Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis.

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.

Influence of socioeconomic factors on liver transplant survival outcomes in patients with autoimmune liver disease in the United States.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs): autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) have different survival outcomes after liver transplant (LT). Outcomes are influenced by factors including disease burden, medical comorbidities, and socioeconomic variables. MATERIALS AND METHODS: Using the United Network for Organ Sharing database (UNOS), we identified 13,702 patients with AILDs listed for LT between 2002 and 2021. Outcomes of interest were waitlist removal, post-LT patient survival, and post- LT graft survival. A stepwise multivariate analysis was performed adjusting for transplant recipient gender, race, diabetes mellitus, model for end-stage liver disease (MELD) score, and additional social determinants including the presence of education, reliance on public insurance, working for income, and U.S. citizenship status. RESULTS: Lack of college education and having public insurance increased the risk of waitlist removal (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.09; 95 % CI, 1.00-1.18; respectively), and negatively influenced post-LT patient survival (HR, 1.16; 95 % CI, 1.06-1.26, and HR, 1.15; 95 % CI, 1.06-1.25; respectively) and graft survival (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.15; 95 % CI, 1.06-1.25; respectively). Not working for income proved to have the greatest detrimental impact on both patient survival (HR, 1.41; 95 % CI, 1.24-1.6) and graft survival (HR, 1.21; 95 % CI, 1.09-1.35). CONCLUSIONS: Our study highlights that lack of college education and public insurance have a detrimental impact on waitlist mortality, patient survival, and graft survival. Not working for income negatively affects post-LT survival outcomes. Not having U.S. citizenship does not affect survival outcomes in AILDs patients.

Waitlist mortality in patients with autoimmune liver diseases.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis are the primary indication for ∼24% of total liver transplants. The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease and it often underestimates the severity of autoimmune liver diseases. We aim to compare the rate of adverse waitlist removal among patients with all autoimmune liver diseases and other indications for liver transplant in the Model for End-Stage Liver -Na era. MATERIALS AND METHODS: Using the United Network for Organ Sharing database, we identified all patients listed for liver transplant from 2016 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to evaluate the waitlist survival. RESULTS: Patients with autoimmune hepatitis had a higher risk of being removed from the waitlist for death or clinical deterioration (SHR 1.37, 95% CI 1.08-1.72; P<0.007), followed by primary biliary cholangitis (SHR 1.34, 95% CI 1.07-1.68; P<0.011). CONCLUSIONS: High waitlist death or removal for clinical deterioration was observed in patients with PBC and AIH when compared to other etiologies. It may be useful to reassess the process of awarding MELD exception points to mitigate such disparity.

Successful pregnancy and follow-up after in vitro fertilization of a kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and hypothyroidism.

This report describes the case of a female kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and postsurgical hypothyroidism due to Grave's disease who had a healthy newborn after in vitro fertilization (IVF). Cases of successful pregnancy involving women who underwent IVF after kidney transplantation have been reported. Normal and stable renal function, adequate immunosuppressant therapy, and well-managed blood pressure are requirements to be eligible for IVF and pregnancy. Primary biliary cholangitis without cirrhosis does not seem to worsen during pregnancy and IVF must be individualized in patients with systemic lupus erythematosus. There are no similar case reports involving kidney transplant patients or individuals with autoimmune disorders, so the decision to perform IVF had to be individualized in order to avoid complications for the mother and fetus.

LIVER TRANSPLANTATION FOR BILE DUCT INJURY AFTER CHOLECYSTECTOMY.

BACKGROUND: Bile duct injury is a life-threatening complication that requires proper management to prevent the onset of negative outcomes. Patients may experience repeated episodes of cholangitis, secondary biliary cirrhosis, end-stage liver disease and death. OBJECTIVE: To report a single center experience in iatrogenic secondary liver transplantation after cholecystectomy and review the literature. METHODS: This was a retrospective single center study. Of the 1662 liver transplantation realized, 10 (0.60 %) were secondary to iatrogenic bile ducts injuries due cholecystectomies. Medical records of these patients were reviewed in this study. RESULTS: Nine of 10 patients were women; the median time in waiting list and between cholecystectomy and inclusion in waiting list was of 222 days and of 139.9 months, respectively. Cholecystectomy was performed by open approach in eight (80%) cases and by laparoscopic approach in two (20%) cases. The patients underwent an average of 3.5 surgeries and procedures before liver transplantation. Biliary reconstruction was realized with a Roux-en-Y hepaticojejunostomy in nine (90%) cases. Mean operative time was 447.2 minutes and the median red blood cell transfusion was 3.4 units per patient. Mortality in the first month was of 30%. CONCLUSION: Although the liver transplantation is an extreme treatment for an initially benign disease, it has its well-defined indications in treatment of bile duct injuries after cholecystectomy, either in acute or chronic scenario.

