Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present wit...Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation.LT is also performed in metabolic disorders for end-stage liver disease,its sequelae including hepatocellular cancer.It is also performed for preventing metabolic crisis’,arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia.Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis,cholestasis,inflammation,variable amount of fibrosis,and cirrhosis.The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT.A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters.Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver.The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.展开更多
Macrovesicular Steatosis(MS)is an independent risk factor for adverse post-liver transplant(LT)outcomes.The degree of MS is intimately related to the viability of the liver graft,which in turn is crucial to the succes...Macrovesicular Steatosis(MS)is an independent risk factor for adverse post-liver transplant(LT)outcomes.The degree of MS is intimately related to the viability of the liver graft,which in turn is crucial to the success of the operation.An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT.While a formal liver biopsy is the goldstandard diagnostic test for MS,given the logistical and time constraints it is not universally feasible.Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy.Hence,the development of an accurate,non-invasive,easy-to-use,handheld,real-time device for quantification of MS would fill this lacuna in the deceased donor selection process.We present the hypothesis,design and proof-ofconcept of a study,which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.展开更多
The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. ...The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. We present a case of early allograft dysfunction following deceased donor liver transplantation(DDLT) where plasmapheresis was effective as a bridge to recovery and possibly avoiding a retransplantation. A 16 years old boy, known to have decompensated Wilson's disease underwent DDLT at our Public Sector Hospital. He received a healthy liver from a brain-dead donor, whose liver was considered too large for the boy. The graft was reduced in situ to a left lobe graft. Surgery was uneventful and the recipient was well for the initial 96 h. On Doppler and further computed tomography scan, a partial portal vein thrombus was noted. He was reexplored and a Fogarty endothombecteomy was performed. Following the second surgery, he developed severe allograft dysfunction with a peak bilirubin of 40 mg/d L. He underwent imaging to rule out technical causes for the dysfunction, followed by a liver biopsy, which revealed acute cellular rejection. Multiple cycles of plasmapheresis were initiated. Over the next two weeks, the graft demonstrated a gradual recovery. He was discharged on the 30 th postoperative day, with a serum bilirubin of 5.5 mg/d L. He remains well on follow-up, with the liver function tests improving further. Our report demonstrates the beneficial effect of plasmapheresis, which appears to be an effective treatment option for early allograft dysfunction following liver transplantation and may obviate the need for retransplantation.展开更多
Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree.There is a wide geographical variation with regards to its incidence,and risk-factor associati...Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree.There is a wide geographical variation with regards to its incidence,and risk-factor associations which may include liver fluke infection,primary sclerosing cholangitis,and hepatolithiasis amongst others.These tumours are classified into intrahepatic,perihilar and distal based on their anatomical location.Morphologically,intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants.Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas.Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions.While clinical characteristics and management of these tumours have been extensively elucidated in literature,their ultra-structure and tumour biology remain relatively unknown.This review focuses on the current knowledge of pathological characteristics,molecular alterations of cholangiocarcinoma,and its precursor lesions(including biliary intraepithelial neoplasia,intraductal papillary neoplasms of the bile duct,intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).展开更多
Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and im...Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.展开更多
Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor,graft and recipient factors.Within the cohort of patients waiting for a transplant,better matching of t...Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor,graft and recipient factors.Within the cohort of patients waiting for a transplant,better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation.A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age,gender,ethnicity,viral serology;graft factors such as size and quality,recipient factors such as age,size,gender and transplant factors such as major or minor blood group incompatibility and immunological factors.We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’clinical experience.Multiple donor and recipient factors impact graft survival after liver transplantation.Appropriate matching based on donor-organ-recipient variables,modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.展开更多
Post-coronavirus disease 2019(COVID-19)cholangiopathy(PCC)is a rare but lifethreatening complication of COVID-19 infection.PCC typically presents when patients recovering from the contagion and manifests as cholestasi...Post-coronavirus disease 2019(COVID-19)cholangiopathy(PCC)is a rare but lifethreatening complication of COVID-19 infection.PCC typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver disease.The pathogenesis of PCC is little understood.Hepatic injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for cholangiocytes.Though PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients,it is considered as a separate and unique entity in the literature.Various treatment options like ursodeoxycholic acid,steroids,plasmapheresis,and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited success.We have noticed significant improvement in liver function with antiplatelet therapy in a couple of patients.PCC can progress to end-stage liver disease necessitating liver transplantation.In this article,we discuss the current knowledge of PCC focusing on its pathophysiology,clinical manifestations,and management strategies.展开更多
Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,s...Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.展开更多
The coronavirus pandemic(COVID-19)has had an unprecedented effect on various disease processes and their management.COVID-19 is likely to have a complex pathophysiological interplay with the post-transplant patients;o...The coronavirus pandemic(COVID-19)has had an unprecedented effect on various disease processes and their management.COVID-19 is likely to have a complex pathophysiological interplay with the post-transplant patients;one affecting the clinical course and outcome of the other.In the absence of validated data from trials,there is strong dependence on experience based on previous similar epidemics(SARS/MERS),and from consensus based on expert opinions.Despite the fact that our knowledge is rapidly evolving with time,there still is relatively limited objective data on the effect of COVID-19 on the human body.Numerous questions remain unanswered,one of which involves the management of immunosuppression in the post-transplant recipient during this contagion.The core tenet of which continues to be that of establishing an equipoise between infection and rejection.This review summarises the current knowledge on immune interactions of the virus,the immunomodulatory effects that may be at play,and its relation to the art of immunosuppression.展开更多
Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,...Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,for management of hepatitis B reactivation.She developed bleeding diathesis and severe thrombocytopenia was detected on investigations.Bone marrow examination showed normocellular marrow with megakaryocytes.Tenofovir was stopped and she was started on intravenous immunoglobulin,followed by steroids.There was improvement in platlet counts.The case highlights a rare side effect of tenofovir therapy.展开更多
文摘Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation.LT is also performed in metabolic disorders for end-stage liver disease,its sequelae including hepatocellular cancer.It is also performed for preventing metabolic crisis’,arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia.Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis,cholestasis,inflammation,variable amount of fibrosis,and cirrhosis.The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT.A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters.Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver.The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.
