Liver transplantation in a 7-month-old girl with Caroli's disease

Caroli's disease (including Caroli's syndrome) is a rare autosomal recessive disorder of the liver characterized by diffuse cystic dilatation of the intrahepatic bile ducts. The disease may present at any age and is characterized by recurrent episodes of biliary obstruction, cholangitis, hepaticolithiasis, and liver abscesses. Caroli's syndrome is further associated with congenital hepatic fibrosis and portal hypertension. Patients with recurrent complications or cirrhosis may die because of recurrent infection, portal hypertension, liver failure, or cholangiocarcinoma. Liver transplantation is the treatment of choice for these complicated patients. Here we describe the youngest reported patient with Caroli's syndrome treated successfully using liver transplantation and review the recent literature.     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation represents an important treatment option for patients with intestinal failure. Early attempts were hindered by technical and immunological complications. However, significant developments in immunosuppressive therapy have led to marked improvements in outcomes in recent years. The main indications for intestinal transplantation are life-threatening complications or unacceptable quality of life on total parenteral nutrition (TPN), or following evisceration for extensive intra-abdominal tumours. In suitable patients, in the absence of significant liver disease, an isolated intestinal graft is appropriate. A combined liver and intestinal transplant is indicated in patients with significant liver disease, almost always as a result of long-term TPN. Pathology affecting the foregut may require more extensive grafts, including the stomach, duodenum and pancreas. Multivisceral transplantation is technically demanding. The transplant recipient has frequently undergone multiple previous laparotomies and may present with multiple stomata, fistulae, collections, distortion of intra-abdominal anatomy and significant contraction of the abdominal cavity. The most important early complications are acute rejection and sepsis, which frequently occur together. In the long term, chronic rejection and malignancy are the leading causes of graft loss and mortality and immunosuppression related renal impairment a major source of morbidity. It is hoped that ongoing improvements in intestinal and multivisceral transplantation may eventually justify its use as a primary alternative to long-term TPN.     

A single centre experience of liver disease in adults with cystic fibrosis 1995-2006.

BACKGROUND: Liver disease is an important cause of death in adults with cystic fibrosis (CF). Ursodeoxycholic acid (UDCA) may slow progression. Managing varices and timely evaluation for liver transplantation are important. METHODS: Adults with CF underwent annual review. Abnormalities of liver function tests or ultrasound prompted referral to the CF/liver clinic where UDCA was commenced. Endoscopic surveillance for varices was undertaken if ultrasound suggested portal hypertension. RESULTS: 154 patients were followed for a median 5 years. 43 had significant liver disease, 29 had cirrhosis with portal hypertension and 14 had ultrasound evidence of cirrhosis without portal hypertension. All started UDCA. Only one patient developed chronic liver failure and none required liver transplantation. 27 underwent endoscopy; 1 required variceal banding, the others had insignificant varices. Ultrasound was normal in 97 patients while five had steatosis; nine further patients had splenomegaly but no other evidence of portal hypertension. Neither spleen size nor platelet count correlated with portal hypertension. CONCLUSIONS: Liver disease was common in adults with CF but disease progression was rare. Thus liver disease detected and closely monitored in adults appeared to have a milder course than childhood CF. Splenomegaly, unrelated to portal hypertension may be a consequence of CF.     

Distal splenorenal shunts for the treatment of severe thrombocytopenia from portal hypertension in children

