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We retrospectively reviewed 56 fingers with a type 1 flexor digitorum profundus avulsion (jersey finger) injury. Nineteen fingers were treated with a four-strand pull-out suture technique that did not include the distal palmar plate, and 37 were treated with a six-strand pull-out suture technique that included the distal palmar plate. An early active mobilization regimen was used. At follow-up (mean 13 and 14 months, respectively), total active interphalangeal joint motion was significantly better in the six-strand/palmar plate group, as were the results assessed with the Strickland–Glogovac grading system and patient satisfaction according to the Stark criteria. No repair ruptures occurred in this group versus two ruptures in the four-strand/no-palmar-plate group. We consider that the better results can be attributed to a stronger repair, which facilitated early active mobilization. Level of evidence: III

usually when working with data rows in a database, it is necessary to differentiate between the work of different users or to restrict data for other users. However, a problem can arise when multiple users need to access the same data simultaneously. For example, an issue may appear when a user tries to delete a data sample while another user tries to edit it. In this case, data integrity will be violated. To solve this problem, it is necessary to provide a multiuser mode of operation of the client-server application for accessing the database. It can be obtained and organized using the transaction and locking mechanism. However, since there are quite a few different database management systems (DBMS), the proposed approach can differ significantly in the implementation process. Consequently, a different solution is proposed, which is similar to the mechanism of transactions and locks but works differently.

BackgroundThe COVID-19 pandemic has taken a toll on the mental health of the general population. Patients with systemic lupus erythematosus (SLE) were particularly exposed due to many uncertainties linked to the virus and their immunosuppression as well as difficulties to access medical care and their treatment (eg, hydroxychloroquine) during the early pandemic.ObjectivesTo evaluate the difficulties encountered by SLE patients during the early COVID-19 pandemic, and evaluate their impact on patient mental health.MethodsWe conducted a nationwide survey including SLE patients from France metropolitan and overseas territories, recruited by their treating specialist or through a patient association (AFL+). The survey was administered online or in paper form between November 2020 and April 2021, and included questions aiming at evaluating the difficulties encountered during the early COVID-19 pandemic (March to August 2020). The impact on mental health was evaluated using Hospital Anxiety and depression scale (HADS) and post-traumatic stress disorder (PTSD) Checklist for DSM-5 (PCL-5).Results536 SLE patients (91.9% women) of mean age 50 (±14.1) years responded to the survey. The main reported difficulties were issues to access medical care (n = 136, 25.4%) or to obtain hydroxychloroquine treatment (n = 98/389, 25.2%), the loss of employment (n = 85/349, 24.4%) and financial difficulties (n = 75/536, 11%). Hydroxychloroquine shortage was responsible for difficulties in obtaining the drug for 25.2% (98/389) of HCQ-treated patients, and 57 had to interrupt HCQ treatment for a median of 7 days (IQR: 3-17). In the 342 patients with complete assessment, 161 (47.2%) screened positive for anxiety, 141 (41.2%) for depressive syndrome and 128 (38.7%) for PTSD. Multivariate analysis showed that female sex (OR=4.29 [95%CI: 1.39-13.24]), financial issues (OR=2.57 [1.27-5.22]), difficulties to access medical care (OR=2.15 [1.26-3.69]), or to obtain hydroxychloroquine treatment (OR=1.90 [1.06-3.40]) were independently associated with a positive screening for PTSD.ConclusionThe COVID-19 pandemic resulted in a severe burden in SLE patients, including difficulties in access to care and treatment along with high psychological distress. Better understanding these difficulties will allow better prevention and care in times of crisis.Table 1.Factors associated with the development of anxiety, depression or PTSD. Odds ratio (CI95%) using multivariate logistic regression are shown.Patient and pandemic-associated factorsOdds ratio (95%CI) for anxietyOdds ratio (95%CI) for depressionOdds ratio (95%CI) for PTSDFemale sex2.25 (0.97-5.25), p = 0.058ns4.29 (1.39-13.24)p = 0.01Financial difficultiesns2.59 (1.31-5.11)p = 0.0062.57 (1.27-5.22)p = 0.009Difficulties to obtain HCQ1.70 (0.97-2.98)p = 0.065ns1.90 (1.06-3.40)p = 0.03Difficulties to access medical care1.94 (1.15 3.25)p = 0.0122.57 (1.53-4.33)p < 0.00012.15 (1.26-3.69)p = 0.005AcknowledgementsAntonin Folliasson for his help.Disclosure of InterestsMarc SCHERLINGER: None declared, naimah zein: None declared, Jacques-Eric Gottenberg: None declared, Marianne Riviere: None declared, Jean François Kleinmann: None declared, Jean Sibilia: None declared, Laurent Arnaud Speakers bureau: Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, Kezar, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB., Consultant of: consultant for Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, Kezar, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB.

