Liver transplantation is considered as the most effective treatment for end-stage liver disease.However,serious complications still exist,particularly in two aspects:ischemia and subsequent reperfusion of the liver,ca...Liver transplantation is considered as the most effective treatment for end-stage liver disease.However,serious complications still exist,particularly in two aspects:ischemia and subsequent reperfusion of the liver,causing postoperative hepatic dysfunction and even failure;and acute and chronic graft rejections,affecting the allograft survival.Heme oxygenase(HO),a stressresponse protein,is believed to exert a protective function on both the development of ischemia-reperfusion injury(IRI) and graft rejection.In this review of current researches on allograft protection,we focused on the HO-1.We conjecture that HO-1 may link these two main factors affecting the prognosis of liver transplantations.In this review,the following aspects were emphasized:the basic biological functions of HO-1,itsroles in IRI and allograft rejection,as well as methods to induce HO-1 and the prospects of a therapeutic application of HO-1 in liver transplantation.展开更多
BACKGROUND: Blockade interaction between CD28 and B7 with CTLA4Ig has been shown to induce experimental transplantation tolerance. In order to prolong the inhibitory effect of CTLA4Ig, a recombinant adeno-associated v...BACKGROUND: Blockade interaction between CD28 and B7 with CTLA4Ig has been shown to induce experimental transplantation tolerance. In order to prolong the inhibitory effect of CTLA4Ig, a recombinant adeno-associated virus vector pSNAV expressing CTLA4Ig was constructed, and its effects on transplanted liver allografts were investigated. METHODS: The pSNAV-CTLA4Ig construct was infused into partial liver allografts of rats via the portal vein during transplantation. CTLA4Ig expression in the transplanted livers was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Furthermore, real-time quantitative PCR was used to measure the expression of IL-2, IFN-gamma, IL-4 and IL-10 in the allografts. RESULTS: The expression of CTLA4Ig in the partial allograft was detected successfully and pSNAV-CTLA4Ig improved the survival rate of rats after liver transplantation. Agarose gel analysis of RT-PCR products indicated the presence of CTLA4Ig in the pSNAV-CTLA4Ig treatment group. Cytokines expressed in allografts on day 7 after orthotopic liver transplantation showed that IL-2, IFN-gamma, IL-4 and IL-10 mRNA levels decreased in transplant recipients treated with pSNAV-CTLA4Ig compared with those treated with pSNAV-LacZ (1.62 +/- 0.09,1.52 +/- 0.11,1.50 +/- 0.07 and 1.43 +/- 0.07 versus 1.29 +/- 0.09, 1.32 +/- 0.07, 1.34 +/- 0.06 and 1.35 +/- 0.04, respectively). CONCLUSIONS: pSNAV-CTLA4Ig effectively expressed CTLA4Ig in liver allografts. CTLA4Ig improved the pathological findings after liver transplantation. CTLA4Ig induced immune tolerance of liver transplantation, and the mechanism involved induced alteration of Th1 and Th2 cytokine transcripts. The adeno-associated virus vector encoding CTLA4Ig may be useful in the clinical study of transplantation tolerance.展开更多
Starting from December 2019 the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has extended in the entire world giving origin to a pandemic.Although the respiratory system is the main apparatus involved by...Starting from December 2019 the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has extended in the entire world giving origin to a pandemic.Although the respiratory system is the main apparatus involved by the infection,several other organs may suffer coronavirus disease 2019(COVID-19)-related injuries.The human tissues expressing angiotensin-converting enzyme 2(ACE2)are all possible targets of viral damage.In fact myocarditis,meningo-encephalitis,acute kidney injury and other complications have been described with regard to SARS-CoV-2 infection.The liver has a central role in the body homeostasis contributing to detoxification,catabolism and also synthesis of important factor such as plasma proteins.ACE2 is significantly expressed just by cholangiocytes within the liver,however transaminases are increased in more than one third of COVID-19 patients,at hospital admission.The reasons for liver impairment in the course of this infection are not completely clear at present and multiple factors such as:Direct viral effect,release of cytokines,ischemic damage,use of hepatotoxic drugs,sepsis,and others,may contribute to damage.While COVID-19 seems to elicit just a transient alteration of liver function tests in subjects with normal hepatic function,of concern,more severe sequelae are frequently observed in patients with a reduced hepatic reserve.In this review we report data regarding SARS-CoV-2 infection in subjects with normal or diseased liver.In addition the risks of COVID-19 in immunosuppressed patients(either transplanted or suffering for autoimmune liver diseases)are also described.展开更多
