Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice.

Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-APOE4 knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2 months. At 24 months of age, the redox/immunologic status was evaluated by flow cytometry/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68+ microglia (brain) and CD8+ T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII+ microglia and CD11b+CD4+ T cells (brain) and (2) higher CD11b+CD4+ T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.

Performance, health, and physiological responses of newly received feedlot cattle supplemented with pre- and probiotic ingredients.

Nutritional strategies that optimize immunity of feedlot cattle are warranted due to increasing regulations with the use of feed-grade antimicrobials. This study evaluated physiological, health, and performance responses of cattle receiving a synbiotic supplement (yeast-derived prebiotic + Bacillus subtilis probiotic), which replaced feed-grade antimicrobials or were fed in conjunction with monensin during the initial 45 days in the feedlot. Angus-influenced steers (n = 256) were acquired from an auction facility on day -2, and transported (800 km) to the feedlot. Shrunk BW was recorded upon arrival (day -1). Steers were allocated to 1 of 18 pens (day 0), and pens were assigned to receive (n = 6/treatment) a free-choice diet containing: (1) monensin and tylosin (RT; 360 mg/steer daily from Rumensin and 90 mg/steer daily from Tylan; Elanco Animal Health, Greenfield, IN, USA), (2) yeast-derived ingredient and B. subtilis probiotic (CC; 18 g/steer daily of Celmanax and 28 g/steer daily of Certillus; Church and Dwight Co., Inc., Princeton, NJ, USA), or (3) monensin in addition to yeast-derived and B. subtilis ingredients (RCC) as in RT and CC. Steers were assessed for bovine respiratory disease (BRD) and DMI daily. Steer BW was recorded on days 45 and 46, and averaged for final BW. Blood samples were collected on days 0, 7, 17, 31, and 45. Feed intake was greater (P ≤ 0.05) in CC vs. RCC and RT during the initial 3 weeks upon feedlot arrival. No treatment differences were noted (P ≥ 0.41) for average daily gain, BW, and feed efficiency. Incidence of BRD did not differ (P = 0.77) between treatments (average 80.1%). A greater proportion (P ≤ 0.03) of RT steers diagnosed with BRD required a second antimicrobial treatment compared with CC and RCC (57.3, 37.3, and 38.6%, respectively). Removal of steers from the trial due to severe morbidity + mortality was greater (P = 0.02) in RT vs. CC (22.4 and 7.0%), and did not differ (P ≥ 0.16) among RCC (12.9%) vs. RT and CC. Plasma glucose concentrations were greater (P ≤ 0.02) in CC vs. RCC and RT on day 7. Plasma concentrations of nonesterified fatty acids were greater (P ≤ 0.02) in RT and RCC vs. CC on day 7, and in RT vs. CC on day 17. Steers receiving the synbiotic supplement had improved response to BRD treatment, suggesting heightened immunocompetence from partially enhanced metabolism and the nutraceutical effects of B. subtilis and yeast compounds.

Modalities and accuracy of diagnosis of external ventricular drainage-related infections: a prospective multicentre observational cohort study.

BACKGROUND: Device infection is a major complication of placement external ventricular drains (EVD). Diagnostic features are often masked by underlying disease or cerebrospinal fluid (CSF) contamination by blood. We aim to assess which diagnostic modalities are applied for EVD-related infection (ERI) diagnosis and evaluate their accuracy. METHODS: This observational prospective study included 187 adult patients with an EVD. Modalities of clinical diagnosis of ERI diagnosed by treating physicians on clinical grounds and blood and CSF analysis (clinically diagnosed ERI (CD-ERI)) were assessed prospectively. Additionally, the diagnostic accuracy of clinical and laboratory parameters for the diagnosis of culture proven ERI (CP-ERI) was evaluated, using data of the study patients and including a retrospective cohort of 39 patients with CP-ERI. RESULTS: Thirty-one CD-ERIs were diagnosed in the prospective cohort. Most physicians used CSF analysis to establish the diagnosis. ROC analysis revealed an AUC of 0.575 (p = 0.0047) for the number of positive SIRS criteria and AUC of 0.5420 (p = 0.11) for the number of pathological neurological signs for diagnosis of CP-ERI. Diagnostic accuracy of laboratory values was AUC 0.596 (p = 0.0006) for serum white blood cell count (WBCC), AUC 0.550 (p = 0.2489) for serum C-reactive protein, AUC 0.644 (p < 0.0001) for CSF WBCC and AUC 0.690 for CSF WBC/red blood cell count ratio (both p < 0.0001). Neither a temporal trend in potential predictors of CP-ERI nor a correlation between clinical diagnosis and proven CSF infection was found. CONCLUSIONS: Clinicians base their diagnosis of ERI mostly on CSF analysis and occurrence of fever, leading to over-diagnosis. The accuracy of the clinical diagnosis is low. Commonly used clinical and laboratory diagnostic criteria have a low sensitivity and specificity for ERI.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Highly anisotropic electric conductivity in PAN-based carbon nanofibers.