Large enterprises of power engineering (PJSC Power Machines, JSC ROTEK, etc.) often have a large amount of experimental data that is used as a verification basis for the results of numerical simulation. In this case, the task arises of storing the received data and its use for training employees. Small companies do not have full experience and sufficient data to select the optimal settings, which can lead to high accuracy modeling. The solution is to create a database containing recommendations for choosing the settings of the grid and the solver module of modeling software. Recommendations can be generated by verification experiences and simulation results using experimental data.

Three-dimensional (3D) printing or rapid prototyping is a rapidly emerging technology that assists in the generation of 3D objects through the processing of computer images. It has multiple applications in surgery and liver transplantation, in particular, namely medical and patient education, preoperative planning, and bioprinting. 3D printed objects provide a more accurate representation of the organ, while the resemblance of its spatial features assist medical students and surgical residents navigate and understand the underlying anatomy. Living donor liver transplantation is about to enter a new era with better outcomes and fewer complications, while the generation of 3D-bioprinted organs with stem cells embedded in biocompatible scaffolds may become a path to help ameliorate the organ shortage issue. This chapter provides a concise review on the applications of 3D printing on liver transplantation with a particular focus on education, preoperative and intraoperative simulation, and 3D bioprinting.

Summary: Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel. Further, antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue. Collectively, our studies reveal a link between the TMAO-producing enzyme FMO3 and obesity and the beiging of white adipose tissue. : Microbes resident in the human intestine represent a key transmissible environmental factor contributing to obesity and related disorders. Schugar et al. now show that expression of the TMAO-producing enzyme FMO3 is linked to obesity and energy expenditure in both mice and humans. Keywords: microbiota, nutrition, obesity, diabetes, adipose, flavin-containing monooxygenase 3, FMO3

The main objective of the present study was the preparation of the primary reagents of cortisol radioimmunoassay (RIA) using liquid phase double antibody technique. Three basic components were prepared and characterized to obtain valid and accurate system. These components were polyclonal anti-cortisol antibody, 125I-cortisol RIA tracer and cortisol standards. Cortisol requires conjugation step to be real antigen. Therefore, in this study this mandatory conjugation step was performed & characterized. Then formulation, optimization and validation of this liquid phase RIA technique were carried out. This assay is precise, specific and sensitive enough for using as a diagnostic tool for the adrenal cortex status.

Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data

Objective Metabolomic studies suggest plasma levels of bile acids (BAs) are elevated amongst subjects with non-alcoholic fatty liver disease (NAFLD) compared to healthy controls. However, it remains unclear whether or not specific BAs are associated with the clinically relevant transition from nonalcoholic fatty liver (i.e. simple steatosis) to non-alcoholic steatohepatitis (NASH), or enhanced progression of hepatic fibrosis, or genetic determinants of NAFLD/NASH. Methods Among sequential subjects (n=102) undergoing diagnostic liver biopsy, we examined the associations of a broad panel of BAs with distinct histopathological features of NAFLD, the presence of NASH, and their associations with genetic variants linked to NAFLD and NASH. Results Plasma BA alterations were observed through the entire spectrum of NAFLD, with several glycine conjugated forms of the BAs demonstrating significant associations with higher grades of inflammation and fibrosis. Plasma 7-Keto-DCA levels showed the strongest associations with advanced stages of hepatic fibrosis [odds ratio(95% confidence interval)], 4.2(1.2-16.4), NASH 24.5(4.1-473), and ballooning 18.7(4.8-91.9). Plasma 7-Keto-LCA levels were associated with NASH 9.4(1.5-185) and ballooning 5.9(1.4-28.8). Genetic variants at several NAFLD/NASH loci were nominally associated with increased levels of 7-Keto- and glycine-conjugated forms of BAs, and the NAFLD risk allele at the TRIB1 locus showed strong tendency toward increased plasma levels of GCA (p=0.02) and GUDCA (p=0.009). Conclusions Circulating bile acid levels are associated with histopathological and genetic determinants of the transition from simple hepatic steatosis into NASH. Further studies exploring the potential involvement of bile acid metabolism in the development and/or progression of distinct histopathological features of NASH are warranted.