The value of color Doppler flow imaging (CDFI) and intravenous contrast-enhanced ultrasound (CEUS) for assessing the transplanted liver and early diagnosing complications by examining hemodynamic changes was discu...The value of color Doppler flow imaging (CDFI) and intravenous contrast-enhanced ultrasound (CEUS) for assessing the transplanted liver and early diagnosing complications by examining hemodynamic changes was discussed. Seventy-five patients with orthotopic liver transplantation (OLT) underwent CDFI. The following parameters were measured: peak systolic velocity (PS), resistance index (RI) and Doppler perfusion index (DPI) of the hepatic artery (HA), time average velocity (TAV) of portal vein (PV) and velocity of hepatic vein (HV) in different stages postoperation, And 11 patients of them received CEUS. Thirty healthy subjects were enrolled as controls, The results showed that: (1) In 23 patients without obvious complications, TAV of PV within 15 days post-operation was significantly higher than in controls (P〈0.05), PS and DPI of HA within 7 days postoperation were lower, but RI was higher than in controls (P〈0.05); (2) When the hepatic artery thrombosis (HAT) occurred, PS and DPI of HA were obviously decreased, but TAV of PV significantly increased like a high saw-tooth wave; (3) While rejection occurred, both TAV of PV and PS of HA were decreased with the increase in RI of HA, and the triphasic wave of HV disappeared and displayed as saw-tooth wave; (4) The incidence of biliary complications in liver transplantation was increased when DPI was reduced; (5) Seven cases of hepatic carcinoma relapse after OLT demonstrated hyperecho in the arterial phase and hypoecho in the portal and later phase on CEUS; (6) In 2 cases of HA thrombus, there was no visualized enhancement in arterial phase of CEUS, but enhancement during the portal vein and parenchymal phase. It was concluded that the hemodynamic changes of PV, HA and HV in the transplanted liver are valuable for assessing the transplanted liver and early diagnosing complications on CDFI and CEUS.展开更多
BACKGROUND: A simultaneously transplanted liver shields a bowel graft from immunologic attack in small animals, while the possible immuno-tolerance induced by the liver in liver and small bowel transplantation (LSBT) ...BACKGROUND: A simultaneously transplanted liver shields a bowel graft from immunologic attack in small animals, while the possible immuno-tolerance induced by the liver in liver and small bowel transplantation (LSBT) is uncertain in large animal models. To investigate the clinically suspected beneficial effect of the liver on small bowel allograft, we developed a new model of composite LSBT in the pig. METHODS: Seventy outbred long-white pigs were randomized into four groups. LSBT without immunosuppressive treatment (n=10, group A); LSBT with routine immunosuppressive treatment (n=10, group B); LSBT with a lower dose of immunosuppressive treatment (n=10, group C); and small bowel segment allotransplantation without immunosuppressive treatment (n=10, group D). RESULTS: There was no remarkable difference in survival time between groups A and D (10.33 vs. 12.89 days, P>0.05), but the initial time of acute rejection of the intestinal graft in group A was clearly delayed when compared to group D (8.22 vs. 4.33 days, P<0.05), and the rejection scores in group A were remarkably lower than those in group D at each postoperative time point (0 vs. 0.44 on day 3, P<0.05; 0.22 vs. 1.78 on day 5, P<0.05; 1.11 vs. 2.56 on day 7, P<0.05). There were evident differences in postoperative survival time, initial time of acute rejection and postoperative rejection scores between groups A, B and C. Postoperative survival time (30.00 vs. 28.13 days, P>0.05), initial acute rejection time (25.40 vs. 22.13 days, P>0.05) or rejection score did not differ between groups B and C within one postoperative month. CONCLUSIONS: Compared to isolated segment small bowel allotransplantation, the intestinal graft in LSBT (group A) had a delayed initial time of acute rejection and a lower postoperative acute rejection score, and a lower dose of immunosuppressive treatment led to persistent graft immuno-tolerance in LSBT. Thus the simultaneously transplanted liver graft may reduce the risk of intestinal rejection and protect the bowel graft from severe acute rejection.展开更多
BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children.Immunization strategies to prevent vaccine-preventable infecti...BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children.Immunization strategies to prevent vaccine-preventable infections(VPIs)can effectively minimize this infection burden.However,data on age-appropriate immunization and VPIs in children after liver transplant in Asia are limited.AIM To evaluate the immunization status,VPIs and non-VPIs requiring hospitalization in children who have undergone a liver transplant.METHODS The medical records of children who had a liver transplant between 2004 and 2018 at King Chulalongkorn Memorial Hospital(Bangkok,Thailand)were retrospectively reviewed.Immunization status was evaluated via their vaccination books.Hospitalization for infections that occurred up to 5 years after liver transplantation were evaluated,and divided into VPIs and non-VPIs.Hospitalizations for cytomegalovirus and Epstein-Barr virus were excluded.Severity of infection,length of hospital stay,ventilator support,intensive care unit requirement,and mortality were assessed.RESULTS Seventy-seven children with a mean age of 3.29±4.17 years were included in the study,of whom 41(53.2%)were female.The mean follow-up duration was 3.68±1.45 years.Fortyeight children(62.3%)had vaccination records.There was a significant difference in the proportion of children with incomplete vaccination according to Thailand’s Expanded Program on Immunization(52.0%)and accelerated vaccine from Infectious Diseases Society of America(89.5%)(P<0.001).Post-liver transplant,47.9%of the children did not catch up with ageappropriate immunizations.There were 237 infections requiring hospitalization during the 5 years of follow-up.There were no significant differences in hospitalization for VPIs or non-VPIs in children with complete and incomplete immunizations.The risk of serious infection was high in the first year after receiving a liver transplant,and two children died.Respiratory and gastrointestinal systems were common sites of infection.The most common pathogens that caused VPIs were rotavirus,influenza virus,and varicella-zoster virus.CONCLUSION Incomplete immunization was common pre-and post-transplant,and nearly all children required hospitalization for non-VPIs or VPIs within 5 years posttransplant.Infection severity was high in the first year post-transplant.展开更多
OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain rea...OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4^+ and CD8^+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients. RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not deteeted in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4^+ and CD8^+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4^+ and CD8^+ T cells from the stable survivors after liver transplantation. CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent irmmune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.展开更多
AIM:To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for he...AIM:To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified as minimal, mild, moderate or severe. RESULTS: HBV recurred in 7/42 (16.6%) patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients (7.1%), minimal/non-specific changes were observed in 18 (64.2%), and at least 1 biopsy showed CH in the remaining 8 (28.5%). Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg+ or HBsAg- liver diseases.CONCLUSION: Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.展开更多
AIM: To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS: Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipient...AIM: To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS: Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS: After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy (10%) had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection.The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION: The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.展开更多