In addition to the chemical and physical properties of nanostructures their successful utilization for applications is strongly triggered by economic aspects. Electrospinning of nanowires from solution followed by subsequent annealing steps is a comparably cheap technique to fabricate conductive carbon nanofibers (CNF) made from polyacrylonitrile (PAN) molecules in large quantities. In this work, we investigated the microscopic properties of the CNFs with diameters of 100-300 nm by means of Raman and x-ray photoelectron spectroscopy and correlated these results with transport measurements done with a 4-tip STM. In particular, we investigated the effect of fiber alignment and knot densities, which can be controlled by applying constant creep due to stress during the stabilization process. The comparison of the conductivity obtained from single CNFs revealed further that the fiber crossings within the ensemble structure act as scattering centers and proofs that the transport is along the surfaces of the CNFs.

HBsAg and anti-HCV screening in elderly hospitalized patients of a German tertiary referral centre.

BACKGROUND: Elderly patients are under-represented in hepatitis B and C screening approaches, but may be at increased risk for advanced liver disease. We therefore screened a hospitalized elderly population. MATERIALS AND METHODS: 6011 admissions to the department of internal medicine and neurology within one year were screened for HBsAg and anti-HCV (Elecsys(®)-HBsAg and -anti-HCV). Positive anti-HCV results were confirmed with the INNO-LIA™ assay. HCV-RNA was analyzed by real-time PCR in the case of confirmed positive anti-HCV results, HBV-DNA in the confirmed HBsAg positive individuals. RESULTS: Patient´s mean age (62.4 years) was 19 years above that of the average German population. The confirmed HBsAg prevalence was 0.6 %. 34 % (n = 12/35) of HBsAg positive cases were newly diagnosed, three of them presented with HBV-DNA levels > 2000 IU/mL. The confirmed anti-HCV prevalence was 0.9 %. 14 % (n = 8/56) of anti-HCV positive patients were previously undiagnosed. HCV-RNA was positive in three of them. In newly diagnosed individuals cirrhosis was present in 1/12 of the HBsAg and in 3/8 of the anti-HCV positive individuals. Compared to non-infected controls, the following risk factors were significantly more frequent in infected patients: (i) HBsAg: sexual exposure (20 % vs. 2 %), blood transfusion before 1992 (13 % vs. 6 %), referrals from nursing homes (10 % vs. 1 %). (ii) Anti-HCV: blood transfusion before 1992 (41 % vs. 6 %), IVDU (25 % vs. 0.5 %), organ transplantation (20 % vs. 5 %), hemodialysis (11 % vs. 3 %). CONCLUSIONS: HBsAg and anti-HCV were underdiagnosed in a senescent population, however, only few cases presented with advanced liver disease. Referrals from nursing homes were at increased risk for HBV infection.

The impact of docetaxel-related toxicities on health-related quality of life in patients with metastatic cancer (QoliTax).

BACKGROUND: Docetaxel is a widely used cytotoxic agent. This study evaluates the impact of docetaxel toxicities on patient's health-related quality of life (QoL). PATIENTS AND METHODS: We conducted a multicenter, prospective, non-interventional trial, in which the QoL was assessed using the EORTC QLQ-C30 questionnaires at baseline and every 4 weeks up to 40 weeks in patients receiving a docetaxel-based chemotherapy for metastatic disease. Treatment-related adverse events were correlated with the corresponding QoL scores. Uni- and multivariate analyses were applied. RESULTS: From January 2008 to June 2011, a total of 2659 patients were included. The majority of patients (48.1%) had prostate cancer, followed by breast (17.1%) and non-small-cell-lung cancer (15.8%). Patients received a median of 5 docetaxel cycles with the median dose of 75 mg/m(2). The presence of grade 3/4 diarrhea showed the strongest effect on global health status/QoL average scores (50.91 versus 33.06), followed by vomiting (50.91 versus 35.17), dyspnea (50.94 versus 35.81), mucositis/stomatitis (50.88 versus 36.41), nausea (50.91 versus 36.68), infection (50.90 versus 37.14), fatigue (50.90 versus 43.82) and anemia (50.91 versus 41.03), P < 0.05 for all comparisons. Grade 3/4 leukopenia/neutropenia, alopecia, constipation, neurotoxicity and nail disorders had no significant impact on the global health status/QoL or other items. CONCLUSION: In this large non-interventional trial, docetaxel-associated grade 3 or 4 toxicities were shown to have a strong detrimental effect on patient's QoL. Notably, diarrhea and vomiting had the strongest negative impact on QoL measures. This has to be kept in mind while making therapeutic decisions and providing optimized supportive treatment measures. CLINICAL TRIALS NUMBER: This study was registered at Deutsches Krebsstudienregister (DKSR, primary registry in the WHO Registry Network) with the ID 527.

Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 µm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 µm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 µm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

Gender differences in patient receiving liver transplantation for viral hepatitis.

INTRODUCTION: The course of viral hepatitis shows wide interindividual differences, ranging from asymptomatic disease to liver failure. Only limited data on gender differences in patients undergoing liver transplantation (OLT) exist. We studied the gender distribution in patients who underwent liver transplantation for viral hepatitis. METHODS: A retrospective analysis was performed on a cohort of 368 patients who underwent OLT for viral hepatitis-associated acute or chronic liver failure. In 96 of them, additional hepatocellular carcinoma (HCC) was present at transplantation. Gender ratios of the different hepatitis virus infections and in relation to HCC were evaluated. RESULTS: Significantly more males than females underwent OLT for chronic HBV. In contrast, patients after OLT for fulminant HBV were more frequently females. In patients transplanted for chronic HCV or HDV, no significant gender differences were found. However, men presented more frequently with HCC in both groups of chronic liver disease. CONCLUSIONS: There was a gender difference in HBV infection with more women developing fulminant hepatic failure in acute HBV while more men progressed to end-stage liver disease in chronic HBV. The role of gender in chronic HCV and HDV infection was less pronounced, except for a male predominance among patients with HCC.

Different patterns of decompensation in patients with alcoholic vs. non-alcoholic liver cirrhosis.

BACKGROUND: The histological pattern of fibrosis in liver cirrhosis varies in different chronic liver diseases, and hepatic decompensation may be differentiated in consequences of fibrosis (i.e. ascites, variceal bleeding) or in lack of function (i.e. jaundice) resulting in aetiology-specific variable morbidity and mortality. AIM: To evaluate patterns of hepatic decompensation in relation to the aetiology of liver cirrhosis. METHODS: Two different cohorts were retrospectively evaluated between 2002 and 2007. Cohort A was for hypothesis generation and consisted of 220 cirrhotic patients. To confirm the initial observations a second cohort B (n = 217) was analysed. The different patterns of hepatic decompensation evaluated were ascites, jaundice, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome or hepatocellular carcinoma. Furthermore, we analysed survival in relation to pattern of decompensation in alcoholic vs. non-alcoholic liver disease. RESULTS: Alcoholics were more frequently hospitalised for ascites (cohort A: 81.4% vs. 65.4%, P = 0.016; cohort B 71.3% vs. 58.5%, P = 0.085). In contrast, non-alcoholics presented with higher rates of hepatocellular carcinoma (cohort A: 23.1% vs. 11.9%, P = 0.046; cohort B 38.6% vs. 22.5%, P = 0.018). There were no significant differences in jaundice, variceal bleeding, hepatorenal syndrome or encephalopathy. Survival was significantly impaired in non-alcoholic cirrhosis once ascites occurred (P = 0.003), whereas ascites did not predict higher mortality in patients with alcoholic cirrhosis. CONCLUSIONS: Ascites is the leading initial pattern of decompensation in alcoholic cirrhosis whereas hepatocellular carcinoma dominates in non-alcoholics. Non-alcoholics developing ascites show a poor survival.

Quantification of HBsAg and HBV-DNA during therapy with peginterferon alpha-2b plus lamivudine and peginterferon alpha-2b alone in a German chronic hepatitis B cohort.

