Liver transplantation for erythropoietic protoporphyria with hepatic failure: a case report

Erythropoietic protoporphyria (EPP) is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excessive production and biliary excretion of protoporphyrin. The main clinical features--photosensitivity and hepatobiliary disease that may progress to liver failure--are caused by the toxicity of protoporphyrin. Orthotopic liver transplantation is an effective treatment of liver failure caused by EPP. In this report we have described an EPP Chinese man with end-stage liver disease. He was successfully transplanted. A 3-year follow-up study of protoporphyrin levels, liver tests, and liver biopsies showed no EPP recurrence after liver transplantation.     

大鼠原位辅助性肝移植治疗急性肝功能衰竭

为了评价大鼠原位辅助性部分肝移植（ＡＰＯＬＴ）对急性肝功能衰竭的支持作用。切除７５％的肝脏并阻残余肝脏的血供５０分钟导大鼠急性肝功能衰竭。治疗组受体计切除７５％并将３０％的供肝植于原位，然后阻断残余的右上叶的右下叶之血供５０分钟。结果显示，大鼠急性肝功能衰竭的５天生存率仅３３％，而接受ＡＰＯＬＴ者５天生存率和移植肝存活率分别为８０％和７３％，术后第５天肝功能基本恢复正常。可见，大肝切除和余肝缺血诱     

Liver transplantation is possible in some patients with liver metastasis of colon cancer

Liver metastases from colorectal cancer are an absolute contraindication for liver transplantation. Aggressive therapy with liver resection and local chemotherapy in selected patients may be able to provide long-term cure. Given the risks of tumor recurrence, whether patients with post chemotherapy complications leading to liver failure should be offered transplantation is a challenging question in an era of limited organ availability. Herein we have presented 2 cases of liver transplantation performed in patients with colorectal cancer metastases treated with liver resection followed by hepatic artery infusion chemotherapy leading to development of sclerosing cholangitis and eventual liver failure. This report demonstrates that liver transplantation may be an option in selected patients with colorectal cancer liver metastases that have been well treated.     

Ectopic liver (choristoma) associated with the gallbladder encountered during laparoscopic cholecystectomy: a case report

Ectopic liver has been but rarely described usually in the vicinity of liver such as on the gallbladder, hepatic ligaments, diaphragm, thoracic cavity, adrenal glands, pancreas, omentum, spleen, esophagus and umbilical cord. A simple classification for anomalous liver tissues found on the wall of gallbladder is 1. Accessory liver lobe 2. Ectopic nodule 3. Aberrant microscopic tissue. Ectopic nodules of liver tissue attached to the gallbladder are completely detached from the liver and has been described by various names such as accessory lobe, ectopic liver, accessory liver and heterotopic liver but the specific pathological term for this entity is choristoma introduced by Albert in 1904 meaning displacement. Several possible mechanisms may explain ectopic liver at various sites such as the development of an accessory lobe of the liver with atrophy or regression of the original connection to the main liver or migration of pars hepatica to the rudiment of various organs. In this paper we present a case of ectopic liver or choristoma attached to the gallbladder encountered during an elective laparoscopic cholecystectomy which was successfully removed with the gallbladder.     

Autoimmune Hepatitis in an Immunosuppression-Free Patient Who Underwent Living Donor Liver Transplantation From an Identical Twin: A Case Report

Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease.     

Surgical prospects for liver metastases

The recent advances in liver surgery have made it possible to perform liver resections in an increasing number of patients with consequent improvement in the results. This coincides with an amplification of the indications to liver surgery for metastases. Besides the development of radiological procedures as applied to liver surgery and more effective chemotherapy protocols, the actual approach to patients with liver metastases is shared by three figures - the surgeon, the radiologist and the oncologist. Currently it has been shown that liver resections for metastases are possible with a meaningful increase of survival in the case of colorectal and neuroendocrine liver metastases and in selected cases of non-colorectal non-neuroendocrine metastases. From the technical point of view the most remarkable aspect is the possibility of expanding the criteria of resectability by means of liver resections in one or two steps associated with portal vein embolisation or ligation of a portal branch. It is also possible to perform iterative liver resections and liver transplantation in selected cases of neuroendocrine liver metastases.     

Complete hepatic ischemia due to torsion of a large accessory liver lobe: first case to require transplantation

Anatomical abnormalities of the liver are extremely rare. Although the majority of cases with an accessory liver are not detected, it can give rise to various clinical symptoms like recurrent abdominal pain and impaired liver function. Here we present the first case of orthotopic liver transplantation in a patient with hepatic ischemia caused by complete vascular occlusion due to a twisted accessory liver lobe. Although rare, an accessory liver lobe may cause serious and life-threatening problems and should therefore be kept in mind in patients presenting with acute abdominal pain.     

