Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these pati...Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients.The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.Methods:The data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed.These patients were divided into the sirolimus group[patients took sirolimus combined with calcineurin inhibitors(CNIs)(n=125)]and non-sirolimus group[patients took CNI-based therapy without sirolimus(n=68)].Recurrence-free survival(RFS)and overall survival(OS)were compared between the two groups.The prognostic factors and independent risk factors for RFS and OS were further evaluated.Results:Non-sirolimus was an independent risk factor for RFS(HR=2.990;95%CI:1.050-8.470;P=0.040)and OS(HR=3.100;95%CI:1.190-8.000;P=0.020).A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group(69.6%vs.80.9%,P=0.030).Compared with the non-sirolimus group,the sirolimus group had significantly better RFS(P<0.001)and OS(P<0.001).Further subgroup analysis showed similar results.Conclusions:This study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.展开更多
Background:The effectiveness and safety of marginal donor livers remain controversial.This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation(LT).Methods:T...Background:The effectiveness and safety of marginal donor livers remain controversial.This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation(LT).Methods:This study included 199 liver donors(including 16 split donors)and 206 liver recipients from January 1,2018 to January 27,2020,with case follow-up until July 31,2021.Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers.Indices of liver and kidney functions,complications,and survival curves of the two groups were compared.Results:Compared with the standard donor group,the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation(P<0.05);there were no significant differences in alanine aminotransferase,aspartate aminotransferase,and total bilirubin levels after LT(all P>0.05);there was no significant difference in the incidence of complications after LT(P>0.05);there was also no significant difference in the survival curve(P=0.335).Conclusions:There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups.The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.展开更多
Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancrea...Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.展开更多
Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a...Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.展开更多
BACKGROUND Ischemia-reperfusion injury(IRI) is a major risk associated with liver surgery and transplantation,and its pathological mechanism is complex.Interleukin-1 receptor antagonist(IL-1ra) can protect the liver f...BACKGROUND Ischemia-reperfusion injury(IRI) is a major risk associated with liver surgery and transplantation,and its pathological mechanism is complex.Interleukin-1 receptor antagonist(IL-1ra) can protect the liver from IRI.However,the regulatory mechanism of IL-1ra expression is still unclear.AIM To identify the mechanism that could protect the liver in the early stage of IRI.METHODS To screen the key genes in hepatic IRI,we performed RNA sequencing and gene enrichment analysis on liver tissue from mice with hepatic IRI.Subsequently,we verified the expression and effect of IL-1ra in hepatic IRI.We also used promoter mutagenesis and chromatin immunoprecipitation assay to search for the transcriptional regulatory sites of hypoxia-inducible factor(HIF)-1α.Finally,to explore the protective mechanism of ischemic preconditioning(IP),we examined the expression of HIF-1α and IL-1ra after IP.RESULTS We identified IL-1ra as a key regulator in hepatic IRI.The expression of IL-1ra was significantly upregulated after hepatic IRI both in vivo and in vitro.Furthermore,we found that HIF-1αregulated Il-1ra transcription in response to hypoxia.Increased HIF-1α accumulation promoted IL-1ra expression,whereas inhibition of HIF-1α exhibited the opposite effect.We also confirmed a predominant role for hypoxia response element in the regulation of Il1ra transcription by HIF-1αactivation.Of note,we demonstrated that IP protects against hepatic IRI by inducing IL-1ra expression,which is mediated through HIF-1α.CONCLUSION We demonstrated that ischemia or hypoxia leads to increased expression of IL-1ra through HIF-1α.Importantly,IP protects the liver from IRI via the HIF-1α–IL-1ra pathway.展开更多
To the Editor:During the ongoing coronavirus disease 2019(COVID-19)pan-demic globally,patients with chronic liver diseases(CLD),par-ticularly cirrhosis,hepatobiliary malignancies,candidates for liver transplantation(L...To the Editor:During the ongoing coronavirus disease 2019(COVID-19)pan-demic globally,patients with chronic liver diseases(CLD),par-ticularly cirrhosis,hepatobiliary malignancies,candidates for liver transplantation(LT),and immunosuppressed LT recipients appear to be at increased risk of infections,which leads to an increase in mortality[1-6].Apart from physical distancing,quarantine and isolation,vaccination is crucial for the restraining of the epidemic and the protection from severe acute respiratory syndrome coron-avirus 2(SARS-CoV-2)infection and aggravation of COVID-19[7,8].A recent prospective,multicenter,open-label study in China has demonstrated the safety of inactivated whole-virion SARS-CoV-2 vaccines in patients with CLD.展开更多
Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipie...Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.展开更多
基金supported by a grant from Post-Doctoral Applied Research Project of Qingdao City(RZ2000002871)。
文摘Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients.The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.Methods:The data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed.These patients were divided into the sirolimus group[patients took sirolimus combined with calcineurin inhibitors(CNIs)(n=125)]and non-sirolimus group[patients took CNI-based therapy without sirolimus(n=68)].Recurrence-free survival(RFS)and overall survival(OS)were compared between the two groups.The prognostic factors and independent risk factors for RFS and OS were further evaluated.Results:Non-sirolimus was an independent risk factor for RFS(HR=2.990;95%CI:1.050-8.470;P=0.040)and OS(HR=3.100;95%CI:1.190-8.000;P=0.020).A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group(69.6%vs.80.9%,P=0.030).Compared with the non-sirolimus group,the sirolimus group had significantly better RFS(P<0.001)and OS(P<0.001).Further subgroup analysis showed similar results.Conclusions:This study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.