Profound thrombocytopenia resulting from portal hypertension may exacerbate gastrointestinal bleeding, precipitate spontaneous bleeding, preclude surgical intervention for associated disorders, and severely limit life-style because of the danger of splenic injury. Although splenectomy can reverse the thrombocytopenia, the procedure should be avoided in children. We reviewed our experience with distal splenorenal shunting (DSRS) in children, particularly when performed for the sole purpose of reversing severe thrombocytopenia resulting from portal hypertension. DSRS was performed in 11 children between the ages of 7 and 15 years: five for severe thrombocytopenia (group 1), four for advanced hypersplenism and congenital hepatic fibrosis prior to renal transplantation (group 2), and two for esophageal bleeding (group 3). One child in group 1 with severe heart disease and Child’s class C cirrhosis due to hepatitis C died of progressive cardiac failure and was excluded from further analysis. Of the eight remaining patients in groups 1 and 2, four children had congenital hepatic fibrosis, two had portal vein thrombosis, one had hepatitis B, and one had Wilson’s disease. After DSRS, the mean platelet count increased from 37,000 ±18,000 to 137,600 ±81,000 (P = 0.01). The platelet count improved significantly in all seven children with presinusoidal portal hypertension or stable cirrhosis but did not increase in the child with hepatitis Band Child’s class B cirrhosis. The white blood cell count increased from an average of 3.3 ±1.1 to 5.4 ± 2.6 (P= 0.02). There were no postoperative complications in this group. The improved platelet count allowed the four children with congenital hepatic fibrosis and renal failure to undergo renal transplantation with full posttransplant immunosuppression including azathioprine. Postoperative Doppler ultrasound examination demonstrated shunt patency at 6 months in all cases. Spleen size decreased appreciably in all children in groups 1 and 2. All children were able to resume full activity including contact sports. In summary, DSRS effectively controls profound thrombocytopenia resulting from presinusoidal portal hypertension or stable cirrhosis without sacrificing the spleen and should be the treatment of choice for this condition. Presented at the British Association of Pediatric Surgeons Annual International Congress, Istanbul, Turkey, July 22–25, 1997.     

特发性门静脉高压症的诊治现状

特发性门静脉高压症(IPH)非常罕见,其特点是有门静脉高压,但没有肝硬化,有门静脉小分支堵塞或狭窄,却没有肝静脉和门静脉主干的堵塞。该疾病尚有其它命名,如:特发性非硬化性门静脉高压症、非肝硬化性门静脉纤维化等。IPH病因及发病机制未明确,可能与遗传、免疫、感染等因素相关。临床表现上IPH以脾功能亢进、胃食管静脉曲张为主,而少有肝功能不全、肝性脑病。诊疗上尚有不少争议,目前IPH的诊断为排除性诊断,治疗上多参考肝硬化性门静脉高压的指南。IPH预后资料不多,目前认为较肝硬化性门静脉高压者预后更佳,只有少数患者进展至肝衰竭。     

Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by mucocutaneous and visceral telangiectasia. Hepatic involvement with vascular malformations may lead to portal hypertension, biliary ischemia, and high-output cardiac failure. Liver transplantation is indicated for life-threatening disease but carries significant risk from surgery and chronic immunosuppression. We report a case of a 47-year-old woman with HHT successfully treated with the vascular endothelial growth factor (VEGF) antibody bevacizumab. The patient was referred for consideration of liver transplantation because of hepatic HHT leading to high-output cardiac failure, diuretic resistant ascites, cholestasis, and malnutrition. As she was considered a high-risk candidate for transplantation, she underwent 6 courses of bevacizumab (5 mg/kg) over 12 weeks. A dramatic improvement in her clinical state was observed after 3 months with reversal of cholestasis, resolution of cardiac failure and ascites, and improvement in nutritional status with a 10% dry weight increase. Treatment induced a marked reduction in liver vascularity and halving of her liver volume from 4807 to 2269 mL over 6 months. This was associated with normalization of her cardiac output from 10.2 to 5.1 L/minute. Correspondingly, she ceased diuretic medications, returned to full-time work, and was delisted as a transplant candidate. She remains well 6 months after completing treatment. In conclusion, antagonism of VEGF receptors led to a dramatic regression of hepatic vascular malformations and reversal of high-output cardiac failure and complications of portal hypertension in this patient with HHT. Bevacizumab may potentially alleviate the need for liver transplantation in this group of patients.     

Severe venoocclusive disease after liver transplantation treated with transjugular intrahepatic portosystemic shunt

Venoocclusive disease (VOD) is due to hepatic sinusoidal lining injury leading to portal hypertension; its incidence after liver transplantation is about 2%. When severe, it does not respond to medical therapy and has a high mortality; retransplantation is the only therapeutic option. However, there are no detailed data regarding the use of transjugular intrahepatic portosystemic shunt for VOD after liver transplantation. We describe two patients who developed severe VOD after liver transplantation, failed defibrotide therapy, and were treated by transjugular intrahepatic portosystemic shunt (TIPS). The portal hypertension resolved completely and one had full histological recovery. We believe that TIPS should be attempted as it may resolve progressive portal hypertension and the hepatic congestion, while allowing the clinician time for listing for further liver transplantation if the patient fails to respond.     

