Impact of treatment modalities on patients with recurrent hepatocellular carcinoma after liver transplantation:Preliminary experience

Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.

Hepatic arterial anastomosis in adult liver transplantation

Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liver[1,2].Complex arterial reconstruction has been identified as a crucial risk factor for arterial thrombosis[1–5].Consequently,selecting the appropriate arterial reconstruction method to decrease hepatic artery thrombosis has garnered the attention of the surgical community.

Alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis:Preliminary experience

Background:Portal vein tumor thrombosis(PVTT)is regarded as a contraindication for liver transplantation(LT)in hepatocellular carcinoma(HCC).However,some of these patients may have a favorable prognosis after LT.In this study,we evaluated the biological behavior of HCC with PVTT using tumor biomarker(alpha-fetoprotein,AFP)and 18 F-FDG positron emission tomography(tumor standard uptake value)to identify a subset of patients who may be suitable for LT.Methods:Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were analyzed.Different pre-transplant prognostic factors were identified by univariate and multivariate analyses.PVTT status was identified following Vp classification(Vp1-Vp4).Results:Three-year recurrence-free survival and overall survival rates were 40%and 65.4%in Vp2-Vp3 PVTT patients,21.4%and 30.6%in Vp4 PVTT patients(P<0.05).Total tumor diameter>8 cm,pretransplant AFP level>1000 ng/m L and intrahepatic tumor maximal standard uptake value(SUVmaxtumor>5)were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT patients.Low risk patients were defined as total tumor diameter≤8 cm;or if total tumor diameter more than 8 cm,with both pre-transplant AFP level less than 1000 ng/m L and intrahepatic tumor SUVmax less than 5,simultaneously.Twenty-two Vp2-3 PVTT HCC patients(46.8%)were identified as low risk patients,and their 3-year recurrence-free and overall survival rates were 67.6%and 95.2%,respectively.Conclusions:Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18 F-FDG SUVmax might be suitable for LT.

Three-dimensional modeling in complex liver surgery and liver transplantation

Liver resection and transplantation are the most effective therapies for many hepatobiliary tumors and diseases.However,these surgical procedures are challenging due to the anatomic complexity and many anatomical variations of the vascular and biliary structures.Three-dimensional(3D)printing models can clearly locate and describe blood vessels,bile ducts and tumors,calculate both liver and residual liver volumes,and finally predict the functional status of the liver after resection surgery.The 3D printing models may be particularly helpful in the preoperative evaluation and surgical planning of especially complex liver resection and transplantation,allowing to possibly increase resectability rates and reduce postoperative complications.With the continuous developments of imaging techniques,such models are expected to become widely applied in clinical practice.

Liver transplantation for intrahepatic and perihilar cholangiocarcinoma: Current and future

Cholangiocarcinomas are categorized as intrahepatic cholangio- carcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), and dis- tal cholangiocarcinoma (dCCA) [1] . iCCA and pCCA are the second most common primary hepatobiliary malignant neoplasms [ 1 , 2 ]. Most patients with iCCA and pCCA have asymptomatic clinical course, highly aggressive nature and dismal prognosis [3] . Com- plete surgical resection offers the best possibility of long-term sur- vival but only a minority of patients are amenable to R0 resec- tion [4] . Tumor involvement of segmental bilateral intrahepatic bile duct, inadequate remnant liver volume or hepatic functional reserve due to underlying chronic liver disease, are key factors limiting the resectability of iCCA and pCCA. Liver transplantation (LT) provides an option for patients with unresectable iCCA and pCCA [4] .

