Acute graft-versus-host disease after liver transplantation in a close contact with COVID-19: A case report.

Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to "isolation ward" due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.

Challenging management of severe chronic disorders in acute pandemic situation: Chronic liver disease under COVID-19 pandemic as the proof-of-principle model to orchestrate the measures in 3PM context.

Chronic liver disease management is a comprehensive approach requiring multi-professional expertise and well-orchestrated healthcare measures thoroughly organized by responsible medical units. Contextually, the corresponding multi-faceted chain of healthcare events is likely to be severely disturbed or even temporarily broken under the force majeure conditions such as global pandemics. Consequently, the chronic liver disease is highly representative for the management of any severe chronic disorder under lasting pandemics with unprecedented numbers of acutely diseased persons who, together with the chronically sick patient cohorts, have to be treated using the given capacity of healthcare systems with their limited resources. Current study aimed at exploring potentially negative impacts of the SARS CoV-2 outbreak on the quality of the advanced chronic liver disease (ACLD) management considering two well-classified parameters, namely, (1) the continuity of the patient registrations and (2) the level of mortality rates, comparing pre-COVID-19 statistics with these under the current pandemic in Slovak Republic. Altogether 1091 registrations to cirrhosis registry (with 60.8% versus 39.2% males to females ratio) were included with a median age of 57 years for patients under consideration. Already within the very first 3 months of the pandemic outbreak in Slovakia (lockdown declared from March 16, 2020, until May 20, 2020), the continuity of the patient registrations has been broken followed by significantly increased ACLD-related death rates. During this period of time, the total number of new registrations decreased by about 60% (15 registrations in 2020 versus 38 in 2018 and 38 in 2019). Corresponding mortality increased by about 52% (23 deaths in 2020 versus 10 in 2018 and 12 in 2019). Based on these results and in line with the framework of 3PM guidelines, the pandemic priority pathways (PPP) are strongly recommended for maintaining tertiary care uninterrupted. For the evidence-based implementation of PPP, creation of predictive algorithms and individualized care strategy tailored to the patient is essential. Resulting classification of measures is summarized as follows:The Green PPP Line is reserved for prioritized (urgent and comprehensive) treatment of patients at highest risk to die from ACLD (tertiary care) as compared to the risk from possible COVID-19 infection.The Orange PPP Line considers patients at middle risk of adverse outcomes from ACLD with re-addressing them to the secondary care. As further deterioration of ACLD is still probable, pro-active management is ascertained with tertiary center serving as the 24/7 telemedicine consultation hub for a secondary facility (on a physician-physician level).The Red PPP Line is related to the patients at low risk to die from ACLD, re-addressing them to the primary care. Since patients with stable chronic liver diseases without advanced fibrosis are at trivial inherent risk, they should be kept out of the healthcare setting as far as possible by the telemedical (patient-nurse or patient- physician) measurements. The assigned priority has to be monitored and re-evaluated individually-in intervals based on the baseline prognostic score such as MELD. The approach is conform with principles of predictive, preventive and personalized medicine (PPPM / 3PM) and demonstrates a potential of great clinical utility for an optimal management of any severe chronic disorder (cardiovascular, neurological and cancer) under lasting pandemics.

The influence of recipient SLCO1B1 rs2291075 polymorphism on tacrolimus dose-corrected trough concentration in the early period after liver transplantation.

PURPOSE: To explore the relationship between rs2291075 polymorphism in SLCO1B1 gene, which encodes an influx transmembrane protein transporter, and tacrolimus dose-corrected trough concentration (C/D, ng ml-1 mg-1 kg-1) in the early period after liver transplantation. METHODS: CYP3A5 rs776746 and SLCO1B1 rs2291075 polymorphisms of 210 liver transplantation patients and their corresponding donor livers were assessed by PCR amplification and DNA sequencing. The influence of gene polymorphisms on C/D values of tacrolimus was analyzed. The early postoperative period after liver transplantation was divided into the convalescence phase (1-14 days) and stationary phase (15-28 days) according to the change of liver function and tacrolimus C/D values. RESULTS: The combined analysis of donor and recipient CYP3A5 rs776746 could distinguish the metabolic phenotype of tacrolimus into three groups: fast elimination (FE), intermediate elimination (IE), and slow elimination (SE), which was entitled the FIS classification system. Tacrolimus C/D ratios of recipient SLCO1B1 rs2291075 CT and TT carriers were very close and were significantly lower than those of recipient SLCO1B1 rs2291075 CC genotype carriers in convalescence phase (p = 0.0195) and in stationary phase (p = 0.0152). There were no statistically significant differences between tacrolimus C/D ratios of patients carried with SLCO1B1 rs2291075 CT, TT genotype donors, and those carried with SLCO1B1 rs2291075 CC genotype donors. A model consisting of tacrolimus daily dose, total bilirubin, FIS classification, and recipient SLCO1B1 rs2291075 could predict tacrolimus C/D ratios in the convalescence phase by multivariate analysis. However, recipient SLCO1B1 rs2291075 genotype failed to enter forecast model for C/D ratios in stationary phase. Recipient SLCO1B1 rs2291075 genotype had significant effect on tacrolimus C/D ratios in convalescence phase (p = 0.0300) and stationary phase (p = 0.0400) in subgroup, which excluded the interference come from donor and recipient CYP3A5 rs776746. CONCLUSION: SLCO1B1 rs2291075 could be a novel genetic locus associated with tacrolimus metabolism. The combined analysis of donor and recipient CYP3A5 rs776746, recipient SLCO1B1 rs2291075 genotypes, could be helpful to guide the personalized administration of tacrolimus in early period after liver transplantation.