文摘Macrovesicular Steatosis(MS)is an independent risk factor for adverse post-liver transplant(LT)outcomes.The degree of MS is intimately related to the viability of the liver graft,which in turn is crucial to the success of the operation.An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT.While a formal liver biopsy is the goldstandard diagnostic test for MS,given the logistical and time constraints it is not universally feasible.Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy.Hence,the development of an accurate,non-invasive,easy-to-use,handheld,real-time device for quantification of MS would fill this lacuna in the deceased donor selection process.We present the hypothesis,design and proof-ofconcept of a study,which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.
文摘The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. We present a case of early allograft dysfunction following deceased donor liver transplantation(DDLT) where plasmapheresis was effective as a bridge to recovery and possibly avoiding a retransplantation. A 16 years old boy, known to have decompensated Wilson's disease underwent DDLT at our Public Sector Hospital. He received a healthy liver from a brain-dead donor, whose liver was considered too large for the boy. The graft was reduced in situ to a left lobe graft. Surgery was uneventful and the recipient was well for the initial 96 h. On Doppler and further computed tomography scan, a partial portal vein thrombus was noted. He was reexplored and a Fogarty endothombecteomy was performed. Following the second surgery, he developed severe allograft dysfunction with a peak bilirubin of 40 mg/d L. He underwent imaging to rule out technical causes for the dysfunction, followed by a liver biopsy, which revealed acute cellular rejection. Multiple cycles of plasmapheresis were initiated. Over the next two weeks, the graft demonstrated a gradual recovery. He was discharged on the 30 th postoperative day, with a serum bilirubin of 5.5 mg/d L. He remains well on follow-up, with the liver function tests improving further. Our report demonstrates the beneficial effect of plasmapheresis, which appears to be an effective treatment option for early allograft dysfunction following liver transplantation and may obviate the need for retransplantation.
文摘Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree.There is a wide geographical variation with regards to its incidence,and risk-factor associations which may include liver fluke infection,primary sclerosing cholangitis,and hepatolithiasis amongst others.These tumours are classified into intrahepatic,perihilar and distal based on their anatomical location.Morphologically,intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants.Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas.Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions.While clinical characteristics and management of these tumours have been extensively elucidated in literature,their ultra-structure and tumour biology remain relatively unknown.This review focuses on the current knowledge of pathological characteristics,molecular alterations of cholangiocarcinoma,and its precursor lesions(including biliary intraepithelial neoplasia,intraductal papillary neoplasms of the bile duct,intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).
文摘Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.
文摘Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor,graft and recipient factors.Within the cohort of patients waiting for a transplant,better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation.A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age,gender,ethnicity,viral serology;graft factors such as size and quality,recipient factors such as age,size,gender and transplant factors such as major or minor blood group incompatibility and immunological factors.We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’clinical experience.Multiple donor and recipient factors impact graft survival after liver transplantation.Appropriate matching based on donor-organ-recipient variables,modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.
文摘Post-coronavirus disease 2019(COVID-19)cholangiopathy(PCC)is a rare but lifethreatening complication of COVID-19 infection.PCC typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver disease.The pathogenesis of PCC is little understood.Hepatic injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for cholangiocytes.Though PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients,it is considered as a separate and unique entity in the literature.Various treatment options like ursodeoxycholic acid,steroids,plasmapheresis,and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited success.We have noticed significant improvement in liver function with antiplatelet therapy in a couple of patients.PCC can progress to end-stage liver disease necessitating liver transplantation.In this article,we discuss the current knowledge of PCC focusing on its pathophysiology,clinical manifestations,and management strategies.
文摘Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.
文摘The coronavirus pandemic(COVID-19)has had an unprecedented effect on various disease processes and their management.COVID-19 is likely to have a complex pathophysiological interplay with the post-transplant patients;one affecting the clinical course and outcome of the other.In the absence of validated data from trials,there is strong dependence on experience based on previous similar epidemics(SARS/MERS),and from consensus based on expert opinions.Despite the fact that our knowledge is rapidly evolving with time,there still is relatively limited objective data on the effect of COVID-19 on the human body.Numerous questions remain unanswered,one of which involves the management of immunosuppression in the post-transplant recipient during this contagion.The core tenet of which continues to be that of establishing an equipoise between infection and rejection.This review summarises the current knowledge on immune interactions of the virus,the immunomodulatory effects that may be at play,and its relation to the art of immunosuppression.
文摘Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,for management of hepatitis B reactivation.She developed bleeding diathesis and severe thrombocytopenia was detected on investigations.Bone marrow examination showed normocellular marrow with megakaryocytes.Tenofovir was stopped and she was started on intravenous immunoglobulin,followed by steroids.There was improvement in platlet counts.The case highlights a rare side effect of tenofovir therapy.