Transplante de fígado para tratamento de lesão de via biliar após colecistectomia / Liver transplantation for bile duct injury after cholecystectomy

ABSTRACT BACKGROUND: Bile duct injury is a life-threatening complication that requires proper management to prevent the onset of negative outcomes. Patients may experience repeated episodes of cholangitis, secondary biliary cirrhosis, end-stage liver disease and death. OBJECTIVE: To report a single center experience in iatrogenic secondary liver transplantation after cholecystectomy and review the literature. METHODS: This was a retrospective single center study. Of the 1662 liver transplantation realized, 10 (0.60 %) were secondary to iatrogenic bile ducts injuries due cholecystectomies. Medical records of these patients were reviewed in this study. RESULTS: Nine of 10 patients were women; the median time in waiting list and between cholecystectomy and inclusion in waiting list was of 222 days and of 139.9 months, respectively. Cholecystectomy was performed by open approach in eight (80%) cases and by laparoscopic approach in two (20%) cases. The patients underwent an average of 3.5 surgeries and procedures before liver transplantation. Biliary reconstruction was realized with a Roux-en-Y hepaticojejunostomy in nine (90%) cases. Mean operative time was 447.2 minutes and the median red blood cell transfusion was 3.4 units per patient. Mortality in the first month was of 30%. CONCLUSION: Although the liver transplantation is an extreme treatment for an initially benign disease, it has its well-defined indications in treatment of bile duct injuries after cholecystectomy, either in acute or chronic scenario.

RESUMO CONTEXTO: A lesão da via biliar é uma complicação que pode ameaçar a vida e que requer manejo adequado para prevenir o aparecimento de desfechos negativos. Os pacientes podem apresentar episódios repetidos de colangite, cirrose biliar secundária, doença hepática terminal e até mesmo morte. OBJETIVO: Avaliar a experiência de um único centro em transplante hepático secundário a lesão iatrogênica de via biliar pós-colecistectomia e fazer uma revisão de literatura. MÉTODOS: Este foi um estudo retrospectivo de um único centro. Dos 1662 transplantes de fígado, 10 (0,60%) foram secundários a lesões iatrogênicas das vias biliares devido à colecistectomias. Os prontuários médicos desses pacientes foram revisados neste estudo. RESULTADOS: Nove dos dez pacientes eram mulheres; o tempo médio em lista de espera de transplante e entre colecistectomia e inclusão na lista de espera foi de 222 dias e de 139,9 meses, respectivamente. A colecistectomia foi realizada por abordagem aberta em oito (80%) casos e por abordagem laparoscópica em dois (20%) casos. Os pacientes foram submetidos a uma média de 3,5 cirurgias e procedimentos antes do transplante de fígado e a reconstrução biliar foi realizada com hepaticojejunostomia em Y-de-Roux em nove (90%) casos. O tempo operatório médio foi de 447,2 minutos e a média de transfusão de concentrados de hemácias foi de 3,4 unidades por paciente. Mortalidade no primeiro mês foi de 30%. CONCLUSÃO: Embora o transplante de fígado seja um tratamento extremo para uma doença inicialmente benigna, ele tem suas indicações bem definidas no tratamento de lesões biliares após colecistectomia, seja em um cenário agudo ou crônico.

Occult central pontine myelinolysis post liver transplant: A consequence of pre-transplant hyponatremia.

Rapid overcorrection of chronic hyponatremia can lead to osmotic demyelination syndrome or central pontine myelinolysis (CPM), a diagnosis often triggered by observing the characteristics of neurological abnormalities developed as a result of CPM. However, anyone with chronic hyponatremia and overcorrection of serum sodium is at risk of physiological CPM despite the lack of clinical symptoms. We report an adult patient who presented as post-op delirium, had incidental finding of CPM by magnetic resonance imaging (MRI) of the head after a liver transplant. Despite his non-typical presentation, the patient had the typical risk factors of CPM such as chronic hyponatremia, rapid overcorrection of serum sodium and cirrhosis undergoing a transplant. As hyponatremia and neurological disorder such encephalopathy simultaneously affect patients with cirrhosis, CPM may be more common than once thought in the chronic liver disease population and inappropriate hyponatremia management has important medical consequences that can go unnoticed.