Background Chronic hepatitis B virus (HBV) infection has a mild course in most children that may delay initiation of treatment even when indicated. Unfortunately, a small number of cases can progress rapidly to cirrhosis, which may require liver transplantation (LT) in early adulthood. The aim of this study was to assess the characteristics of HBV-positive young adults who received LT and to evaluate post-transplant outcomes including patient and graft survival and differences between pre- and post-implementation of Model for End-stage Liver Disease (MELD) prioritization. Methods The United Network for Organ Sharing (UNOS) database review was conducted from 1987 to 2012, and a retrospective analysis was performed on all young adult patients (ages 18–35 years) who underwent LT in the United States with a primary diagnosis of HBV or were seropositive for HBV surface antigen at time of LT. Kaplan-Meier analysis was used to assess patient and graft survival in the pre-MELD and post-MELD eras. Factors associated with survival were identified through the use of Cox regression analysis. Results A total of 522 HBV-infected subjects were included. Average age at time of transplant was 28.4 ± 5.2 years; 60.9% were male, 48.6% were white, the mean body mass index was 25 ± 5.5 kg/m2, diabetes was present in 3.9%, hepatocellular carcinoma (HCC) was present in 4.4%, and 10.4% were on dialysis prior to LT. Median follow-up after first LT was 48.2 months [12.5, 109]. During this time, 174 (33.3%) patients died with a mean age at the time of death of 31.6 ± 7.8 years, including 144 of 522 (28%) after the first LT, 26 of 74 (35%) after the second LT, and 4 of 12 (33%) after the third LT. The most common cause of death was graft failure (27.6%), followed by infection (16.6%). Overall, only 58% of patients were alive with their first LT at last follow-up. Kaplan-Meier analysis revealed worse patient and graft survival after re-transplantation in comparison to initial LT. Three hundred thirty subjects were transplanted in the pre-MELD era and 192 were transplanted in post-MELD era. Obesity, HCC, shorter ventilation use, shorter cold ischemia time, and non-white donor race were significantly more common in the post-MELD era (all with P Conclusions LT in young adults for HBV has poor outcomes and can be associated with premature death. These findings should prompt more aggressive evaluation and treatment for HBV in young patients. Superior outcomes in the post-MELD era compared with the pre-MELD era may be attributed to pre-transplant factors, improved surgical technique, and better treatment options for HBV infection.

Patients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for liver transplantation (LT) after successful downstaging. Factors that predict successful downstaging are unclear. We aimed to identify the predictors of successful downstaging of HCC in patients outside MC.We performed a retrospective cohort study on consecutive patients with HCC outside MC who received downstaging with locoregional therapy. Clinical and laboratory variables, tumor characteristics including total tumor volume (TTV) and up-to-7 criteria were recorded. We performed univariate and multivariate logistic regression analyses to identify variables associated with successful downstaging.Of 675 patients with HCC, 90 patients outside MC received downstaging. Fifty-three (59%) patients were successfully downstaged, 37 (41%) failed downstaging. University of California at San Francisco criteria, α-fetoprotein, up-to-7 criteria, TTV, and platelet count were predictors of successful downstaging on univariate analysis. Total tumor volume was an independent predictor of successful downstaging on multivariate logistic regression (P = 0.04, area under receiver operating characteristic curve 0.89 (95% confidence interval, 0.82-0.96). Fifty-two (76%) of 68 patients with TTV less than 200 cm were successfully downstaged, whereas only 1 (4.5%) of 22 patients with TTV greater than 200 cm were successfully downstaged. Forty-five (50%) patients underwent LT. Kaplan-Meier survival rates at 1 and 5 years post-LT were 95.3% and 79.4%, respectively. Patients who were successfully downstaged had better survival than patients who failed downstaging (P0.01).Total tumor volume is a good predictor of successful downstaging of HCC. Patients with TTV less than 200 cm may be considered good candidates for downstaging. Further studies with larger cohort of patients are needed to validate this approach in patients with HCC outside Milan.

