Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach

BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT.METHODS A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1,2022,and May 31,2023.The study included 25 SLT cases and 81 whole liver transplantation(WLT)cases.Total ex-vivo liver splitting was employed for SLT graft procurement in three steps.Patient outcomes were determined,including liver function parameters,postoperative complications,and perioperative mortality.Group comparisons for categorical variables were performed using theχ²-test.RESULTS In the study,postoperative complications in the 25 SLT cases included hepatic artery thrombosis(n=1)and pulmonary infections(n=3),with no perioperative mortality.In contrast,among the 81 patients who underwent WLT,complications included perioperative mortality(n=1),postoperative pulmonary infections(n=8),abdominal infection(n=1),hepatic artery thromboses(n=3),portal vein thrombosis(n=1),and intra-abdominal bleeding(n=5).Comparative analysis demonstrated significant differences in alanine aminotransferase(176.0 vs 73.5,P=0.000)and aspartate aminotransferase(AST)(42.0 vs 29.0,P=0.004)at 1 wk postoperatively,and in total bilirubin(11.8 vs 20.8,P=0.003)and AST(41.5 vs 26.0,P=0.014)at 2 wk postoperatively.However,the overall incidence of complications was comparable between the two groups(P>0.05).CONCLUSION Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach,especially under the expertise of an experienced transplant center.The approach developed by our center can serve as a valuable reference for other transplantation centers.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT(ABOi-LT)is unknown.AIM To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with endstage liver disease(ESLD).METHODS We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT.The pretransplantation HIV viral load was undetectable,with no active opportunistic infections.Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses,followed by an intraoperative regimen of intravenous immunoglobulin,methylprednisolone,and basiliximab.Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil,and prednisone.RESULTS At the intermediate-term follow-up,patients showed undetectable HIV viral load,CD4(+)T cell counts greater than 150 cells/μL,no HBV recurrence,and stable liver function.A liver allograft biopsy showed no evidence of acute cellular rejection.Both patients survived at 36-42 mo of follow-up.CONCLUSION This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes,suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

Prognostic value of ultrasound in early arterial complications post liver transplant

Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].

Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma:A comprehensive review

The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

Tailored classification of portal vein thrombosis for liver transplantation:Focus on strategies for portal vein inflow reconstruction

Portal vein thrombosis(PVT)is currently not considered a contraindication for liver transplantation(LT),but diffuse or complicated PVT remains a major surgical challenge.Here,we review the prevalence,natural course and current grading systems of PVT and propose a tailored classification of PVT in the setting of LT.PVT in liver transplant recipients is classified into three types,corresponding to three portal reconstruction strategies:Anatomical,physiological and non-physiological.Type I PVT can be removed via low dissection of the portal vein(PV)or thrombectomy;porto-portal anastomosis is then performed with or without an interposed vascular graft.Physiological reconstruction used for type II PVT includes vascular interposition between mesenteric veins and PV,collateral-PV and splenic vein-PV anastomosis.Non-physiological reconstruction used for type III PVT includes cavoportal hemitransposition,renoportal anastomosis,portal vein arterialization and multivisceral transplantation.All portal reconstruction techniques were reviewed.This tailored classification system stratifies PVT patients by surgical complexity,risk of postoperative complications and long-term survival.We advocate using the tailored classification for PVT grading before LT,which will urge transplant surgeons to make a better preoperative planning and pay more attention to all potential strategies for portal reconstruction.Further verification in a large-sample cohort study is needed.

Immunotherapy in liver transplantation for hepatocellular carcinoma:Pros and cons

Liver transplantation(LT)has emerged as a curative strategy for hepatocellular carcinoma(HCC),but contributes to a higher predisposition to HCC recurrence in the immunosuppression context,especially for tumors beyond the Milan criteria.Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors,including HCC,it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection.Nevertheless,accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC,from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting.Generally,immunotherapy mainly includes immune checkpoint inhibitors(ICIs),adoptive cell transfer(ACT)and vaccine therapy.ICIs,followed by ACT,have been most investigated in LT,with some promising results.Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy,it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients.In addition,the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT.In this review,we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC.Moreover,we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.