Cytomegalovirus (CMV) infection is a common complication of liver transplantationin children. The CMV serostatus of recipients and donors is theprimary risk factor, and prophylaxis or pre-emptive strategies are recomm...Cytomegalovirus (CMV) infection is a common complication of liver transplantationin children. The CMV serostatus of recipients and donors is theprimary risk factor, and prophylaxis or pre-emptive strategies are recommendedfor high-risk patients. Graft rejection, coinfection and Epstein-Bar virusreactivation, which can lead to post-transplant lymphoproliferative disease, areindirect effects of CMV infection. Assessment of CMV infection viral load shouldbe routinely performed upon clinical suspicion. However, tissue-invasive CMVdisease is not associated with CMV viraemia and requires confirmation by tissuepathology. Oral valganciclovir and intravenous ganciclovir are equivalenttreatments, and the duration of treatment depends on factors including CMV viralload, tissue pathology, and clinical response. Risk stratification by donor andrecipient status prior to transplantation and post-transplantation antiviralprophylaxis or pre-emptive therapy are recommended. Adult guidelines havebeen established but additional study of the effectiveness of the preventiveguidelines in children is needed. This review summarizes the burden, risk factors,clinical manifestations, laboratory evaluation, treatment, and prevention of CMVinfection in children after liver transplantation.展开更多
Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. ...Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Antitumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.展开更多
AIM:To evaluate the efficacy of granulocyte colony stimulating factors(G-CSF)in liver transplanted patients with hepatitis C(HCV)recurrence and Pegylated-IFN α-2b induced neutropenia,and to evaluate the impact of G-C...AIM:To evaluate the efficacy of granulocyte colony stimulating factors(G-CSF)in liver transplanted patients with hepatitis C(HCV)recurrence and Pegylated-IFN α-2b induced neutropenia,and to evaluate the impact of G-CSF administration on virological response. METHODS:Sixty-eight patients undergoing antiviral treatment for post-liver transplantation(OLT)HCV recurrence were enrolled.All patients developing neutropenia received G-CSF. RESULTS:Twenty three(34%)received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc(range 400-750/mmc);after 1 mo of G-CSF it increased to 1210/mmc(range 300-5590/mmc) (P<0.0001).Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation,infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis(P<0.003). CONCLUSION:G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasingneutrophil count,prolonging treatment and leading to sustained virological response(SVR)rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.展开更多
Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of ev...Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.展开更多
The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary chola...The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.展开更多
Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its...Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.U...Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.展开更多
Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome corona...Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.展开更多
Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,...Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.展开更多
Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)funct...Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.展开更多
Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipien...Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.展开更多
基金Supported by The grants for Young Scientist Project,National Natural Science Foundation of China,No.30600598"Qi Ming Star for Young Scientist"Project,Science and Technology Commission of Shanghai Municipality,No.10QH1401800+3 种基金"Shu Guang Scholar"Project,Shanghai Municipal Educational Commission,No.10SG20Research and Innovation Project of Shanghai Municipal Education Commission,Project No.09YZ103the Key Medical Project of Science and Technology Commission of Shanghai Municipality,No.09411952500Nano-specific Project of Science and Technology Commission of Shanghai Municipality,Project No.0952nm03800
文摘Liver transplantation is considered as the most effective treatment for end-stage liver disease.However,serious complications still exist,particularly in two aspects:ischemia and subsequent reperfusion of the liver,causing postoperative hepatic dysfunction and even failure;and acute and chronic graft rejections,affecting the allograft survival.Heme oxygenase(HO),a stressresponse protein,is believed to exert a protective function on both the development of ischemia-reperfusion injury(IRI) and graft rejection.In this review of current researches on allograft protection,we focused on the HO-1.We conjecture that HO-1 may link these two main factors affecting the prognosis of liver transplantations.In this review,the following aspects were emphasized:the basic biological functions of HO-1,itsroles in IRI and allograft rejection,as well as methods to induce HO-1 and the prospects of a therapeutic application of HO-1 in liver transplantation.