BACKGROUND: Peginterferon alpha-2b (PEG-IFNa2b) and lamivudine are efficient treatment options for chronic hepatitis B virus (HBV) infection. We assumed that a combination therapy of PEG-IFNα-2b plus lamivudine will be more effective than PEG-IFNα-2b alone concerning loss of HBV-DNA, HBeAg seroconversion, and HBsAg reduction. PATIENTS AND METHODS: Patients with chronic hepatitis B were randomised to nine months treatment with PEG-IFNα-2b 1.5 µg/kg o. i. w. or PEG- IFNα-2b plus lamivudine 100 mg/d. The study was designed with 60 patients per treatment arm. The primary endpoint was defined as loss of HBV-DNA (< 400 copies/mL) 24 weeks after the end of therapy. HBV-DNA (PCR), HBsAg (Architect, Abbott), and HBeAg (Axsym, Abbott) were determined prior to and at the end of treatment as well as at follow-up. HBV-genotypes were determined by Innolipa (Innogenetics). RESULTS: Only 32 patients were randomised to combination therapy and 27 individuals to monotherapy due to low recruitment rates. On treatment reduction of HBV-DNA was significantly higher during combination therapy compared to PEG-IFNa-2b monotherapy (- 4.60 ± 2.71 vs. - 2.41 ± 2.17 log; p = 0.003). However, there was no difference in the number of cases achieving HBV-DNA < 400 copies/mL, ALT normalisation, or HBeAg seroconversion at follow-up. None of the parameters was significantly related to HBV-genotypes. In a post-hoc analysis serum HBsAg levels were analysed as an additional prognostic parameter for treatment response (n = 29). Combination therapy showed a stronger, but not significant HBsAg decline during (- 0.7 ± 1.17 log IU/mL vs. - 0.26 ± 0.61 log IU/mL; p = 0.35) and after therapy (- 0.68 ± 1.29 log IU/mL vs. - 0.24 ± 0.56 log IU/mL; p = 0.82). Two of three cases with a 2-log HBsAg decline to HBsAg levels < 100 IU/mL eliminated HBsAg during long-term follow-up. CONCLUSION: The study was underpowered with respect to the primary endpoint due to low recruitment rates. However, in the post-hoc analysis HBsAg decline was over two-fold stronger at the end of treatment and follow-up after combination therapy and did not rebound after lamivudine withdrawal. These results may indicate the usefulness of future combination therapies without discontinuation of nucleos(t)ide analogues.

Quality management in the prophylaxis of venous thrombembolism--results of a survey including 464 medical and surgical patients.

BACKGROUND: We surveyed the quality of risk stratification politics and monitored the rate of entries to our company-wide protocol for venous thrombembolism (VTE) prophylaxis in order to identify safety concerns. PATIENTS AND METHODS: Audit in 464 medical and surgical patients to evaluate quality of VTE prophylaxis. RESULTS: Patients were classified as low 146 (31 %), medium 101 (22 %), and high risk cases 217 (47 %). Of these 262 (56.5 %) were treated according to their risk status and in accordance with our protocol, while 9 more patients were treated according to their risk status but off-protocol. Overtreatment was identified in 73 (15.7 %), undertreatment in 120 (25,9 %) of all patients. The rate of incorrect prophylaxis was significantly different between the risk categories, with more patients of the high-risk group receiving inadequate medical prophylaxis (data not shown; p = 0.038). Renal function was analyzed in 392 (84.5 %) patients. In those patients with known renal function 26 (6.6 %) received improper medical prophylaxis. If cases were added in whom prophylaxis was started without previous creatinine control, renal function was not correctly taken into account in 49 (10.6 %) of all patients. Moreover, deterioration of renal function was not excluded within one week in 78 patients (16.8 %) and blood count was not re-checked in 45 (9.7 %) of all patients after one week. There were more overtreatments in surgical (n = 53/278) and more undertreatments in medical patients (n = 54/186) (p = 0.04). Surgeons neglected renal function and blood controls significantly more often than medical doctors (p-values for both < 0.05). CONCLUSIONS: We found a low adherence with our protocol and substantial over- and undertreatment in VTE prophylaxis. Besides, we identified disregarding of renal function and safety laboratory examinations as additional safety concerns. To identify safety problems associated with medical VTE prophylaxis and "hot spots" quality management-audits proved to be valuable instruments.

Acoustic radiation force impulse (ARFI) elastography in acute liver failure: necrosis mimics cirrhosis.