Enthusiastic physicians and medical researchers are investigating the role of three-dimensional printing in medicine. The purpose of the current review is to provide a concise summary of the role of three-dimensional printing technology as it relates to the field of pediatric hepatology and liver transplantation.Our group and others have recently demonstrated the feasibility of printing three-dimensional livers with identical anatomical and geometrical landmarks to the native liver to facilitate presurgical planning of complex liver surgeries. Medical educators are exploring the use of three-dimensional printed organs in anatomy classes and surgical residencies. Moreover, mini-livers are being developed by regenerative medicine scientist as a way to test new drugs and, eventually, whole livers will be grown in the laboratory to replace organs with end-stage disease solving the organ shortage problem.From presurgical planning to medical education to ultimately the bioprinting of whole organs for transplantation, three-dimensional printing will change medicine as we know in the next few years.

Nonalcoholic fatty liver disease (NAFLD) is likely to replace Hepatitis C as the leading cause of cirrhosis resulting in liver transplantation (LT) within a few years. Unfortunately, due to the lack of established guidelines for the screening of NAFLD in high-risk populations, many patients present with portal hypertension complications as their first manifestation of NAFLD require a LT evaluation. We aimed to investigate what proportion of patients who underwent LT for NAFLD-cirrhosis had knowledge of their liver disease prior to presenting with portal hypertension complications and to identify differences in clinical parameters between those with and without knowledge of preexisting NAFLD.Consecutive patients who underwent LT for NAFLD-cirrhosis at a tertiary referral center were included in the study. Demographic and clinical data at the time of the first LT evaluation visit were collected, and patient knowledge of previous NAFLD was documented. Ascites, variceal bleeding, hepatic encephalopathy, and thrombocytopenia leading to diagnosis of underlying cirrhosis were considered as the presenting symptoms of portal hypertension. A p 0.05 was considered statistically significant.A total of 124 subjects who received LT for NAFLD-cirrhosis were included, 58 % (n = 72) were male. At the time of the first LT evaluation visit, 60 % had diabetes, the mean body mass index was 33.2 [28.6, 37.6] kg/m(2), and the mean Model for End-Stage Liver Disease (MELD) score was 14.0 [11.0, 19.0]. More importantly, 85/124 patients (68.5 %) had no knowledge of preexisting NAFLD prior to presentation with symptoms of portal hypertension. The presenting symptoms were new-onset ascites in 61 %, hepatic encephalopathy in 25 %, variceal bleeding in 18 %, thrombocytopenia in 9 %, and other in 9 % (non-exclusive). Patients with no prior knowledge of NAFLD were less likely to have a diagnosis of hypercholesterolemia (30 vs. 50 %, p = 0.035) and had a trend toward having higher MELD scores at the time of the first LT evaluation visit (15 vs. 13.5, p = 0.05) and presenting with encephalopathy (25 vs. 10 %, p = 0.06) compared to those with previous knowledge of NAFLD diagnosis.The majority of patients undergoing liver transplant evaluation for NAFLD-cirrhosis are not aware of underlying NAFLD until they present with features of portal hypertension. New guidelines should consider screening for NAFLD in certain high-risk groups as more effective treatments for NAFLD are emerging.

Background Higher rates of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection have been reported. This can influence their selection for LT and post-LT monitoring. Objective The aim of this work was to compare the rates of post-LT HCC recurrence and survival in HBV and non-HBV patients with the use of the United Network for Organ Sharing (UNOS) database. Methods After accessing the UNOS database, we analyzed patients with HCC stage T2 who underwent LT from cadaveric donors on or after August 24, 1998. Propensity score matching based on age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to match HBV-HCC patients to HCC patients with other underlying liver diseases: hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable analysis (with the use of propensity score, age, sex, and race) were used to assess post-LT HCC recurrence and overall survival. Results A total of 4,480 HCC patients were matched. Their average age was 57 ± 7.8 years and average calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of tumor recurrence compared with ALD and NASH patients, respectively, and a 32% lower hazard of death than patients with HCV + ALD. There was no evidence of any other significant difference in HCC recurrence or survival among the etiology groups. Conclusions HCC recurrence and survival rates following LT for HCC patients with chronic HBV infection are similar to those of HCC patients with other underlying liver diseases. These findings support LT as a viable option for HCC-HBV patients.