文摘BACKGROUND: Blockade interaction between CD28 and B7 with CTLA4Ig has been shown to induce experimental transplantation tolerance. In order to prolong the inhibitory effect of CTLA4Ig, a recombinant adeno-associated virus vector pSNAV expressing CTLA4Ig was constructed, and its effects on transplanted liver allografts were investigated. METHODS: The pSNAV-CTLA4Ig construct was infused into partial liver allografts of rats via the portal vein during transplantation. CTLA4Ig expression in the transplanted livers was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Furthermore, real-time quantitative PCR was used to measure the expression of IL-2, IFN-gamma, IL-4 and IL-10 in the allografts. RESULTS: The expression of CTLA4Ig in the partial allograft was detected successfully and pSNAV-CTLA4Ig improved the survival rate of rats after liver transplantation. Agarose gel analysis of RT-PCR products indicated the presence of CTLA4Ig in the pSNAV-CTLA4Ig treatment group. Cytokines expressed in allografts on day 7 after orthotopic liver transplantation showed that IL-2, IFN-gamma, IL-4 and IL-10 mRNA levels decreased in transplant recipients treated with pSNAV-CTLA4Ig compared with those treated with pSNAV-LacZ (1.62 +/- 0.09,1.52 +/- 0.11,1.50 +/- 0.07 and 1.43 +/- 0.07 versus 1.29 +/- 0.09, 1.32 +/- 0.07, 1.34 +/- 0.06 and 1.35 +/- 0.04, respectively). CONCLUSIONS: pSNAV-CTLA4Ig effectively expressed CTLA4Ig in liver allografts. CTLA4Ig improved the pathological findings after liver transplantation. CTLA4Ig induced immune tolerance of liver transplantation, and the mechanism involved induced alteration of Th1 and Th2 cytokine transcripts. The adeno-associated virus vector encoding CTLA4Ig may be useful in the clinical study of transplantation tolerance.
文摘Starting from December 2019 the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has extended in the entire world giving origin to a pandemic.Although the respiratory system is the main apparatus involved by the infection,several other organs may suffer coronavirus disease 2019(COVID-19)-related injuries.The human tissues expressing angiotensin-converting enzyme 2(ACE2)are all possible targets of viral damage.In fact myocarditis,meningo-encephalitis,acute kidney injury and other complications have been described with regard to SARS-CoV-2 infection.The liver has a central role in the body homeostasis contributing to detoxification,catabolism and also synthesis of important factor such as plasma proteins.ACE2 is significantly expressed just by cholangiocytes within the liver,however transaminases are increased in more than one third of COVID-19 patients,at hospital admission.The reasons for liver impairment in the course of this infection are not completely clear at present and multiple factors such as:Direct viral effect,release of cytokines,ischemic damage,use of hepatotoxic drugs,sepsis,and others,may contribute to damage.While COVID-19 seems to elicit just a transient alteration of liver function tests in subjects with normal hepatic function,of concern,more severe sequelae are frequently observed in patients with a reduced hepatic reserve.In this review we report data regarding SARS-CoV-2 infection in subjects with normal or diseased liver.In addition the risks of COVID-19 in immunosuppressed patients(either transplanted or suffering for autoimmune liver diseases)are also described.
文摘The value of color Doppler flow imaging (CDFI) and intravenous contrast-enhanced ultrasound (CEUS) for assessing the transplanted liver and early diagnosing complications by examining hemodynamic changes was discussed. Seventy-five patients with orthotopic liver transplantation (OLT) underwent CDFI. The following parameters were measured: peak systolic velocity (PS), resistance index (RI) and Doppler perfusion index (DPI) of the hepatic artery (HA), time average velocity (TAV) of portal vein (PV) and velocity of hepatic vein (HV) in different stages postoperation, And 11 patients of them received CEUS. Thirty healthy subjects were enrolled as controls, The results showed that: (1) In 23 patients without obvious complications, TAV of PV within 15 days post-operation was significantly higher than in controls (P〈0.05), PS and DPI of HA within 7 days postoperation were lower, but RI was higher than in controls (P〈0.05); (2) When the hepatic artery thrombosis (HAT) occurred, PS and DPI of HA were obviously decreased, but TAV of PV significantly increased like a high saw-tooth wave; (3) While rejection occurred, both TAV of PV and PS of HA were decreased with the increase in RI of HA, and the triphasic wave of HV disappeared and displayed as saw-tooth wave; (4) The incidence of biliary complications in liver transplantation was increased when DPI was reduced; (5) Seven cases of hepatic carcinoma relapse after OLT demonstrated hyperecho in the arterial phase and hypoecho in the portal and later phase on CEUS; (6) In 2 cases of HA thrombus, there was no visualized enhancement in arterial phase of CEUS, but enhancement during the portal vein and parenchymal phase. It was concluded that the hemodynamic changes of PV, HA and HV in the transplanted liver are valuable for assessing the transplanted liver and early diagnosing complications on CDFI and CEUS.