基金supported by a grant from the start-up fund for scientific research of high-level talents in the Affiliated Hospital of Qingdao University(3631)。
文摘Background:The effectiveness and safety of marginal donor livers remain controversial.This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation(LT).Methods:This study included 199 liver donors(including 16 split donors)and 206 liver recipients from January 1,2018 to January 27,2020,with case follow-up until July 31,2021.Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers.Indices of liver and kidney functions,complications,and survival curves of the two groups were compared.Results:Compared with the standard donor group,the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation(P<0.05);there were no significant differences in alanine aminotransferase,aspartate aminotransferase,and total bilirubin levels after LT(all P>0.05);there was no significant difference in the incidence of complications after LT(P>0.05);there was also no significant difference in the survival curve(P=0.335).Conclusions:There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups.The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.
基金Supported by National Natural Science Foundation of China,No.81400680Tianjin Natural Science Foundation,No.17JCQNJC12800
文摘Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.
基金Supported by National Natural Science Foundation of China,No.81400680the National High Technology Research and Development Program of China,No.2012 AA021001
文摘Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.
基金the National Natural Science Foundation of China,No.81670600.
文摘BACKGROUND Ischemia-reperfusion injury(IRI) is a major risk associated with liver surgery and transplantation,and its pathological mechanism is complex.Interleukin-1 receptor antagonist(IL-1ra) can protect the liver from IRI.However,the regulatory mechanism of IL-1ra expression is still unclear.AIM To identify the mechanism that could protect the liver in the early stage of IRI.METHODS To screen the key genes in hepatic IRI,we performed RNA sequencing and gene enrichment analysis on liver tissue from mice with hepatic IRI.Subsequently,we verified the expression and effect of IL-1ra in hepatic IRI.We also used promoter mutagenesis and chromatin immunoprecipitation assay to search for the transcriptional regulatory sites of hypoxia-inducible factor(HIF)-1α.Finally,to explore the protective mechanism of ischemic preconditioning(IP),we examined the expression of HIF-1α and IL-1ra after IP.RESULTS We identified IL-1ra as a key regulator in hepatic IRI.The expression of IL-1ra was significantly upregulated after hepatic IRI both in vivo and in vitro.Furthermore,we found that HIF-1αregulated Il-1ra transcription in response to hypoxia.Increased HIF-1α accumulation promoted IL-1ra expression,whereas inhibition of HIF-1α exhibited the opposite effect.We also confirmed a predominant role for hypoxia response element in the regulation of Il1ra transcription by HIF-1αactivation.Of note,we demonstrated that IP protects against hepatic IRI by inducing IL-1ra expression,which is mediated through HIF-1α.CONCLUSION We demonstrated that ischemia or hypoxia leads to increased expression of IL-1ra through HIF-1α.Importantly,IP protects the liver from IRI via the HIF-1α–IL-1ra pathway.
基金the"Clinic+X"of the Affiliated Hospital of Qingdao University(No.3754)Social Sci-ence Popularization and Application Research Project of Shandong Province(No.2021-SKZC-18).
文摘To the Editor:During the ongoing coronavirus disease 2019(COVID-19)pan-demic globally,patients with chronic liver diseases(CLD),par-ticularly cirrhosis,hepatobiliary malignancies,candidates for liver transplantation(LT),and immunosuppressed LT recipients appear to be at increased risk of infections,which leads to an increase in mortality[1-6].Apart from physical distancing,quarantine and isolation,vaccination is crucial for the restraining of the epidemic and the protection from severe acute respiratory syndrome coron-avirus 2(SARS-CoV-2)infection and aggravation of COVID-19[7,8].A recent prospective,multicenter,open-label study in China has demonstrated the safety of inactivated whole-virion SARS-CoV-2 vaccines in patients with CLD.
基金supported by grants from the National S&T Major Project (2017ZX10203205)Key Program,National Natural Science Foundation of China (81930016)Zhejiang Provincial Natural Science Foundation of China (LY21H160026)。
文摘Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.