Acoustic radiation force Impulse (ARFI) technology correlates shear-wave velocity with fibrosis. It can differentiate between advanced fibrosis and normal tissue in chronic liver disease. However, specificity is impaired by cholestasis, inflammation or oedema in acute hepatitis. In patients with acute liver failure (ALF) necessitating liver transplantation ARFI has not been evaluated yet. We investigated 3 patients with ALF and compared their ARFI results to those of healthy controls (n = 33) and cases with liver cirrhosis (n = 21). In the 3 ALF patients shear-wave velocities were 3.0, 2.5, and 2.7 m/s, respectively. These results were significantly increased compared to those of healthy controls (median: 1.13 m/s; p < 0.001) and similar to those of cirrhotic individuals (median: 2.93 m/s). Two individuals underwent liver transplantation. Explants showed massive necrosis, but no signs of chronic liver disease. Patient 3 recovered spontaneously and showed decreasing ARFI results during follow-up. In conclusion, hepatic necrosis can mimic liver cirrhosis at ARFI evaluation in ALF patients and this impairs the specificity of ARFI.

Quality of life in patients with various liver diseases: patients with HCV show greater mental impairment, while patients with PBC have greater physical impairment.

Little is known comparing and contrasting quality of life (QoL) in patients with hepatitis C, compared to patients with other liver diseases. We performed two independent prospective cross-sectional studies including 511 and 284 patients with different forms of liver diseases. SF-36 was used in both studies. Fatigue Impact Score, WHO-BREF and Hospital Anxiety and Depression Scale (HADS) were used in either study only. In both studies, HCV-positive patients scored worse in the mental aspects of health-related QoL compared to other liver diseases, except for HBV in one study. Surprisingly, in both studies, quality of life was also significantly impaired in patients with viral clearance after interferon therapy but not after spontaneous clearance. Furthermore, patients with primary biliary cirrhosis showed significantly better mental health but significantly worse physical well-being. Liver diseases differ in their form of impaired QoL. In HCV, this impairment might not always return to normal after treatment-induced viral clearance. This may suggest that HCV either may not be involved in QoL impairment or may induce a process which persists after viral clearance in some patients.

Prevention of lamivudine-resistant hepatitis B recurrence after liver transplantation with entecavir plus tenofovir combination therapy and perioperative hepatitis B immunoglobulin only.

Combination therapy with antivirals plus hepatitis B immunoglobulin (HBIg) has become the standard treatment for prevention of post-liver transplant hepatitis B virus (HBV) recurrence. However, HBIg therapy is inconvenient and expensive. Alternative therapeutic approaches with modern nucleos(t)ide analogues are limited so far. The present case report describes prevention of HBV recurrence with entecavir and tenofovir. A 48-year-old male patient with hepatitis B-induced decompensated liver cirrhosis initially improved on lamivudine (LAM) until LAM resistance (rtL180M and rtM204V) emerged followed by renewed decompensation. Therefore, tenofovir was added to LAM leading to undetectable HBV DNA (<200 copies/mL). Six months later, low-level viremia (479 copies/mL) was detected. Treatment was escalated to tenofovir plus entecavir. HBV DNA became negative again, and the patient underwent orthotopic liver transplantation. HBIg was administered during transplantation (10,000 IU) and on the second and third postoperative days (total dose 26,000 IU). Subsequently, the anti-hepatitis B surface (HBs) titer rose to 1477 IU/L at day 4 post transplantation. Although HBIg should have been continued, the patient remained on combination therapy with tenofovir plus entecavir only. The anti-HBs titer decreased and became negative 4 months later. However, under continued combination therapy with oral antivirals, HBV DNA and hepatitis B surface antigen remained negative during the entire follow-up of 21 months after liver transplantation. Combination therapy with entecavir plus tenofovir may prevent post-liver transplant hepatitis B recurrence even without HBIg maintenance therapy. This case illustrates that combination oral antiviral therapy might substitute for HBIg as indefinite prophylactic regimen due to profound antiviral efficacy and low risk of viral resistance. Efficacy and safety must be further investigated in randomized controlled trials.

Resistance management in chronic hepatitis B complicated by renal failure.

Therapy of chronic hepatitis B has improved by the invention of the potent nucleos(t)ide analogues entecavir, telbivudine and tenofovir disoproxil. Due to increasing prevalence of lamivudine resistance the appropriate first line therapy may prevent emergence of any new resistance and avoid combination therapy. The present case describes a complex history of chronic hepatitis B in the setting of renal failure after two renal transplants illustrating why lamivudine should not be used as first line treatment option any more. Instead, entecavir offers high antiviral potency, low risk for resistance and possible individual dose titration by an oral solution.