Topological approach of liver segmentation based on 3D visualization technology in surgical planning for split liver transplantation

BACKGROUND Split liver transplantation(SLT)is a complex procedure.The left-lateral and right tri-segment splits are the most common surgical approaches and are based on the Couinaud liver segmentation theory.Notably,the liver surface following right trisegment splits may exhibit different degrees of ischemic changes related to the destruction of the local portal vein blood flow topology.There is currently no consensus on preoperative evaluation and predictive strategy for hepatic segmental necrosis after SLT.AIM To investigate the application of the topological approach in liver segmentation based on 3D visualization technology in the surgical planning of SLT.METHODS Clinical data of 10 recipients and 5 donors who underwent SLT at Shenzhen Third People’s Hospital from January 2020 to January 2021 were retrospectively analyzed.Before surgery,all the donors were subjected to 3D modeling and evaluation.Based on the 3D-reconstructed models,the liver splitting procedure was simulated using the liver segmentation system described by Couinaud and a blood flow topology liver segmentation(BFTLS)method.In addition,the volume of the liver was also quantified.Statistical indexes mainly included the hepatic vasculature and expected volume of split grafts evaluated by 3D models,the actual liver volume,and the ischemia state of the hepatic segments during the actual surgery.RESULTS Among the 5 cases of split liver surgery,the liver was split into a left-lateral segment and right trisegment in 4 cases,while 1 case was split using the left and right half liver splitting.All operations were successfully implemented according to the preoperative plan.According to Couinaud liver segmentation system and BFTLS methods,the volume of the left lateral segment was 359.00±101.57 mL and 367.75±99.73 mL,respectively,while that measured during the actual surgery was 397.50±37.97 mL.The volume of segment IV(the portion of ischemic liver lobes)allocated to the right tri-segment was 136.31±86.10 mL,as determined using the topological approach to liver segmentation.However,during the actual surgical intervention,ischemia of the right tri-segment section was observed in 4 cases,including 1 case of necrosis and bile leakage,with an ischemic liver volume of 238.7 mL.CONCLUSION 3D visualization technology can guide the preoperative planning of SLT and improve accuracy during the intervention.The simulated operation based on 3D visualization of blood flow topology may be useful to predict the degree of ischemia in the liver segment and provide a reference for determining whether the ischemic liver tissue should be removed during the surgery.

Two case reports and literature review for hepatic epithelioid angiomyolipoma: Pitfall of misdiagnosis

BACKGROUND Hepatic epithelioid angiomyolipoma(HEAML) is a rare liver disease and is easily misdiagnosed. Enhanced recognition of HEAML is beneficial to the differential diagnosis of rare liver diseases.CASE SUMMARY We presented two cases of HEAML in Changzheng Hospital, Naval Medical University, and then collected and analyzed all reports about HEAML recorded in PubMed, MEDLINE, China Science Periodical Database, and VIP database from January 2000 to March 2018. A total of 409 cases of HEAML in 97 reports were collected, with a ratio of men to women of 1:4.84 and an age range from 12 years to 80 years(median 44 years). Among the patients with clinical symptoms mentioned, 61.93%(205/331) were asymptomatic, 34.74%(115/331) showed upper or right upper quadrant abdomen discomfort, while a few of them showed abdominal mass, gastrointestinal symptoms, low fever, or weight loss. The misdiagnosis rate of HEAML was as high as 40.34%(165/409) due to its nonspecific imaging findings. Most of the tumors were solitary and round in morphology, with clear boundaries. Ultrasound scan indicated low echo with internal nonuniformity and rich blood supply in most cases. Computer tomography/magnetic resonance imaging enhanced scan showed varied characteristics. The ratio of fast wash-in and fast wash-out, fast wash-in and slow wash-out, and delayed enhancement was roughly 4:5:1. A definite diagnosis of HEAML depended on the pathological findings of the epithelioid cells in lesions and the expression of human melanoma black 45, smooth muscle actin,melanoma antigen, and actin by immunohistochemical staining. HEAML had a relatively low malignant rate of 3.91%. However, surgical resection was the main treatment for HEAML, due to the difficulty diagnosing before operation.CONCLUSION HEAML is a rare and easily misdiagnosed disease, and it should be diagnosed carefully, taking into account clinical course, imaging, pathological,and immunohistochemical findings.