Alcoholic hepatitis, in its severe form, is a devastating acute condition that requires early recognition and specialized tertiary medical care. This paper summarizes its epidemiology, pathophysiology, assessment, and treatment.

With the increasing age of recipients undergoing orthotopic liver transplant (OLT), there is need for better risk stratification among them. Our study aims to identify predictors of poor outcome among OLT recipients ≥ 60 yr of age. All patients who underwent OLT at Cleveland Clinic from January 2004 to April 2010 were included. Baseline patient characteristics and post-OLT outcomes (mortality, graft failure, length of stay, and major post-OLT cardiovascular events) were obtained from prospectively collected institutional registry. Among patients ≥ 60 yr of age, multivariate regression modeling was performed to identify independent predictors of poor outcome. Of the 738 patients included, 223 (30.2%) were ≥ 60 yr. Hepatic encephalopathy, platelet counts45,000/μL, total serum bilirubin3.5 mg/dL, and serum albumin2.65 mg/dL independently predicted poor short-term outcomes. The presence of pre-OLT coronary artery disease and arrhythmia were independent predictors of poor long-term outcomes. Cardiac causes represented the second most common cause of mortality among the elderly cohort. Despite that, this carefully selected cohort of older OLT recipients had outcomes that were comparable with the younger recipients. Thus, our results show the need for better pre-OLT evaluation and optimization, and for closer post-OLT surveillance, of cardiovascular disease among the elderly.

After liver transplant (LT), the risk of hepatocellular carcinoma (HCC) recurrence is partially dependent on the degree of immunosuppression. We aimed to determine whether assessing net state of CD4(+) T-cell function after LT could determine those at risk for HCC recurrence.One hundred thirty-seven patients with cirrhosis who underwent LT for HCC were followed for recurrence of HCC. All patients had serial CD4(+) assay performed prospectively. Cox regression analysis was used to assess factors associated with HCC recurrence. Kaplan-Meier plots were used to assess the association between CD4(+) ATP values and hazard of HCC recurrence.The mean follow-up time was 3.1 ± 1.5 years, during which 14 patients (10%) had HCC recurrence. Patients with combined post-LT CD4(+) T-cell function area under curve (AUC)675 had 6.9 (95% CI 2.0-22.0) times greater hazard of HCC recurrence than those with CD4(+) T-cell function AUC ≥675 (P.001). Less immunosuppression (ATP AUC ≥675) in those beyond Milan conferred a similar risk of recurrence as patients transplanted within Milan (P = .064).Lower cumulative CD4(+) T-cell function post-LT predicted a higher risk of HCC recurrence. These findings may have implications toward management of HCC patients after LT.

Introduction De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. Methods Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies. Results A total of 30 patients with plasma cell hepatitis were identified. Underling liver disease were hepatitis C virus (n = 11) and non–hepatitis C virus-related disease (n = 19). The interval period from liver transplantation to development of plasma cell hepatitis was 20 (2–246) months during 6 (1.5–25.8) years after liver transplantation. The mean international autoimmune hepatitis score and frequency of acute cellular rejection episode prior to the diagnosis of plasma cell hepatitis were lower in the patients with hepatitis C virus than those underlying non–hepatitis C virus-related disease. Twenty-seven patients (90.0%) showed complete biochemical response to plasma cell hepatitis treatment, but 10 (37.0%) patients relapsed. During the median 72 months' follow-up after liver transplantation, 9 (30.0%) patients progressed to cirrhosis (median 37 months) and 10 (33.3%) patients died or were retransplanted. Conclusions This long-term clinical observation shows that de novo autoimmune hepatitis represents one cause of graft loss in patients with or without hepatitis C virus. Although most patients exhibit a good response to medical therapy, de novo autoimmune hepatitis is likely to recur and progress to liver cirrhosis.