基金supported by a grant from the National Natural Science Foundation of China(30872484)
文摘BACKGROUND: A simultaneously transplanted liver shields a bowel graft from immunologic attack in small animals, while the possible immuno-tolerance induced by the liver in liver and small bowel transplantation (LSBT) is uncertain in large animal models. To investigate the clinically suspected beneficial effect of the liver on small bowel allograft, we developed a new model of composite LSBT in the pig. METHODS: Seventy outbred long-white pigs were randomized into four groups. LSBT without immunosuppressive treatment (n=10, group A); LSBT with routine immunosuppressive treatment (n=10, group B); LSBT with a lower dose of immunosuppressive treatment (n=10, group C); and small bowel segment allotransplantation without immunosuppressive treatment (n=10, group D). RESULTS: There was no remarkable difference in survival time between groups A and D (10.33 vs. 12.89 days, P>0.05), but the initial time of acute rejection of the intestinal graft in group A was clearly delayed when compared to group D (8.22 vs. 4.33 days, P<0.05), and the rejection scores in group A were remarkably lower than those in group D at each postoperative time point (0 vs. 0.44 on day 3, P<0.05; 0.22 vs. 1.78 on day 5, P<0.05; 1.11 vs. 2.56 on day 7, P<0.05). There were evident differences in postoperative survival time, initial time of acute rejection and postoperative rejection scores between groups A, B and C. Postoperative survival time (30.00 vs. 28.13 days, P>0.05), initial acute rejection time (25.40 vs. 22.13 days, P>0.05) or rejection score did not differ between groups B and C within one postoperative month. CONCLUSIONS: Compared to isolated segment small bowel allotransplantation, the intestinal graft in LSBT (group A) had a delayed initial time of acute rejection and a lower postoperative acute rejection score, and a lower dose of immunosuppressive treatment led to persistent graft immuno-tolerance in LSBT. Thus the simultaneously transplanted liver graft may reduce the risk of intestinal rejection and protect the bowel graft from severe acute rejection.
基金Supported by Thai Pediatric Gastroenterology,Hepatology and Immunology Research Unit,King Chulalongkorn Memorial Hospital,Faculty of Medicine,Chulalongkorn UniversityThe 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship,Chulalongkorn Universityand the Thailand Research Fund Thailand Science Research and Innovation,No.MRG6280190.
文摘BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children.Immunization strategies to prevent vaccine-preventable infections(VPIs)can effectively minimize this infection burden.However,data on age-appropriate immunization and VPIs in children after liver transplant in Asia are limited.AIM To evaluate the immunization status,VPIs and non-VPIs requiring hospitalization in children who have undergone a liver transplant.METHODS The medical records of children who had a liver transplant between 2004 and 2018 at King Chulalongkorn Memorial Hospital(Bangkok,Thailand)were retrospectively reviewed.Immunization status was evaluated via their vaccination books.Hospitalization for infections that occurred up to 5 years after liver transplantation were evaluated,and divided into VPIs and non-VPIs.Hospitalizations for cytomegalovirus and Epstein-Barr virus were excluded.Severity of infection,length of hospital stay,ventilator support,intensive care unit requirement,and mortality were assessed.RESULTS Seventy-seven children with a mean age of 3.29±4.17 years were included in the study,of whom 41(53.2%)were female.The mean follow-up duration was 3.68±1.45 years.Fortyeight children(62.3%)had vaccination records.There was a significant difference in the proportion of children with incomplete vaccination according to Thailand’s Expanded Program on Immunization(52.0%)and accelerated vaccine from Infectious Diseases Society of America(89.5%)(P<0.001).Post-liver transplant,47.9%of the children did not catch up with ageappropriate immunizations.There were 237 infections requiring hospitalization during the 5 years of follow-up.There were no significant differences in hospitalization for VPIs or non-VPIs in children with complete and incomplete immunizations.The risk of serious infection was high in the first year after receiving a liver transplant,and two children died.Respiratory and gastrointestinal systems were common sites of infection.The most common pathogens that caused VPIs were rotavirus,influenza virus,and varicella-zoster virus.CONCLUSION Incomplete immunization was common pre-and post-transplant,and nearly all children required hospitalization for non-VPIs or VPIs within 5 years posttransplant.Infection severity was high in the first year post-transplant.
