients at our center with acute HAV and HEV infections were analyzed retrospectively (n = 50, study period 01/2009 - 08/2013). RESULTS: Peak bilirubin (median 8.6 vs. 4.4 mg/dL, p = 0.008) and ALT levels (median 2998 vs. 1666 IU/mL, p = 0.04) were higher in patients with hepatitis A compared to hepatitis E. In comparison to autochthones hepatitis E cases, patients with imported infections had significantly higher peak values for AST, ALT, bilirubin and INR (p = 0.009, p = 0.002, p = 0.04 and p = 0.049, respectively). In HAV infection, AST levels tended to be higher in imported infections (p = 0.08). CONCLUSIONS: (i) It is not possible to differentiate certainly between acute HAV and HEV infections by clinical or biochemical parameters, however, HAV infections might be associated with more cholestasis and higher ALT values. (ii) Imported HEV infections are associated with higher transaminases, INR and bilirubin levels compared to autochthonous cases and (iii) imported HAV infections tend to be associated with higher transaminases in comparison to autochthonous cases.

Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting.

The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case of chronic hepatitis E was observed in patients with normal liver enzymes, indicating that general screening of all OLT recipients is not necessary. However, if chronic hepatitis E develops, it can be treated efficiently with ribavirin.

[Economic burden of Clostridium difficile enterocolitis in German hospitals based on routine DRG data]. / Ökonomische Auswirkungen einer Clostridium-difficile-Enterokolitis in deutschen Krankenhäusern auf der Basis von DRG-Kostendaten.

BACKGROUND: Clostridium difficile associated diarrhea (CDAD) is not only a increasing medical but also economical problem. METHODS: Data from the DRG project group of the German society for digestive and metabolic diseases (DGVS) were analyzed for CDAD. Out of 430,875 cases from 37 German hospitals 2,767 cases were grouped by having CDAD either as primary (PD) or secondary diagnosis (SD; likely to be from a hospital source) in an initial or recurring hospital stay (RD). For comparison non-CDAD cases from the same hospitals from that year where matched using propensity score matching. As endpoints we defined LOS (length of stay), difference of LOS to national average LOS, total costs per case and difference between costs and revenue for all three groups. RESULTS: Patients from the PD group (n = 817) showed a mean LOS of 11.2 days compared to 8.5 days for the control group, 4,132 € mean cost per case (536 € more than control) and a mean loss of -1,064 € per case compared to -636 €. In the SD group (n = 1,840) patients stayed in the hospital for 28.8 days (control: 18.1 days), had costs of 19,381 € (control: 13,082 €) and a loss of -3,442 € compared to -849 € in the control group. Recurring cases (RD; n = 110) showed a LOS of 37.3 days (control: 21.3 days), had even higher costs (20.755 € vs. 13,101 €) and higher losses (-4,196 € vs. -1,109 €). CONCLUSION: By extrapolating these findings CDAD not only harms patients but generates a yearly cost burden of 464 million € for the German healthcare system including a loss of 197 million € for German hospitals. To the authors' opinion sufficient measures against CDAD should include pre hospital risk reduction programs, introduction of effective therapeutic and hygienic strategies in hospitals as well as improvements in documentation for these cases to support further developments of the German DRG system.