Thrombocytopenia is a well-known complication of liver cirrhosis. Although the pathogenesis of thrombocytopenia is not well understood, splenic congestion resulting from portal hypertension is considered the most significant underlying mechanism. Therapeutic measures that lower portal hypertension, such as transjugular intrahepatic portosystemic shunt (TIPS), are expected to improve thrombocytopenia associated with liver cirrhosis. At present, there are few studies on the effect of TIPS on platelet counts, and the results are conflicting. This article assesses the effect of TIPS on thrombocytopenia associated with liver cirrhosis. Methods: Seventy-four patients with liver cirrhosis who were referred for TIPS were included in this study. Platelet counts were measured on 3 different occasions over a 3-month period prior to and following placement of TIPS. Thrombocytopenia was defined as a platelet count of 150,000/mm3 or less. Moderate thrombocytopenia was defined as a platelet count of 100,000/mm3 or less. Severe thrombocytopenia was defined as a platelet count of 50,000/mm3 or less. A significant increase in platelet count was defined as a 20% or higher increase from pre-TIPS values. The portosystemic pressure gradient (PSPG) was measured before and after placement of TIPS. The patency of the shunt was checked using Doppler ultrasound 24 hours and 3 months after the procedure. Results: Thirty-four of the 74 patients (46%) who underwent TIPS showed a significant increase in platelet count, with an average increase of 22% (P

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. Liver Transpl 20:544–551, 2014. © 2014 AASLD.

Background and aims. Most portal vein thromboses (PVT) in cirrhotics are discovered incidentally. While case series demonstrate improved portal vein patency with anti-coagulation, there is little information on impact of PVT on morbidity and mortality. This study aimed to compare morbidity and mortality in cirrhotics with untreated PVT with those without PVT. Material and methods. Cirrhotics evaluated for orthotopic liver transplant in a single large transplant center were prospectively followed. Subjects had contrast CT or MRI at initial evaluation and serial imaging every 6 months until transplantation, removal from the list or death. Univariate and multivariate Cox regression analysis were used to assess associations between new PVT and factors of interest. Results. Of the 290 prospectively followed cirrhotics who met inclusion criteria, PVT was detected in 70 (24.1%)-47 had PVT at the time of initial evaluation and 23 developed one during the pre-transplant study period. A third of the patients with PVT had re-canalization or spontaneous resolution of thrombus while awaiting transplantation. There was no difference in the pre or posttransplant mortality between cirrhotics with and without PVT. Conclusion. Cirrhotics with untreated PVT fared equally well as those without PVT before and after transplantation. Further studies with larger numbers of patients are needed to determine if anticoagulation therapy truly improves outcomes in cirrhotics with portal vein thrombosis.

The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers.

Spontaneous bacterial peritonitis (SBP) is common in cirrhotic patients and has high associated mortality. SBP is preventable with antibiotic prophylaxis. The aim of this study was to identify patients at high risk to develop SBP based on their peripheral blood CD4 T-cell function.Fifty-seven patients with cirrhosis and ascites were followed for the development of SBP. All patients had CD4 assay performed through phytohemagglutinin stimulation of peripheral blood, which was quantified by measuring adenosine triphosphate (ATP) release by luciferin/luciferase assay. A receiver operating characteristic curve was used to evaluate the CD4 assay as a predictor of SBP. A time to SBP or death analysis was performed and Kaplan-Meier plots were used to assess the association between CD4 ATP concentration and hazard of SBP or mortality.The median follow-up time was 7.3 (4.8, 13) months. Patients who developed a first episode of SBP had a lower median CD4 ATP concentration compared to patients without SBP (120 vs. 239 ng/mL; P0.001). The best independent predictor of SBP was peripheral CD4 function and an ATP level of ≤201 ng/mL provides 83% sensitivity and 71% specificity for future prediction of SBP. Patients with ATP concentration ≤201 ng/mL had a 4.7 times greater hazard of developing SBP than those with ATP level201 ng/mL (P0.001). Patients with SBP had 7.9 times higher hazard of mortality then those without SBP (P=0.008).The risk of developing SBP was significantly increased in patients with cirrhosis and ascites who had depressed CD4 T-cell function.