A 44-Year-Old Woman With Sudden Breathlessness, Tightness in Chest, and Hypotension After Extubation in the Early Postoperative Period After Liver Transplantation.

CASE PRESENTATION: A 44-year-old woman with Child-Pugh class C cirrhosis due to primary biliary cirrhosis and mild portopulmonary syndrome received a liver transplant. Her basal catheterization showed a mean pulmonary arterial pressure (mPAP) of 28 mm Hg, pulmonary artery occlusion pressure (PAOP) of 8 mm Hg, pulmonary vascular resistance (PVR) of 307 dynes.s.cm-5, and a cardiac output of 5.2 L/min. The echocardiogram did not reveal right ventricular dilatation (mid-diameter of 34 mm). In surgery, hemodynamic assessment showed an mPAP of 25 mm Hg, PAOP of 6 mm Hg, PVR of 262 dynes.s.cm-5 and cardiac output of 5.8 L/min. During the anhepatic period, the patient required norepinephrine (0.4 µg/kg/min) but had no complications during reperfusion; throughout surgery, her mPAP was never > 30 mm Hg. At the end of surgery, the brain natriuretic peptide level was 66 pg/mL (< 100 pg/mL). One day following transplantation, the patient remained hemodynamically stable and was therefore weaned from mechanical ventilation. However, 6 h following extubation, she reported breathlessness and tightness in chest, and developed sudden arterial hypotension, oxygen desaturation, and oliguria.

Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction.

BACKGROUND/PURPOSE: Biliary atresia and other liver biliary obstructions are relevant conditions in pediatric surgery due to their progression to biliary cirrhosis and indication for liver transplantation. It is known that the period during which biliary obstruction persists determines the development of cirrhosis and its reversibility after a biliary drainage procedure. However, no time or histological markers of biliary cirrhosis reversibility have been established. MATERIALS AND METHODS: One hundred and twenty-nine young Wistar rats underwent surgery for ligation of the common bile duct and were maintained until 8weeks. A part of these animals was submitted to biliary drainage surgery at 2, 3, 4, 5, or 6weeks after the initial procedure. After cyst formation at the site of obstruction, cyst-jejunal anastomosis was performed to restore bile flow. After biliary obstruction and drainage, liver samples were collected for histological and molecular analysis of the genes responsible for collagen deposition and fibrosis. RESULTS: The mortality rates were 39.8% and 56.7% after the first and second procedures, respectively. Ductular proliferation (p=0.001) and collagen deposition increased according to the period under obstruction (p=0.0001), and both alterations were partially reduced after biliary drainage. There were no significant differences in the values of desmin and α-actin according to the period during which the animal remained with biliary obstruction (p=0.09 and p=0.3, respectively), although increased values of transforming growth factor beta 1 (TGFß1) occurred after 8weeks (p=0.000). Desmin levels decreased, and α-actin and TGFß1 levels increased according to the period under obstruction. The molecular alterations were partially reversed after biliary drainage. CONCLUSIONS: The histologic and molecular changes in the liver parenchyma promoted by biliary obstruction in the young animal can be partially reversed by a biliary drainage procedure.

Intrapancreatic common hepatic artery arising from the superior mesenteric artery, a challenging anatomic variation in a multiorgan harvesting.

INTRODUCTION: Understanding abdominal vascular anatomy is crucial for multiorgan recovery. In this case report, we have described a common hepatic artery that arises from the superior mesenteric artery but follows an intrapancreatic course. METHODS: The donor was ideal for multiorgan recovery and the recipient was a 29-year-old woman awaiting a second transplant owing to primary nonfunction of her first engrafted organ. The indication for transplantation was secondary biliary cirrhosis. A type I diabetic recipient on dialysis therapy was awaiting the kidney and pancreas. RESULTS: The urgent condition of our liver recipient combined with the anatomical finding prioritized liver procurement, therefore the pancreas was discarded. CONCLUSIONS: The recognition of all anatomic variations will allow us to improve the use of the scarce resource of deceased donor organs.

Influence of biliary anastomosis on recovery from secondary biliary cirrhosis.