New Algorithm Rules Out Acute-on-chronic Liver Failure Development within 28 Days from Acute Decompensation of Cirrhosis

Background and Aims:Approximately 10%of patients with acute decompensated(AD)cirrhosis develop acute-on-chronic liver failure(ACLF)within 28 days.Such cases have high mortality and are difficult to predict.Therefore,we aimed to establish and validate an algorithm to identify these patients on hospitalization.Methods:Hospitalized patients with AD who developed ACLF within 28 days were considered pre-ACLF.Organ dysfunction was defined accord-ing to the chronic liver failure-sequential organ failure as-sessment(CLIF-SOFA)criteria,and proven bacterial infec-tion was taken to indicate immune system dysfunction.A retrospective multicenter cohort and prospective one were used to derive and to validate the potential algorithm,re-spectively.A miss rate of<5%was acceptable for the calcu-lating algorithm to rule out pre-ACLF.Results:In the deri-vation cohort(n=673),46 patients developed ACLF within 28 days.Serum total bilirubin,creatinine,international normalized ratio,and present proven bacterial infection at admission were associated with the development of ACLF.AD patients with≥2 organ dysfunctions had a higher risk for pre-ACLF patients[odds ratio=16.58195%confidence interval:(4.271-64.363),p<0.001].In the derivation co-hort,67.5%of patients(454/673)had≤1 organ dysfunction and two patients(0.4%)were pre-ACLF,with a miss rate of 4.3%(missed/total,2/46).In the validation cohort,65.9%of patients(914/1388)had≤1 organ dysfunction,and four(0.3%)of them were pre-ACLF,with a miss rate of 3.4%(missed/total,4/117).Conclusions:AD patients with≤1 organ dysfunction had a significantly lower risk of developing ACLF within 28 days of admission and could be safely ruled out with a pre-ACLF miss rate of<5%.

Investigation on the short-term outcome and prognostic impact of predisposition,and precipitants in inpatients with chronic liver disease from Chinese AcuTe on CHronic LIver FailurE(CATCH-LIFE)cohorts

Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.Methods:The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies(NCT02457637 and NCT03641872)conducted in highly endemic hepatitis B virus(HBV)areas.Competing risk analysis was used to evaluate the effect of predispositions,including the etiology and severity of CLDs and precipitants;on sequential 28,90,and 365-day liver transplantation(LT)-free mortality.Results:Among all enrolled patients,76.8%of adverse outcomes(including death and LT)within one year occurred within 90 days.Compared with alcoholic etiology,the association of HBV etiology with poorer outcomes was remarkably on the 28th day(hazard ratio[HR],1.81;95%confidence interval[CI],1.07-3.06;p=0.026);however,and dimin-ished or became insignificant at 90 days and 365 days.Cirrhosis increased the adjusted risk for 365-day(HR,1.50;CI,1.13-1.99;p=0.004)LT-free mortality when compared with noncirrhosis.In patients with cirrhosis,prior decompensation(PD)independently increased the adjusted risk of 365-day LT-free mortality by 1.25-fold(p=0.021);however,it did not increase the risk for 90-day mortality.Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90-day LT-free mortality.Conclusions:The 90-day outcome should be considered a significant endpoint for evaluating the short-term prognosis of hospitalized patients with CLD.Predisposing factors,other than etiology,mainly affected the delayed(365-day)outcome.Timely effective therapy for CLD etiology,especially antiviral treatments for HBV,and post-discharge long-term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.

Portal inflow reconstruction for liver transplantation with portal vein thrombosis

Complex non-malignant portal vein thrombosis(PVT),defined as Yerdel grade 4,was previously considered as a contraindication for liver transplantation(LT)because of technical challenges followed by high morbidity and mortality(1).In complex PVT,Bhangui et al.proposed defining reconstruction of portal inflow as physiological when the splanchnic venous blood can be redirected to the graft,thus resolving the pre-existing portal hypertension(PHT)(2).Renoportal anastomosis(RPA)and coronary-portal anastomosis(CPA)are 2 main options(3).However,all reports were single case reports or small case series regarding physiological reconstruction for complex PVT,therefore,the postoperative outcomes were very heterogeneous.Herein,we introduced our experience of physiological portal inflow restoration for liver transplant in complex PVT patients,and outcomes were compared with those of patients with non-complex PVT.