Lower tacrolimus trough levels in the late period after living donor liver transplantation contribute to improvements in long-term clinical outcomes

Background: Previous studies have emphasized the need to reduce tacrolimus(TAC) trough levels in the early post-liver transplantation(LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear.Methods: We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: 3 ng/m L group, 3–5 ng/m L group, and5 ng/m L group. The complications and adverse effects of TAC were analyzed.Results: Each group showed similar rejection, graft loss and mortality. Patients achieved the 5 ng/m L state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups.Conclusions: Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.     

Prognostic value of decision criteria for emergency liver transplantation in patients with wild mushroom induced acute liver injury

Background: The reported mortality rate of mushroom-induced acute liver failure with conventional treatment is 1.4%–16.9%. Emergency liver transplantation may be indicated and can be the only curative treatment option. This study aimed to assess the prognostic value of criteria for emergency liver transplantation in predicting 28-day mortality in patients with mushroom-induced acute liver injury.Methods: A retrospective cohort study was performed between January 2005 and December 2015. All adult patients aged≥18 years admitted with mushroom intoxication at our emergency department were evaluated. All patients with acute liver injury, defined as elevation of serum liver enzymes(5 times the upper limit of normal, ULN) or moderate coagulopathy(INR 2.0) were included. The ability of the King's College, Ganzert's, and Escudié's criteria to predict 28-day mortality was evaluated.Results: Of the 23 patients with acute liver injury following mushroom intoxication, 10(43.5%) developed acute liver failure and subsequently died. The mean time interval from ingestion to death was 11.3 ± 6.6 days. Eight patients fulfilled Ganzert's criteria, while 10 patients fulfilled the King's College and Escudié's criteria for emergency liver transplantation. King's College and Escudié's criteria had 100% accuracy in predicting 28-day mortality; however, Escudié's criteria were able to identify fatal cases earlier.Conclusions: Escudié's criteria demonstrated the best performance with 100% accuracy and the ability to promptly identify fatal cases of mushroom-induced acute liver failure.     

A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation

Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.     

The changes of intraoperative body temperature in adult liver transplantation: A retrospective study

Background: Body temperature is poorly regulated in patients with end-stage liver disease. Due to the prolonged surgery time and anhepatic time as well as the complex surgical procedures performed in liver transplantation, the body temperature fluctuates greatly. This study investigated the effect of intraoperative body temperature fluctuations on the prognosis of liver recipients. Methods: The body temperatures of liver recipients recorded from the induction of anesthesia(T 0) until the end of surgery(T 14) were retrieved. The patients were divided into two groups: the hypothermia group( 35 °C and ≥ 5 min) and the normothermia group( ≥ 35 °C or 35 °C but 5 min). Intraoperative and postoperative variables were compared between the two groups, and the correlations between the duration of hypothermia and the medical variables were analyzed. Results: Of the 107 patients, 67 patients were in the normothermia group, and 40 in the hypothermia group. The lowest body temperature was at 5 min after reperfusion for the whole cohort. Compared with the normothermia group, patients in the hypothermia group were more prone to bleeding, had a longer intubation time and increased rates of bacterial infection and acute pulmonary edema after liver transplantation( P 0.05). Hypothermia time was positively correlated with bleeding volume, intubation time, units of blood transfusions and intensive care stay, but negatively correlated with urine output. Conclusions: The intraoperative body temperature exhibited a graphical "V" trend, and the lowest temperature was at 5 min after reperfusion. The longer the duration of hypothermia, the more unfavourable the prognosis.     

Optimized postconditioning algorithm protects liver graft after liver transplantation in rats

Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.     

Potential application of ultrasound-guided thermal ablation in rare liver tumors

Background

With the advances of imaging techniques, the detection rate of rare liver tumor is increased. However, the therapeutic strategies of the rare liver tumors remain limited.

New-onset hyperglycemia immediately after liver transplantation: A national survey from China Liver Transplant Registry

Background: New-onset hyperglycemia(NOH) is a common phenomenon after liver transplantation(LT),but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after LT.Methods: The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic agent.Results: Of 3339 liver recipients, 1416(42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis,and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients(P 0.05). The independent risk factors of NOH were donor warm ischemic time 10 min, cold ischemic time 10 h, anhepatic time 60 min, recipient model for end-stage liver disease score 30, moderate ascites and corticosteroid usage(P 0.05). Liver enzymes(alanine aminotransferase and gammaglutamyltranspeptidase) on post-transplant day 7 significantly correlated with NOH(P 0.001).Conclusions: NOH leads to increased morbidity and mortality in liver recipients. Close surveillance and tight control of blood glucose are desiderated immediately following LT particularly in those with delayed graft function and receiving corticosteroid. Strategic targeting graft ischemic injury may help maintain glucose homeostasis.     

Glissonian approach combined with major hepatic vein first for laparoscopic anatomic hepatectomy

Background

Laparoscopic anatomic hepatectomy remains challenging because of the complex interior structures of the liver. Our novel strategy includes the Glissonian approach and the major hepatic vein first, which serves to define the external and internal landmarks for laparoscopic anatomic hepatectomy.

Comparative symptom biochemistry between moderate and advanced heart failure

Background

We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF).

Age and pain as predictors of discomfort in patients undergoing transfemoral percutaneous coronary interventions

Background

Transfemoral percutaneous coronary intervention (PCI) requires strict bed rest, causing pain and discomfort in patients. However, no studies have investigated this issue.