Effect of recipient SLCO1B1 rs2291075 polymorphism on tacrolimus dose-corrected trough concentration in early postoperative period of liver transplantation / 中国临床药理学与治疗学

AIM: To explore the relationship between SLCO1B1 rs2291075 polymorphism and tacrolimus (FK506) dose-corrected trough concentration (C/D, ng•mL

Clinical application of piggyback liver transplantation and modified surgery / 中华消化外科杂志

Orthotopic liver transplantation (OLT) was first implemented by Starzl in 1963.With the development of liver transplantation,Tzaris was the first to report piggyback liver transplantation (PBLT) in 1989.The fundamental difference between OLT and PBLT:end to end vascular anastomosis between the donor and recipient is performed after diseased liver resection with the posthepatic inferior vena cava in OLT,while PBLT is to preserve the recipient's hepatic vein and end to end vascular anastomosis between interior vena cava of donor and shaped hepatic vein is performed.However in the clinical practice,the above two techniques cannot meet the needs of clinical liver transplantation technology.Since 1993 the author has implemented a series of improvements in liver transplantation technology based on PBLT and performed ameliorated piggyback liver transplantation (APBLT).This article focuses on the technical characteristics and clinical application of APBLT.

Research progress on machine perfusion to reduce the incidence of non-anastomotic biliary stricture after liver trans-plantation / 中华肝胆外科杂志

Liver transplantation has become the most effective treatment for end-stage liver diseases.Due to the shortage of organ,more and more extended criteria donors (ECD) grafts had been used,which expand the liver pool.However,a series of complications post transplantation were caused by ischemia,hypoxia,steatosis and so on.The non-anastomotic biliary strictures after liver transplantation is one of the major complications when the ECD donors was be used in clinic.The study on the protective effect of machine perfusion on liver donors is too numerous to list,and existing studies have found that MP can reduce the incidence of NAS after liver transplantation.This review provides an overview of the pathogenesis of NAS and the reduction incidence of NAS by MP.

Acute renal failure in acute liver failure patients undergoing liver transplantation / 中华普通外科杂志

Objective To investigate the causes of acute renal failure(ARF)after orthtopic liver transplantation(OLT)in patients of acute liver failure(ALF)and the effects of systemic therapy based on continuous renal replacement(CRRT).Methods Clinical data of 412 patients who underwent liver transplantations between January 2001 and June 2006 were analyzed retrospectively (all the cases were followed up to June 2007).According to UNOS grading scale,54 patients were of acute liver failure(UNOS 1 and 2A).Posttransplant ARF developing in 17 cases underwent a systemic therapy based on CRRT as well as anti-rejection,anti-infection and nutrition support.The perioperative courses,complications,causes of death and follow up results were analyzed.Results There were no severe complications during CRRT.Perioperative mortality was 5.4%and 58.8%in patients without ARF and those with ARF respectively.the rate of complications was 35.1%vs 100%.1 year survival rate Was 89.2% vs 41.2%.3 year survival rate was 81.1% vs 41.2%.Condusions The effect of surgery mainly depends on the function of liver and other vital organs.The ALF recipients suffered from a high perioperative mortality,especially those with posttransplant ARL.The systemic therapy based on CRRT benefits patients with postoperative ARF.

Relationship between clinicopathologic features and neoplasm recurrence,prognosis in hepatocellular carcinoma after liver transplantation / 中华器官移植杂志

Objective To study the risk factors affecting neoplasm recurrence and survival of hepatocellular carcinoma(HCC)following liver transplantation(LT).Methods The clinicopatholo gic data,neoplasm recurrence and survival results of 118 patients with HCC receiving LT were retro- spectively analyzed and various clinicopathologic risk factors for neoplasm recurrence and survival were evaluated by univariate and multivariate analysis.Results The follow-up time ranged from 1 to 32 months.The recurrence rate was 37.3% and the mortality was 35.5%.The 12-,18-,24-month survival rate was 84.55%,70.30% and 62.24%,respectively.The 12-,18-,24-month neoplasm free survival rate was 69.05%,66.93% and 61.38%,respectively.In the univariate analysis,por- tal vein neoplasm thrombus(PVTT),Milan-criteria,neoplasm size,histological differentiation and pTNM stage were associated significantly with neoplasm recurrence,and PVTT,Milan-criteria,pre- operative alpha-fetoprotein(AFP),histological differentiation and pTNM stage were associated signif- icantly with survival rate;In the multivariate Logistic regression analysis,PVTT and histological dif- ferentiation were independent predictive factors of neoplasm recurrence,and multivariate Cox regres- sion analysis showed that PVTT and AFP independently associated with prognosis.Conclusions PVTT and histological differentiation are the most important predictive factors of neoplasm recur- rence,and PVTT and AFP independently predict the survival of patients undergoing LT.