Recovery from liver dysfunction after adult isolated intestinal transplantation without liver grafting

PURPOSE: We sought to evaluate liver function recovery after isolated intestinal transplantation in adults with irreversible intestinal failure. PATIENTS AND METHODS: Over a 5-year period, we transplanted 34 adult patients, 25 of whom received an isolated intestinal graft, 4 a multivisceral graft without a liver, and 5, a multivisceral graft with a liver. Among the group of patients transplanted with the isolated graft we selected 14 recipients with pretransplant liver dysfunction, namely, a serum bilirubin >2 mg/dL (normal value: 1.2) and/or transaminases >100 IU/mL (NV, 37/40). Other inclusion criteria were total parenteral nutrition, period > 3 months, no diagnosis of portal hypertension or cirrhosis. Two patients had biopsy-proven liver fibrosis. RESULTS: At discharge, all patients recovered liver function to normal values: mean bilirubin blood level was 0.9 +/- 0.96 mg/dL (range: 0.3-1.6) and mean transaminases were 26 +/- 9 and 31 +/- 18 IU/mL (range: 10-44/27-65). After a mean follow-up of 2 years, only one patient has an elevated alanine aminotransferase level without clinical signs of liver disease. Type of pretransplant liver disease did not impact on survival rates. CONCLUSION: In selected cases, an isolated intestinal or a multivisceral graft without a liver can represent a "liver salvage therapy" for an early failing liver in patients with irreversible intestinal failure. Pretransplant liver disease is not a negative prognostic factor.     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation represents an important treatment option for patients with intestinal failure. Early attempts were hindered by technical and immunological complications. However, significant developments in immunosuppressive therapy have led to marked improvements in outcomes in recent years. The main indications for intestinal transplantation are life-threatening complications or unacceptable quality of life on total parenteral nutrition (TPN), or following evisceration for extensive intra-abdominal tumours. In suitable patients, in the absence of significant liver disease, an isolated intestinal graft is appropriate. A combined liver and intestinal transplant is indicated in patients with significant liver disease, almost always as a result of long-term TPN. Pathology affecting the foregut may require more extensive grafts including the stomach, duodenum and pancreas. Multivisceral transplantation is technically demanding. The transplant recipient has frequently undergone multiple previous laparotomies and may present with multiple stomata, fistulae, collections, distortion of intra-abdominal anatomy and significant contraction of the abdominal cavity. The most important early complications are acute rejection and sepsis, which frequently occur together. In the long-term, chronic rejection and malignancy are the leading causes of graft loss and mortality. It is hoped that ongoing improvements in intestinal and multivisceral transplantation may eventually justify its use as a primary alternative to long-term TPN.     

门静脉动脉化在肝胆外科中的应用现状与展望

自首次将门静脉动脉化(PVA)用于门静脉高压症患者治疗以来,PVA的概念一直受到关注.在某种特殊形式下,PVA技术在肝胆外科中仍有一定的应用价值.然而,PVA毕竟改变了正常的人体生理解剖关系,对于它在肝胆外科中应用也存在较多争议.文中综述门静脉动脉化在肝动脉切除和(或)损伤、急性肝功能衰竭以及肝移植中的应用现状,并对以后的研究进行初步的展望.

Abstract：

Since portal vein arterialization(PVA) was firstly introduced as a treatment in patients with portal hypertension due to liver cirrhosis, the concept of PVA has drawn much attention. In special situations, in hepatobiliary surgery, this procedure remains useful. However, PVA is unphysiological and there is much controversy on its use.This article reviews the current status of PVA in hepatic artery resection or injury, in acute liver failure and in liver transplantation, and suggests future directions in research in PVA.     

Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children

Liver dysfunction is a well-recognized complication of intestinal failure in children. Advances in total parenteral nutrition (TPN) have allowed these children to survive while their intestinal tract gradually adapts. Unfortunately TPN may lead to cholestatic liver disease particularly in the young children. Progression of liver disease is associated with a poor prognosis and is an indication for small bowel transplantation.We report our experience of orthotopic liver transplantation in four children with short gut and sequential liver and small bowel transplantation in one child. All children had TPN-related liver failure. Causes of intestinal failure included necrotising enterocolitis (n=2), gastroschisis (n=1), intestinal atresia (n=1), and megacystic, microcolon syndrome (n=1). At the time of liver transplantation the children's mean age was 10.9 months (2.5-24) and weight 6.7 kg (4.8-10.1). The mean serum bilirubin was 522 micromol/liter (299-823), aspartate transaminase 423 IU/liter (49-1024) and international normalized ratio 2.8 (2-3.9). There were two deaths both from respiratory failure secondary to adenovirus pneumonia including the child who received a sequential small bowel transplant. Three children with isolated liver grafts are alive and off TPN at 20 months (mean) follow up (range 6-35). Isolated orthotopic liver transplantation has a role in selected children with intestinal failure, particularly those with short but normally functioning gut and progressing with satisfactory intestinal adaptation but developing liver disease. Those children with TPN-related liver disease and unadapted gut or irreversible intestinal disease need combined liver and small bowel transplantation. Sequential small bowel transplantation is feasible after orthotopic liver transplantation and may provide an option for the child with terminal liver and small bowel failure.     

Liver failure after major hepatic resection

Introduction  The consequence of excessive liver resection is the inexorable development of progressive liver failure characterised by the typical stigmata associated with this condition, including worsening coagulopathy, hyperbilirubinaemia and encephalopathy. The focus of this review will be to investigate factors contributing to hepatocyte loss and impaired regeneration. Methods  A literature search was undertaken of Pubmed and related search engines, examining for articles relating to hepatic failure following major hepatectomy. Results  In spite of improvements in adjuvant chemotherapy and increasing surgical confidence and expertise, the parameters determining how much liver can be resected have remained largely unchanged. A number of preoperative, intraoperative and post-operative factors all contribute to the likelihood of liver failure after surgery. Conclusions  Given the magnitude of the surgery, mortality and morbidity rates are extremely good. Careful patient selection and preservation of an obligate volume of remnant liver is essential. Modifiable causes of hepatic failure include avoidance of sepsis, drainage of cholestasis with restoration of enteric bile salts and judicious use of portal triad inflow occlusion intra-operatively. Avoidance of post-operative sepsis is most likely to be achieved by patient selection, meticulous intra-operative technique and post-operative care. Modulation of portal vein pressures post-operatively may further help reduce the risk of liver failure.     

门静脉动脉化在肝胆外科中的应用现状与展望

自首次将门静脉动脉化(PVA)用于门静脉高压症患者治疗以来,PVA的概念一直受到关注.在某种特殊形式下,PVA技术在肝胆外科中仍有一定的应用价值.然而,PVA毕竟改变了正常的人体生理解剖关系,对于它在肝胆外科中应用也存在较多争议.文中综述门静脉动脉化在肝动脉切除和(或)损伤、急性肝功能衰竭以及肝移植中的应用现状,并对以后的研究进行初步的展望.     

Intestinal and multivisceral transplantation

Intestinal and multivisceral transplantation represents an important treatment option for patients with intestinal failure. Early attempts were hindered by technical and immunological complications. However, significant developments in immunosuppressive therapy have led to marked improvements in outcomes in recent years. The main indications for intestinal transplantation are life-threatening complications or unacceptable quality of life on total parenteral nutrition (TPN), or following evisceration for extensive intra-abdominal tumours. In suitable patients, in the absence of significant liver disease, an isolated intestinal graft is appropriate. A combined liver and intestinal transplant is indicated in patients with significant liver disease, almost always as a result of long-term TPN. Pathology affecting the foregut may require more extensive grafts including the stomach, duodenum and pancreas. Multivisceral transplantation is technically demanding. The transplant recipient has frequently undergone multiple previous laparotomies and may present with multiple stomata, fistulae, collections, distortion of intra-abdominal anatomy and significant contraction of the abdominal cavity. The most important early complications are acute rejection and sepsis, which frequently occur together. In the long-term, chronic rejection and malignancy are the leading causes of graft loss and mortality and immunosuppression related renal impairment a major source of morbidity. It is hoped that ongoing improvements in intestinal and multivisceral transplantation may eventually justify its use as a primary alternative to long-term TPN.     