OBJECTIVE: The influence of choledochoduodenostomy and choledochojejunostomy on the repair of hepatic lesions secondary to biliary obstruction is not well known. The aim of the present study was to compare the effects of choledochoduodenostomy and choledochojejunostomy on the recovery of these lesions in rats with biliary obstruction. METHODS: Rats subjected to 4 weeks of biliary obstruction underwent choledochoduodenostomy (n=10) or choledochojejunostomy (n=10). The following variables were measured: total bilirubin, alkaline phosphatase, aminotransferases, and albumin. Hepatic mitochondrial energy metabolism was evaluated by calculating the respiratory control ratio and the oxidative phosphorylation index. Hepatic morphometry was used to estimate the mass of the hepatocytes, bile ducts, and fibrosis, as well as the hepatic stellate cell count. RESULTS: After choledochoduodenostomy and choledochojejunostomy, there was a regression in cholestasis and a reduction in the oxidative phosphorylation index. However, the total bilirubin, alkaline phosphatase, albumin, and respiratory control ratio values improved only after choledochojejunostomy. The mass of the liver, spleen, and fibrosis was reduced after both choledochoduodenostomy and choledochojejunostomy, but the number of hepatic stellate cells increased. After choledochojejunostomy, the hepatic mass recovered completely, and the spleen mass was significantly reduced compared with that after choledochoduodenostomy. After both choledochoduodenostomy and choledochojejunostomy, enterobiliary reflux, biliary contamination, and an exacerbation in hepatic inflammation developed. CONCLUSION: Choledochojejunostomy was more effective than choledochoduodenostomy, but both techniques induced enterobiliary reflux and biliary contamination, which may explain the maintenance of hepatic alterations, especially after choledochoduodenostomy.

[Liver disease recurrence after liver transplantation]. / Recurrencia de la enfermedad hepática primaria después del trasplante hepático.

Liver transplantation has become a standard option in the management of patients with end-stage liver disease. It is now evident that the most common etiology of long-term graft dysfunction is the recurrence of the primary liver disease. Autoimmune liver disorders such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis recur between 15 to 30% of the graft recipients. The clinical expression of this recurrence tends to be milder; the diagnosis is only established in many patients by findings in the liver biopsy. This milder clinical expression may be due to the use of immunosuppressive therapy for the prevention of organ rejection and it may also be modulating immune mechanisms that underlie these conditions. The recurrence of hepatitis C virus infection is characterized by an accelerated progression towards cirrhosis and hepatic failure due to the lack of an effective immunoprophylaxis program and an effective antiviral therapy. The recurrence of hepatitis B is uncommon due to the availability on an effective immunoprophylaxis program with effective antiviral agents. The familial amyloidotic polyneuropathy is a genetic condition residing in the hepatocyte that produces a mutation of transthyretin; this abnormal protein is deposited in peripheral nerves, gastrointestinal tract, heart, and kidneys. The liver from these patients, apart from producing this abnormal protein, is otherwise normal, and has been used as an organ for recipients in dire need of a liver transplant, such as patients with hepatocellular carcinoma. This approach is known as domino liver transplantation. As these recipients are followed long term, they may develop de novo amyloidosis. In summary, the underlying liver condition that led to endstage liver disease and liver transplantation may recur after liver transplantation. The clinical expression of the recurrence of the hepatic disease is modulated by the immunosuppression program unless we have an effective immunoprophylaxis and antiviral agents such as in hepatitis B.

Anti-parietal cell autoantibodies (PCA) in primary biliary cirrhosis: a putative marker for recurrence after orthotopic liver transplantation?

INTRODUCTION: Liver transplantation (OLT) for primary biliary cirrhosis (PBC) is characterized by disease recurrence of up to one third of patients. The diagnosis of recurrence requires a cholestatic profile and a typical histology representing a challenge for transplant hepatologists. Antimitochondrial antibodies (AMA) establish the initial diagnosis, persist after OLT, and are thus of limited value for the diagnosis of recurrence. Aim of this analysis was to identify serological parameters associated with recurrent PBC. PATIENTS AND METHODS: OLT performed between 1992 and 2006 at Hannover Medical School were evaluated retrospectively including histology before and after OLT, autoimmune serological parameters and clinical characteristics. RESULTS: Between 1992 and 2006 72 patients underwent OLT with histologically confirmed PBC. Median follow up was 123 months. AMA persisted in 55 (76%) patients. Anti-parietal cell antibodies (PCA) were detectable in 41% of the patients before and 47% after OLT. Liver biopsies were obtained in 34 patients post OLT upon clinical suspicion, and recurrent PBC diagnosed in 28% after a mean of 71 months (range 13-161). Anti-PCA were detected in 100% of patients with recurrence before and following transplantation, 54% of patients with anti-PCA before OLT developed recurrence during follow-up. There were no differences in immunosuppressive regimen. DISCUSSION: Although unspecific for the diagnosis of PBC, anti-PCA prevalence increased after OLT, and was 100% in patients with recurrent PBC. Recurrent PBC developed in 54% of patients with anti-PCA before OLT suggesting a diagnostic role of anti-PCA as a simple and cost effective marker of recurrence.