Clinical practice guidelines on liver transplantation for hepatocellular carcinoma in China(2018 edition)

Introduction Over 300000 people in China die each year of hepatocellular carcinoma(HCC),which accounts for approximately half of HCCrelated deaths worldwide.Liver transplantation(LT)is generally recognized as one of the most effective therapeutic approaches for end-stage liver diseases.Since the beginning of the second LT boom in the 1990s,LT in China has been developed rapidly with professional and large-scale trends,and it is approaching or has reached the level of developed countries in terms of quantity and quality.According to the China Liver Transplant Registry,the number of transplants for HCC accounted for 36.8%of the total number of LT cases during the past 5 years in the mainland of China.In order to develop an effective,safe and standardized protocol to guide the national LT practice,the clinical guidelines of LT for HCC was launched in 2014 by multidisciplinary experts from Chinese Society of Organ Transplantation,Chinese Medical Association and Chinese Association of Organ Transplantation,Chinese Medical Doctor Association.Recently,there have been new clinical and scientific advances in the field of LT and to keep abreast of these achievements,the original clinical practice guidelines need to be updated.

Reconstructing the portal vein through a posterior pancreatic tunnel:New choice for portal vein thrombosis during liver transplantation

BACKGROUND Thrombectomy and anatomical anastomosis(TAA)has long been considered the optimal approach to portal vein thrombosis(PVT)in liver transplantation(LT).However,TAA and the current approach for non-physiological portal reconstructions are associated with a higher rate of complications and mortality in some cases.AIM To describe a new choice for reconstructing the portal vein through a posterior pancreatic tunnel(RPVPPT)to address cases of unresectable PVT.METHODS Between August 2019 and August 2021,245 adult LTs were performed.Forty-five(18.4%)patients were confirmed to have PVT before surgery,among which seven underwent PV reconstruction via the RPVPPT approach.We retrospectively analyzed the surgical procedure and postoperative complications of these seven recipients that underwent PV reconstruction due to PVT.RESULTS During the procedure,PVT was found in all the seven cases with significant adhesion to the vascular wall and could not be dissected.The portal vein proximal to the superior mesenteric vein was damaged in one case when attempting thrombolectomy,resulting in massive bleeding.LT was successfully performed in all patients with a mean duration of 585 min(range 491-756 min)and mean intraoperative blood loss of 800 mL(range 500-3000 mL).Postoperative complications consisted of chylous leakage(n=3),insufficient portal venous flow to the graft(n=1),intra-abdominal hemorrhage(n=1),pulmonary infection(n=1),and perioperative death(n=1).The remaining six patients survived at 12-17 mo follow-up.CONCLUSION The RPVPPT technique might be a safe and effective surgical procedure during LT for complex PVT.However,follow-up studies with large samples are still warranted due to the relatively small number of cases.

Two-in-one:A pooled analysis of primary hepatic neuroendocrine carcinoma combine d/collide d with hepatocellular carcinoma

To the Editor:Primary hepatic neuroendocrine carcinoma(PHNEC)combined/collided with hepatocellular carcinoma(HCC)is a rare and intriguing disease with characteristics of two histologically different cancers.Usually,a combined type refers to the cases in which hepatic neuroendocrine carcinoma(HNEC)and HCC components intermingle with each other and cannot be clearly separated in the transitional areas,while a collision type refers to those in which the two distinct cancers occurred simultaneously and independently.Sometimes it is difficult to readily distinguish these two types.We searched PubMed,Medline,China Science Periodical Database,and VIP Database with the publication from January 1980 to January 2019,using the keywords(“hepatic neuroendocrine carcinoma”or“HNEC”)and(“hepatocellular carcinoma”or“HCC”).After manually excluding records on secondary HNEC and other types of liver cancer,a total of 28 cases in 24 reports[1–24]were identified and summarized in Table 1.