文摘OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4^+ and CD8^+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients. RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not deteeted in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4^+ and CD8^+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4^+ and CD8^+ T cells from the stable survivors after liver transplantation. CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent irmmune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.
文摘AIM:To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified as minimal, mild, moderate or severe. RESULTS: HBV recurred in 7/42 (16.6%) patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients (7.1%), minimal/non-specific changes were observed in 18 (64.2%), and at least 1 biopsy showed CH in the remaining 8 (28.5%). Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg+ or HBsAg- liver diseases.CONCLUSION: Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.
基金Supported by Fundación Manchega de Investigación y Docencia en Gastroenterología and partially by Red Nacional en Investigatión de Hepatología y Gastroenterología (RNIHG)Dr. Moraleda was supported by a grant from the Ministerio de Educación y Ciencia (Programa Ramón y Cajal)
文摘AIM: To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS: Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS: After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy (10%) had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection.The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION: The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.
文摘Cytomegalovirus (CMV) infection is a common complication of liver transplantationin children. The CMV serostatus of recipients and donors is theprimary risk factor, and prophylaxis or pre-emptive strategies are recommendedfor high-risk patients. Graft rejection, coinfection and Epstein-Bar virusreactivation, which can lead to post-transplant lymphoproliferative disease, areindirect effects of CMV infection. Assessment of CMV infection viral load shouldbe routinely performed upon clinical suspicion. However, tissue-invasive CMVdisease is not associated with CMV viraemia and requires confirmation by tissuepathology. Oral valganciclovir and intravenous ganciclovir are equivalenttreatments, and the duration of treatment depends on factors including CMV viralload, tissue pathology, and clinical response. Risk stratification by donor andrecipient status prior to transplantation and post-transplantation antiviralprophylaxis or pre-emptive therapy are recommended. Adult guidelines havebeen established but additional study of the effectiveness of the preventiveguidelines in children is needed. This review summarizes the burden, risk factors,clinical manifestations, laboratory evaluation, treatment, and prevention of CMVinfection in children after liver transplantation.
文摘Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Antitumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.
文摘AIM:To evaluate the efficacy of granulocyte colony stimulating factors(G-CSF)in liver transplanted patients with hepatitis C(HCV)recurrence and Pegylated-IFN α-2b induced neutropenia,and to evaluate the impact of G-CSF administration on virological response. METHODS:Sixty-eight patients undergoing antiviral treatment for post-liver transplantation(OLT)HCV recurrence were enrolled.All patients developing neutropenia received G-CSF. RESULTS:Twenty three(34%)received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc(range 400-750/mmc);after 1 mo of G-CSF it increased to 1210/mmc(range 300-5590/mmc) (P<0.0001).Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation,infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis(P<0.003). CONCLUSION:G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasingneutrophil count,prolonging treatment and leading to sustained virological response(SVR)rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.
文摘Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.
文摘The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.
文摘Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.
文摘Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.
基金the National Natural Science Foundation of China(82103662).
文摘Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.
文摘Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
基金supported by grants from the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0148)the National Natural Science Foundation of China (82170666 and 81873592)Chongqing Research Program of Technological Innovation and Application Demonstration (cstc2021jscx-gksbX0060)
文摘Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.
基金supported by grants from the National Nat-ural Science Foundation of China (81570587 and 81700557)the Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007 and 2017B030314018)+3 种基金Guangdong Provincial Natural Science Funds for Major Basic Science Culture Project (2015A030308010)Science and Technology Program of Guangzhou (201704020150)the Natural Science Foundations of Guangdong province (2016A030310141 and 2020A1515010091)Young Teachers Training Project of Sun Yat-sen University (K0401068) and the Guangdong Science and Technology Innovation Strategy (pdjh2022b0010 and pdjh2023a0002)。
文摘Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.