Preoperative transjugular intrahepatic portosystemic shunt (TIPS) for cirrhotic patients undergoing abdominal and pelvic surgeries

Background  Surgery for patients with cirrhosis is associated with increased morbidity and mortality. Perioperative complications including hemorrhage, wound dehiscence, and peritonitis result from underlying portal hypertension. Perioperative control of portal hypertension could decrease the risk of such complications. This study aimed to describe the authors’ experience with the placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with cirrhosis to improve surgical outcomes. Methods  A retrospective chart review was performed for seven patients who underwent TIPS placement before elective abdominal or pelvic surgery at the University of Colorado Health Sciences Center from 1998 to 2006. The TIPS indication for each patient was to minimize perioperative complications. Results  The seven patients in this study underwent their planned surgical procedure within a mean of 13 days from the time of TIPS placement. Two patients required a blood transfusion of two units or less. Three patients experienced a total of four postoperative complications including wound infection, peritonitis, pneumonia, and new ascites. One patient died of liver failure 14 months after surgery. Conclusions  The preparation of patients with cirrhosis and portal hypertension for elective surgery using preoperative portal decompression may decrease the risk of perioperative morbidity and mortality.     

Portosystemic shunts in children: a 15-year experience

BACKGROUND: The role of portosystemic shunt (PSS) in children with portal hypertension has changed because of acceptance of liver transplantation and endoscopic hemostasis. We report our experience with PSS, mainly the distal splenorenal shunt, to define its role in the management of variceal bleeding. STUDY DESIGN: From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed. RESULTS: There were 14 boys and 6 girls; mean age was 11 years (range 3 to 18 years). Seventeen distal splenorenal and three mesocaval venous interposition shunts were performed. There was no operative mortality, 19 patients were alive at a median followup of 31 months (range 4 to 168 months) without evidence of recurrent gastrointestinal bleeding. One patient underwent transplantation 2 years after PSS and 1 patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), biliary atresia (n = 3), congenital hepatic fibrosis (n = 2), hepatitis C cirrhosis (n = 1), and Budd-Chiari syndrome (n = 1). Eighteen children were Child-Turcotte-Pugh class A and the remaining two were class B. One patient had two episodes of hematemesis after PSS. Two patients had worsening ascites. One patient had mild encephalopathy and one patient had shunt stenosis requiring angioplasty. CONCLUSIONS: PSS is a safe and durable therapy for pediatric patients with portal hypertension. Liver transplantation should be reserved for children with poor synthetic function associated with variceal bleeding. PSS may also serve as a bridge to transplantation in patients with preserved hepatic function. PSS, in particular the distal splenorenal shunt, has produced excellent results. This experience challenges the need for alternative forms of portal decompression.     

Natural history of unexplained chronic hepatitis after liver transplantation.

Unexplained chronic hepatitis (CH) in the adult liver allograft recipient is not uncommon, but its natural history and clinical significance is unknown. A retrospective study was undertaken of adult liver allograft recipients to determine the frequency and natural history of unexplained CH. We evaluated only those patients who had undergone >or=2 liver biopsies after 6 months and were grafted for indications where recurrent disease could be confidently excluded (alcoholic liver disease [ALD] in those who remained abstinent and fulminant hepatic failure [FHF] from drug reactions). Of 288 patients who were transplanted for ALD or FHF, 30 fulfilled the above criteria. CH was first diagnosed at a median of 15.25 months after transplantation. A total of 24 patients showed mild necroinflammatory changes, and 12 had mild or moderate fibrosis. Liver tests did not reflect the presence or degree of inflammation or fibrosis. After a median of 4 years, necroinflammatory scores were increased in 5; new or progressive fibrosis was noted in 13%; 3 had developed cirrhosis; and 5 developed clinical evidence of portal hypertension. Progressive fibrosis was associated with a high titer of anti-nuclear antibodies (>1:1600) and a portal tract plasma cell infiltrate. There was a trend for correlation between necroinflammatory activity and fibrosis stage, but this did not reach statistical significance (P = 0.06). Serum alkaline phosphatase (P = 0.012) and female gender of the donor (P = 0.033) were associated with progressive fibrosis. Unexplained CH is not uncommon in the liver allograft and may progress to established cirrhosis in a subgroup of patients transplanted for ALD or FHF. Standard liver tests do not reflect the extent of these changes, so protocol liver biopsies may be required to detect these changes. We recommend careful history and follow-up in these patients.     