Isolated hepatocytes and their potential therapeutic use

Isolated hepatocytes in culture represent an idoneous system for the study of liver physiology and metabolism. Furthermore, they are also widely utilized in pharmacological and toxicological study, in evaluating xenobiotic substance effects on the liver. In this paper, we reviewed the enzymatic methods for liver cell isolation in some mammalian species, as well as the techniques for qualitative and quantitative evaluation of cell number, vitality, purity, morphology and function. Recently, there has been a renewed interest in hepatocyte transplantation and hepatocyte-based liver support systems. From a clinical point of view, isolated hepatocytes could be useful in temporarily substituting an acutely damaged liver, a liver affected by a chronic pathology, or to correct an inherited liver disease carrying a severe metabolic derangement. Early experimental results of allogeneic hepatocyte transplantation, as well as the first clinical trials of bioartificial liver support systems employing xenogeneic hepatocytes are promising and contribute to maintain that interest in liver cell isolation and purification methods.     

肝损伤过程中eNOS和IL-10的基因表达对肝再生调控机制的探讨

目的探讨内皮型一氧化氮合酶（ｅＮＯＳ）和白细胞介素１０（ＩＬ１０）在肝再生信息传导中的作用。方法切除７０％肝脏,制备肝再生模型,注射５０％ＣＣｌ４和脾切除引起肝损伤和机体免疫功能低下,４８小时后采用逆转录ＰＣＲ和点杂交方法检测ｅＮＯＳ和ＩＬ１０ｍＲＮＡ基因表达,免疫组化ＬＳＡＢ法检测ＩＬ１０蛋白在肝内的分布,流式细胞仪（ＦＣＭ）检测再生肝ＤＮＡ含量,采用统计学方法进行再生肝组织ＤＮＡ含量与ＩＬ１０和ｅＮＯＳ变化的相关分析,以此判断ＩＬ１０和ｅＮＯＳ的变化对肝再生的影响。结果ｅＮＯＳ的表达同肝细胞的再生呈正相关,而ＩＬ１０的表达与其呈负相关。结论ｅＮＯＳ和ＩＬ１０对肝再生具有明显的调控作用,无论在生理或在病理状态下都是如此,并且二者呈现一种完全相反的调控方式,同时受到脾脏或全身免疫系统的影响     

Changes after major resection of experimental cirrhotic liver

In an investigation of resectability and changes in the remnant liver after major resection of the cirrhotic liver, liver cirrhosis was induced experimentally in dogs—hemodynamically, by constriction of the hepatic vein and pharmacologically, by the administration of DMNA—after which approximately 45 per cent of the liver was resected.     

Ectopic umbilical liver in conjunction with biliary atresia: uncommon association

The case of a neonate with an ectopic liver in the umbilicus in conjunction with biliary atresia in the liver proper and an ectopic pancreas in the jejunum is reported. Following excision of the ectopic umbilical liver and Kasai type 1 hepatic portoenterostomy, bile fistula originating in the anterior inferior area of the right lobe of the liver was a complication, and it was successfully treated by construction of hepaticojejunostomy. No similar case has been reported in English language literature. It is of particular interest that the pathological features of the ectopic liver and the liver proper are quite similar.     

Postprandial hepatic glycogen synthesis in liver transplant recipients

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.     

Auxiliary partial orthotopic liver transplantation in acute liver failure due to hepatitis B

Auxiliary partial orthotopic liver transplantation is an alternative therapeutic modality in acute liver failure, wherein the capacity of native liver to regenerate is preserved. A case of acute liver failure due to hepatitis B in an 18-year-old male patient treated with an auxiliary left lateral segment graft is described. There was no recurrence of hepatitis B in the auxiliary graft and the patient cleared the virus after 9 months whilst receiving lamivudine. Immunosuppression was withdrawn at 14 months, and the auxiliary graft atrophied secondary to hepatic arterial conduit thrombosis, possibly precipitated by immunosuppression withdrawal. The native liver regenerated completely, and the patient is well and off immunosuppressive and antiviral therapy 3 years after transplantation. Auxiliary partial orthotopic liver transplantation is an attractive treatment option in acute liver failure due to hepatitis B infection and allows a life free of long-term immunosuppression.     

Transplantation of a severely lacerated liver – a case report with review of the literature

Abstract:  Using lacerated livers for liver transplantation (LTx) can add an option to the extended donor criteria. We present an LTx case using a severely lacerated liver and review of the literature for reported cases. We used a high-grade lacerated liver from a 19-yr-old brain-dead patient caused by traffic accident. The liver had grade IV and II lacerations in the right and left lobe, respectively. Lacerations were managed by sealants, stitching and perihepatic packing. The liver was transplanted to a 49-yr-old man suffering from hepatocellular carcinoma on hepatitis C-induced liver cirrhosis. The two-yr follow-up was uneventful. All published LTx cases using traumatized livers (n = 18) were analyzed. The liver injury ranged from subcapsular hematoma to deep ruptures. Most reported lacerations were in the right lobe, which were managed by digital compression, suturing, electrocautery, and perihepatic packing. The reported complications were primary non- (18%), or poor function, liver abscess, bilioma, and subhepatic hematoma each in one case (5.5%). Six-month graft and patient survival were 71% and 88%, respectively. With meticulous management lacerated livers can be transplanted successfully. Because of complexity of the management, procurement and transplantation should be done by experienced liver surgeons. These organs are marginal grafts and should be offered to selected patients.     