Chronic liver disease (CLD) starts or becomes established in the adolescent and young adult (AYA) age group. This study aimed to estimate trends in CLD prevalence among US AYAs and to assess factors associated with CLD. Cross-sectional data from 14,547 AYAs (population-weighted N = 68,274,386) aged 15–39 years enrolled in the National Health and Nutrition Examination Survey from 1988 to 2012 were used. Nonalcoholic fatty liver disease (NAFLD) was defined as elevated alanine aminotransferase (>19 U/L for females and >30 U/L for males) in subjects with BMI ≥ 25 kg/m2; alcoholic liver disease (ALD) as excessive alcohol use (≥3 drinks/day for men and ≥2 drinks/day for women) and elevated aminotransferases after excluding alternative etiologies. Participants were considered hepatitis C virus (HCV) positive if antibody to HCV and HCV-RNA was positive. There was a sharp increase in the prevalence of CLD from 12.9% in 1988–1994 to 28.5% in 1999–2004 that remained stable after that (27.7%). NAFLD was the most common etiology accounting for 22% of all CLD in the later period. The prevalence of ALD has been steadily increasing throughout the years, while HCV has been decreasing. On multivariate analysis, being overweight/obese, Mexican–American ethnicity, later study period, older age, and male gender, were associated with higher odds of having CLD. More than one quarter of US AYAs might be affected by CLD. CLD prevalence in this age group has more than doubled over the past three decades mainly due to rise in NAFLD prevalence.

On an otherwise pleasant evening during the first week of July 2016, a businessman who was a citizen of the United Arab Emirates visiting Cleveland for medical treatment was falsely accused of links to a terror organization. Officers stormed his hotel with assault rifles and handcuffed and arrested

To the Editor,We read with interest the article by Than et al. [1] published in Scandinavian Journal of Gastroenterology. An analysis of 17 autoimmune hepatitis (AIH) patients from two tertiary liv...

Background Current recommended regimens to treat patients with hepatitis C virus (HCV) infection after liver transplantation include the use of ribavirin (RBV). Limited data are available on the efficacy of RBV-free regimens posttransplant, particularly the use of sofosbuvir (SOF)/ledipasvir (LDV) without RBV in this patient population. We aimed to assess the efficacy and safety of SOF/LDV fixed-dose combination without RBV in patients with HCV recurrence posttransplant. Methods This is a retrospective study of 46 patients with HCV recurrence posttransplant. SOF/LDV without RBV was used for 12 weeks in patients with early-stage fibrosis (F0-F2) or for 24 weeks in those with advanced fibrosis (F3-F4) and/or cholestatic hepatitis. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment. Secondary outcomes included relapse after treatment and adverse events. Results Forty-six patients, with a mean age of 62 ± 8 years, a median duration since time of transplant of 904 days (range, 78-3525 days), an HCV genotype 1, and a mean baseline viral load of 7.79 million IU/mL, were treated. Of these, 32 patients were treated for 12 weeks, and 14 patients were treated for 24 weeks. Twenty-five patients (54%) were treatment experienced (21 with interferon and 4 with SOF). All 46 patients (100%) achieved sustained virological response (SVR) 12. Neither virologic relapses nor serious adverse events were noted. Conclusions The combination of SOF/LDV without RBV for 12 or 24 weeks produced 100% SVR 12 in patients with HCV recurrence after liver transplantation. The use of RBV may not be necessary to achieve SVR in this patient population.

Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the "gold standard" of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.

Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of obesity and insulin resistance. The aim of this study was to determine the frequency of NASH as an indication for liver transplantation (LT) in children and young adults and to characterize patient and graft survival. The study included all children and young adult patients (up to the age of 40 years) who underwent LT in the United States for NASH cirrhosis from the 1987 to 2012 United Network for Organ Sharing (UNOS) database. Kaplan-Meier analysis was used to assess patient and graft survival. A total of 330 patients were included, 68% were Caucasian, and the mean BMI was 33.6 ± 6.3. Age at time of LT ranged between 4 and 40 years (mean 33.9 ± 6.6 years). Fourteen subjects were