Combined liver‐kidney transplantation for children with autosomal recessive polycystic kidney disease (ARPKD): indication and outcome

In ARPKD, mutations in the PKHD1 gene lead to remodeling of the kidneys and liver. These may result in progressive liver fibrosis with portal hypertension requiring combined liver and kidney transplantation (CLKT). There is currently no consensus on the indication for CLKT and data on long‐term outcomes are scarce. We analyzed in detail the pretransplant liver symptomatology, laboratory and ultrasound data, histological studies, and genotypes in eight patients undergoing CLKT. The median age was 10.1 years (range 1.7–16) and median follow‐up was 4.6 years (range 1.1–8.9). All patients had clinical signs of portal hypertension and abnormal ultrasound findings. Congenital hepatic fibrosis was present in all pretransplant biopsies (6 out of 8 patients) and in all explanted livers. All patients survived; liver and kidney graft survival was 72% and 88%, respectively. Liver and kidney function were stable in all patients with a median eGFR of 70 ml/min/1.73 m² (range 45–108 ml/min/1.73 m²). Height‐SDS improved significantly after 12, 24, and 36 months (P = 0.016, 0.022 and 0.018 respectively). The indication for CLKT remains challenging and controversial. A favorable outcome for patients with ARPKD can be achieved by using the degree of portal hypertension, longitudinal ultrasound examinations, and preoperative liver histology as parameters for CLKT.     

Radiofrequency ablation for hypersplenism in patients with liver cirrhosis: A pilot study

Radiofrequency ablation is a relatively new technique used for local ablation of unresectable tumors. We investigated the feasibility and eficacy of radiofrequency ablation for hypersplenism and its effect on liver function in patients with liver cirrhosis and portal hypertension. Nine consecutive patients with hypersplenism due to cirrhotic portal hypertension underwent radiofrequency ablation in enlarged spleens. The ablation was performed either intraoperatively or percutaneously. Patients are followed up for over 12 months. After treatment, between 20% and 43% of spleen volume was ablated, and spleen volume increased by 4%–10.2%. White blood cell count, platelet count, liver function, and hepatic artery blood flow showed significant improvement after 1-year follow-up. Splenic vein and portal vein blood flow were significantly reduced. Only minor complications including hydrothorax (three of nine patients) and mild abdominal pain (four of nine patients) were observed. No mortality or other morbidity occurred. Radiofrequency ablation is a safe, effective, and minimally invasive approach for the management of splenomegaly and hypersplenism in patients with liver cirrhosis and portal hypertension. Increased hepatic artery blood flow may be responsible for sustained improvement of liver condition. Radiofrequency ablation may be used as a bridging therapy for cirrhotic patients waiting for liver transplantation.     

Liver cirrhosis and hepatic stellate cells

The cirrhosis represents the final stage of several chronic hepatic diseases and it is characterized by the presence of fibrosis and morphologic conversion from the normal hepatic architecture into structurally abnormal nodules. In the evolution of the disease there is loss of the normal vascular relationship and portal hypertension. There are also regenerative hepatocellular alterations that become more prominent with the progression of the disease. The liver transplantation continues to be the only therapeutic option in cases of disease in terminal phase. The hepatic stellate cells (HSC) are perisinusoidal cells that store vitamin A and produce growth factors, citocins, prostaglandins and other bioactive substances. They can suffer an activation process that convert them to cells with a phenotype similar to myofibroblasts. When activated, they present increased capacity of proliferation, mobility, contractility and synthesis of collagen and other components of extracellular matrix. They possess cytoplasmic processes adhered to sinusoids and can affect the sinusoidal blood flow. HSC are important in pathogenesis of fibrosis and portal hypertension.