Cognitive impairment predicts mortality in outpatient veterans with heart failure

Background

In our prior study of 250 outpatient veterans with heart failure (HF), 58% had unrecognized cognitive impairment (CI) which was linked to worsened medication adherence. Literature suggests HF patients with CI have poorer clinical outcomes including higher mortality.

Chimeric antigen receptor-engineered T-cell therapy for liver cancer

Background

Chimeric antigen receptor-engineered T-cell (CAR-T) therapy is a newly developed immunotherapy used in the treatment of cancers. Because CAR-T therapy has shown great success in treating CD19-positive hematological malignancies, its application has been explored in the treatment of solid tumors, such as liver cancer. In this review, we discuss the immune characteristics of liver cancer, the obstacles encountered during the application of CAR-T therapy, and preclinical and clinical progress in the use of CAR-T therapy in patients with liver cancer.

Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease: Either non-obese or obese Chinese population

Background: Non-alcoholic fatty liver disease(NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese population.Methods: Data collected from subjects registered at Taichung Veterans General Hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver(normal or NAFLD), and body mass index(BMI) levels(non-obese if BMI 25 kg/m~2 or obese if BMI ≥ 25 kg/m~2).Results: There were 745, 208, 770 and 285 patients enrolled in four groups labeled non-obese normal liver(group A), non-obese NAFLD(group B), obese normal liver(group C) and obese NAFLD(group D),respectively. The highest ratio of metabolic syndrome existed in the group B(26.9%), followed by group A(11.7%), group D(10.9%) and finally the group C(5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02) and glucose(OR = 1.02; 95% CI:1.01–1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02). The positive association was most significant in all cases(adjusted OR = 2.41; 95% CI: 1.78–3.24), especially in non-obese individuals(OR = 2.81; 95% CI: 1.92–4.12).Conclusions: Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.     

Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

Background: Hepatitis B virus(HBV)-associated acute-on-chronic liver failure(HBV-ACLF) is a lifethreatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum mi RNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF.Methods: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to30 chronic asymptomatic HBV carriers as controls. The mi RNAs expressions were measured by real-time quantitative PCR(q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed mi RNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model.Results: Real-time q-PCR indicated that serum miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and mi R-122-3 p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+-1.72 × INR-4.963 × gastrointestinal bleeding(Yes = 0; No = 1)-0.278 ×(mi R-122-3 p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve(AUROC) was 0.847.Conclusions: Expression levels of these mi RNAs(miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.     

Ideal Cardiovascular Health Is Inversely Associated with Nonalcoholic Fatty Liver Disease: A Prospective Analysis

Background

Cardiovascular health has been proven to be associated with major cardiometabolic diseases. However, little is known of associations between cardiovascular health and nonalcoholic fatty liver disease.

Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction

Background

Endoscopic biliary decompression using bilateral self-expandable metallic stent (SEMS) placed using the stent-in-stent (SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction (MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO.

A Qualitative,Cross-Sectional Study of Positive and Negative Comments of Residency Programs Across 9 Medical and Surgical Specialties

IMPORTANCE

Residency applicants often use social media to discuss the positive and negative features of prospective training programs. An examination of the content discussed by applicants could provide guidance for how a medical education faculty can better engage with prospective trainees and adapt to meet the educational expectations of a new generation of digital-native physicians.

Restoration of common bile duct diameter within 2 weeks after endoscopic stone retraction is a preventive factor for stone recurrence

Background: Little information is available about the relationship between restoration of common bile duct(CBD) diameter after endoscopic stone retraction and recurrence of CBD stones in elderly patients.The present study was to determine whether restoration of CBD diameter is a preventive factor for CBD stone recurrence in elderly patients who underwent endoscopic retrograde cholangiopancreatography(ERCP).Methods: From January 2006 to December 2010, 238 patients underwent the first and the second session of ERCP for the removal of CBD stones. Among them, 173 were over 65 years old. These patients were divided into recurrent group and non-recurrent group. Restoration of CBD diameter and patients' characteristics were compared.Results: There was no statistical difference in patients' characteristics, associated diseases, or ERCP-related complications between the two groups. Reduction of CBD diameter was significantly larger in the nonrecurrent group(2.7 ± 1.7 mm) compared to that in the recurrent group(1.4 ± 2.3 mm, P = 0.002). The proportion of patients with restoration of CBD diameter were significantly lower in the recurrent group(6/42, 14.3%) compared with that in the non-recurrent group(67/131, 51.1%)(P 0.01).Conclusions: There is an inverse relationship between restoration of CBD diameter and CBD stone recurrence. Therefore, patients without restoration of CBD diameter within 2 weeks after endoscopic stone removal should be monitored more frequently.     

Glycogenic hepatopathy

Background

Glycogenic hepatopathy (GH) is a disorder associated with uncontrolled diabetes mellitus, most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes. GH may be diagnosed also after elevated liver enzymes in routine blood tests. GH usually regresses after tight glycemic control. Progression to end-stage liver disease has never been reported. This review aims to increase the awareness to this disease, to suggest a pathway for investigation that may reduce the use of unnecessary tests, especially invasive ones.

Use of Statins for Primary Prevention: Selection of Risk Threshold and Implications Across Race and Gender

Background

The 2016 U.S. Preventive Services Task Force (USPSTF) guidelines for primary prevention statin therapy are more restrictive than the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. There are important differences in how application of the risk thresholds from these guidelines would impact particular segments of the U.S. population.