Hepatocyte transplantation for total liver repopulation

Hepatocyte transplantation (HT) is an attractive therapeutic alternative to liver transplantation. A number of experiments have shown the feasibility of total liver parenchymal cell replacement by transplanted hepatocytes. In this review, we would like to highlight researches and clinical reports of HT for liver repopulation. Cellular source of clinical HT should be safety. Immortalized cells, hepatic stem cells, and other stem cells have been used for an experimental model for HT. The exact mechanism of the cell engraftment after HT has not been completely understood, although there were some markers to detect and investigate transplanted cells. In order to achieve liver repopulation following HT, a mild hepatic damage may need to facilitate cell engraftment and replace the host liver by transplanted cells. Hormonal factor may use for the same purpose. Despite the results of preclinical studies promising clinical benefits for cell therapy, the clinical experience of HT has been disappointing, except in a few cases. HT may become an alternative for liver transplantation in the future; however, many efforts should made before establishing an effective method for HT and liver replacement therapy.     

Flupirtine-induced hepatic failure requiring orthotopic liver transplant

We present the case of a 48-year-old otherwise healthy man who required an urgent liver transplant owing to acute liver failure after flupirtine treatment. After 3 months of daily flupirtine intake as treatment for pseudoradicular pain syndrome, he presented at our institution with signs of jaundice and hepatic encephalopathy. Laboratory results showed elevated liver transaminases, and the liver histopathology supported the assumed drug-induced liver injury. After listing him for an urgent liver transplant, he was given a liver graft from a 21-year-old man. Despite a rejection episode on day 11 after the surgery (which was successfully treated by steroid pulse therapy), the postoperative course was uneventful and the patient recovered completely. To the best of our knowledge, this is the first report of a liver transplant for acute liver failure after taking flupirtine.     

Liver regeneration using a hybrid artificial liver support system

We have developed two types of hybrid artificial liver support system (HALSS) that use hepatocyte organoid culture: (1) a PUF-HALSS comprising an artificial liver module using polyurethane foam (PUF), in which hepatocytes form spheroids in its pores, and maintained liver-specific functions for at least ten days in vitro; (2) an LLS-HALSS that uses a liver lobule-like structure (LLS) module containing hollow fibers with a microregular arrangement in which hepatocytes in the extra-fiber space of the module form the organoids by centrifugation that maintain liver-specific functions for at least two months in vitro. In preclinical experiments, a PUF-HALSS was applied to a pig having liver failure. To evaluate the effect of liver regeneration, a PUF- and an LLS-HALSS were applied to a rat having reversible hepatic failure. Each HALSS was effective in supporting liver function, stabilization of general conditions and recovery from liver failure state. These results indicate that these HALSS may be useful to treat liver failure patients until liver transplantation or until regeneration of the native liver.     

Idiopathic extensive peliosis hepatis treated with liver transplantation

A 50-year-old Danish man, who neither had wasting disease nor was taking steroid-containing drugs, complained of abdominal distension, due to a markedly enlarged liver. Percutaneous needle biopsies were taken from the liver, and the findings gave suspicion of a neoplastic tumor. Because of reduced liver function and treatment-resistant ascites, he underwent liver transplantation without a definite preoperative diagnosis. The resected liver weighed 2900g, and almost all of the parenchyma was destroyed and replaced by multicystic blood-filled spaces, diagnosed as extensive peliosis hepatis complicating liver cirrhosis. Extensive peliosis with liver cirrhosis is a rare condition. Only two cases, caused by contraceptives and treated by liver transplantation, are reported in the English-language literature. We could find no cause other than alcohol abuse lasting several years in this patient, and classified the present case as idiopathic extensive peliosis hepatis. Although scarce subjective findings and misleading liver biopsies made an exact diagnosis difficult, an orthotopic liver transplantation was the only treatment for such complicated peliosis hepatis.     

Liver transplantation for primary and metastatic liver cancers

Liver transplantation for hepatic malignancies has emerged as a well‐documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long‐term effects of immunosuppression; however, long‐term and disease‐free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo‐ and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re‐evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long‐term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well‐designed trials.     

Direct vascular implantation of liver for hepatic regeneration after interruption of the portal vein and hepatic artery

This paper reports an experiment in which nine dogs were subjected to extended partial hepatectomy in addition to interruption of the portal vein and hepatic arterial system. The lobe of the liver which sustained the dog was supplied solely by blood from an extrahepatic vascular source previously implanted directly into the liver parenchyma. It is hoped that the ability of a small segment of liver to regenerate, under these conditions, might prove clinically useful in some patients with tumors of the liver, gallbladder, or extrabiliary system who, by present criteria, are considered inoperable.