Recurrencia de la enfermedad hepática primaria después del trasplante hepático / Liver disease recurrence after liver transplantation

Liver transplantation has become a standard option in the management of patients with end-stage liver disease. It is now evident that the most common etiology of long-term graft dysfunction is the recurrence of the primary liver disease. Autoimmune liver disorders such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis recur between 15 to 30 percent of the graft recipients. The clinical expression of this recurrence tends to be milder; the diagnosis is only established in many patients by fndings in the liver biopsy. This milder clinical expression may be due to the use of immunosuppressive therapy for the prevention of organ rejection and it may also be modulating immune mechanisms that underlie these conditions. The recurrence of hepatitis C virus infection is characterized by an accelerated progression towards cirrhosis and hepatic failure due to the lack of an effective immunoprophylaxis program and an effective antiviral therapy. The recurrence of hepatitis B is uncommon due to the availability on an effective immunoprophylaxis program with effective antiviral agents. The familial amyloidotic polyneuropathy is a genetic condition residing in the hepatocyte that produces a mutation of transthyretin; this abnormal protein is deposited in peripheral nerves, gastrointestinal tract, heart, and kidneys. The liver from these patients, apart from producing this abnormal protein, is otherwise normal, and has been used as an organ for recipients in dire need of a liver transplant, such as patients with hepatocellular carcinoma. This approach is known as “domino” liver transplantation. As these recipients are followed long term, they may develop de novo amyloidosis. In summary, the underlying liver condition that led to endstage liver disease and liver transplantation may recur after liver transplantation. The clinical expression of the recurrence of the hepatic disease is modulated by the immunosuppression...

Splenic artery steal syndrome after liver transplantation: an alternative technique of embolization.

Arterial steal syndrome after orthotopic liver transplantation (OLT) is characterized by arterial hypoperfusion of the graft, which is caused by a shift in blood flow into the splenic or gastroduodenal arteries. It causes hepatic hypoperfusion with attendant clinical manifestations of elevated liver function enzymes, allograft dysfunction, and cholestasis. Left untreated, the condition has a significant potential risk for postoperative morbidity and graft loss. Herein we have reported the case of a 68-year-old woman who developed splenic artery steal syndrome (SASS) after deceased donor liver transplantation. She was diagnosed by duplex Doppler ultrasonography and celiac trunk angiography, and subsequently treated with splenic artery embolization.

Selección del receptor para trasplante hepático / Recipient selection for liver transplantation

In the last few years, there have been developments In many aspects of liver transplantation. Improvements in surgical techniques and immunosuppression markedly increased the success rates of liver transplantation. This success has lead to increasing numbers of recipients. However, the availability of cadaveric organs for transplantation has not been changed in the last 10 years, resulting in a growing discrepancy between donors and recipients. Thus, it is necessary to properly select the best candidates for a successful liver transplant. This article will review the indications and contraindications for liver transplantation in the Model for End Stage Liver Disease (MELD) score era.

En los últimos años han existido avances importantes en el trasplante hepático. La evolución en la cirugía hepática y la aparición de mejores inmunosupresores han incrementado de manera importante el éxito en el trasplante hepático. Este éxito ha aumentado el número de receptores; sin embargo, al mismo tiempo el número de órganos ha permanecido estable en los últimos 10 años, teniendo como resultado un incremento en la disparidad entre donadores y receptores. Por lo tanto es necesario conocer quiénes son los mejores candidatos para un trasplante hepático. En este artículo se revisarán las indicaciones y contraindicaciones en el trasplante hepático en la era de la clasificación de MELD (por sus siglas en inglés Model for End Stage Liver Disease).

[Recipient selection for liver transplantation]. / Selección del receptor para trasplante hepático.

In the last few years, there have been developments in many aspects of liver transplantation. Improvements in surgical techniques and immunosuppression markedly increased the success rates of liver transplantation. This success has lead to increasing numbers of recipients. However, the availability of cadaveric organs for transplantation has not been changed in the last 10 years, resulting in a growing discrepancy between donors and recipients. Thus, it is necessary to properly select the best candidates for a successful liver transplant. This article will review the indications and contraindications for liver transplantation in the Model for End Stage Liver Disease (MELD) score era.