As survival after orthotopic liver transplantation (OLT) improves, cardiovascular (CV) disease has emerged as the leading cause of non-graft-related deaths. The aims of our study were to determine the cumulative risk of CV events after OLT and to analyze predictive risk factors for those experiencing a CV event after OLT. We identified all adult patients who underwent OLT at our institution for end-stage liver disease between October 1996 and July 2008. The cumulative risk of CV events after OLT was analyzed with the Kaplan-Meier method. Multivariate logistic regression analysis was used to identify factors independently associated with CV events after OLT. In all, 775 patients were included in our study cohort (mean age of 53.3 years, female proportion = 44%, Caucasian proportion = 84%, median follow-up = 40 months). The most common indications for OLT were hepatitis C virus (33.2%), alcohol (14.5%), and cryptogenic cirrhosis (12.7%). Eighty-three patients suffered 1 or more CV events after OLT. Posttransplant metabolic syndrome was more prevalent in patients with CV events versus patients with no CV events (61.4% versus 34.1%, P < 0.001). According to a multivariate analysis, independent predictors of CV events were an older age at transplantation [odds ratio (OR) = 1.2, addition of 95% confidence interval (CI) = 1.1-1.3, P = 0.006], male sex (OR = 2.0, 95% CI = 1.2-3.3, P = 0.01), posttransplant diabetes (OR = 2.0, 95% CI = 1.3-3.3, P = 0.003), posttransplant hypertension (OR = 1.8, 95% CI = 1.1-3.0, P = 0.02), and mycophenolate mofetil (OR = 2.0, 95% CI = 1.3-3.2, P = 0.003). Among post-OLT patients, the cumulative risk at 5 years of 13.5%, respectively. In conclusion, cardiac complications after liver transplantation are common (Approximately 10% of patients experience 1 or move cv events). Patients with posttransplant hypertension and diabetes, which are modifiable risk factors, are approximately twice as likely to experience a CV event.

Background. A pretransplant positive crossmatch in combined liver kidney transplants (CLK) is not considered a contraindication based on the reported immunoprotection conferred by the liver allograft. However, antibody-mediated rejection of the kidney in CLK has been reported recently. This prompted our study to investigate the impact of presensitization on CLK recipient outcomes. Methods. We examined kidney allograft and patient survival by indication of sensitization using Scientific Registry of Transplant Recipients data on CLK performed from 1995 to 2008. We defined sensitization as panel reactive antibody (PRA) more than 10% or a positive T-cell crossmatch (TXM). Results. Among 2484 CLK recipients with available PRA or TXM information, 30% had positive TXM or PRA more than 10%. Among those with TXM information, 12% had a positive crossmatch (n=234). In univariate analyses, patient (P=0.002) and overall kidney graft survival (P=0.015) were significantly diminished among sensitized patients. Differences in patient survival translated to estimated half-lives of 10.3 years among nonsensitized recipients versus 7.8 years among sensitized recipients, In multivariable Cox models, allosensitization was independently associated with patient death (adjusted hazard ratio=1.22, 95% CI, 1.04–1.43) and overall kidney graft loss (adjusted hazard ratio=1.16, 95% CI, 1.00–1.36). Conclusions. These results suggest a negative impact of presensitization on patient and overall renal allograft survival in CLK. Accordingly, presensitization may need to be considered in risk stratification and clinical management of CLK.

The extrinsic death receptor-mediated pathway of apoptosis is involved in nonalcoholic steatohepatitis (NASH) development. Our aims were to create and validate a noninvasive prediction model for NASH diagnosis based on specific circulating markers of apoptosis.Our initial cohort consisted of 95 consecutive patients undergoing a liver biopsy for clinically suspected NASH. Blood was obtained from each patient at the time of liver biopsy. Plasma caspase 3 generated cytokeratin-18 fragments (CK-18), soluble Fas (sFas), and soluble Fas ligand (sFasL) were measured. Histology was assessed by an experienced hepatopathologist. The validation cohort consisted of 82 consecutive patients that underwent liver biopsy at the time of bariatric surgery.Patients with NASH had significantly higher levels of CK-18 and sFas than patients in the "not NASH" group [median (25th, 75th percentile): 508 (280, 846) U/L versus 176 (131, 224) U/L (p0.001), and 11.8 (7.8, 12.5) ng/ml versus 5.9 (4.8, 8.3) ng/ml (p0.001), respectively]. A significant positive correlation was revealed between the apoptosis markers and liver histopathology independent of other metabolic factors. A prediction model was generated including CK-18 fragments and sFas levels that showed an AUC of 0.93 and 0.79 in the initial and validation cohorts, respectively. A cutoff value using this model predicted NASH with a sensitivity and specificity of 88% and 89%, respectively.Quantification of circulating levels of two apoptotic markers accurately predicts the presence of NASH, supporting the potential usefulness of these markers in clinical practice for noninvasive diagnosis of NASH.