Immunometabolic inflammation and hepatocellular carcinoma

To the Editor: Inflammation-cancer transformation and metabolomics are hot topics in hepatocellular carcinoma (HCC). Cancer-related inflammation and anti-cancer immunity co-exist in cancer progression and the microenvironmental conditions dictate the direction [1].

Liver resection versus liver transplantation for hepatocellular carcinoma within the Milan criteria based on estimated microvascular invasion risks

Background:Preoperative prediction of microvascular invasion(MVI)in hepatocellular carcinoma(HCC)may optimize individualized treatment decision-making.This study aimed to investigate the prognostic differences between HCC patients undergoing liver resection(LR)and liver transplantation(LT)based on predicted MVI risks.Methods:We analysed 905 patients who underwent LR,including 524 who underwent anatomical resection(AR)and 117 who underwent LT for HCC within the Milan criteria using propensity score matching.A nomogram model was used to predict preoperative MVI risk.Results:The concordance indices of the nomogram for predicting MVI were 0.809 and 0.838 in patients undergoing LR and LT,respectively.Based on an optimal cut-off value of 200 points,the nomogram defined patients as high-or low-risk MVI groups.LT resulted in a lower 5-year recurrence rate and higher 5-year overall survival(OS)rate than LR among the high-risk patients(23.6%vs 73.2%,P<0.001;87.8%vs 48.1%,P<0.001)and low-risk patients(19.0%vs 45.7%,P<0.001;86.5%vs 70.0%,P=0.002).The hazard ratios(HRs)of LT vs LR for recurrence and OS were 0.18(95%confidence interval[CI],0.09–0.37)and 0.12(95%CI,0.04–0.37)among the high-risk patients and 0.37(95%CI,0.21–0.66)and 0.36(95%CI,0.17–0.78)among the low-risk patients.LT also provided a lower 5-year recurrence rate and higher 5-year OS rate than AR among the high-risk patients(24.8%vs 63.5%,P=0.001;86.7%vs 65.7%,P=0.004),with HRs of LT vs AR for recurrence and OS being 0.24(95%CI,0.11–0.53)and 0.17(95%CI,0.06–0.52),respectively.The 5-year recurrence and OS rates between patients undergoing LT and AR were not significantly different in the low-risk patients(19.4%vs 28.3%,P=0.129;85.7%vs 77.8%,P=0.161).Conclusions:LT was superior to LR for patients with HCC within the Milan criteria with a predicted high or low risk of MVI.No significant differences in prognosis were found between LT and AR in patients with a low risk of MVI.

Primary hepatic squamous cell carcinoma with abdominal incision metastasis after hepatectomy

To the Editor:Primary hepatic squamous cell carcinoma(PHSCC)is a rare and easily misdiagnosed disease.We reported a PHSCC case with abdominal incision metastasis after hepatectomy,and reviewed the clinical course,imaging,pathology and immunohistochemical findings.Our case may provide a better understanding of PHSCC.

Clinical practice guideline on liver transplantation for hepatocellular carcinoma in China(2021 edition)

Hepatocellular carcinoma(HCC)is the main cause of cancer-related deaths in adult men under the age of 60 years in China.^([1])Liver transplantation(LT)is generally recognized as one of the most effective therapeutic approaches for end-stage liver diseases.LT guidelines for HCC were firstly launched in 2014 and were updated in 2018.Recently,further updates are required to adapt to the new situation of LT in China and to continue advancing the recommendations.(Full version in Supplementary file,http://links.lww.com/CM9/B362).