Long-term results of liver transplantation for Wilson's disease.

UNLABELLED: Wilson's disease is a hereditary defect in hepatic copper metabolism, causing hepatic, neurological and/or psychiatric manifestations. For patients with severe disease, liver transplantation is the treatment of choice. The aim of this study was to report the long-term outcome of patients who underwent liver transplantation for Wilson's disease. PATIENTS AND METHODS: Thirteen patients with Wilson's disease, transplanted in Lyon France between January 1987 and May 2006, were including in this study: eight women and five men, aged eight to 53 years (median 20 years, seven children and six adults). The diagnosis of Wilson's disease was established before liver transplantation. RESULTS: The indication for liver transplantation was chronic (69%) or fulminant liver failure (31%). The median follow-up after liver transplantation was 10 years with 100% patient survival. Copper metabolism returned to normal in all patients. None of the patients with exclusive liver disease required chelation treatment after liver transplantation and none developed neurological symptoms of Wilson's disease. CONCLUSION: Liver transplantation totally reverses the abnormalities of copper metabolism and subsequent hepatic failure, but the course of neurological symptoms remains unpredictable. Long-term patient survival can be excellent without occurrence of neurological complications.

Rejection under alpha interferon therapy in liver transplant recipients.

Interferon alpha (IFN) is the corner stone drug for the treatment of recurrent hepatitis C (HCV) in liver transplant (LT) recipients. One of its serious potential adverse effects is acute and chronic rejection. The aim of this study was to review our experience using IFN-based therapy, in order to examine the incidence and the risk factors for rejection, and the outcome of patients who developed rejection. Between September 1990 and December 2004, 70 LT recipients were treated. Patients started antiviral treatment 16 (1-137) months after LT. Histological follow-up was available in all patients according to protocol biopsies. Rejection was diagnosed and graded according to Banff classification. Twenty-one percent of patients developed acute rejection (5 mild, 9 moderate and 1 severe) during IFN-based therapy. Patients were treated for 8 (1-15) months prior to rejection. Previous history of acute rejection before IFN therapy and treatment with pegylated-IFN was significantly associated with rejection (p = 0.04 and p = 0.02, respectively). The rejection was successfully treated in 87% of patients. No chronic rejection or graft losses were observed. Acute rejection under IFN-based therapy often occurs in LT recipients, but early diagnosis with protocol biopsies and early treatment can lead to a favorable outcome.

Unresectable hepatocellular carcinoma: survival and prognostic factors after lipiodol chemoembolisation in 89 patients.

BACKGROUND: The majority of patients with hepatocellular carcinoma are not eligible for surgical radical treatment (resection or liver transplantation) and lipiodol chemoembolisation is an efficient alternative procedure in this indication. AIMS: To identify prognostic factors in patients treated with lipiodol chemoembolisation. PATIENTS AND METHODS: During 10 years, 89 consecutive patients with unresectable hepatocellular carcinoma underwent lipiodol chemoembolisation as a single treatment. There were 80 males and 9 females, with a median age of 65 years. Treatment consisted of one to six courses of hepatic intra-arterial lipiodol with doxorubicine and gelatin sponge. RESULTS: The median survival was 13 months with a 13.6% survival rate at 4 years. Univariate analysis showed that serum levels of albumin, bilirubin, alkaline phosphatase and alpha-fetoprotein, Child's class, tumour type, tumour size and intensity of lipiodol capture after the first course of lipiodol chemoembolisation were significant prognostic factors of survival. In the multivariate analysis, four parameters remained associated with a significantly better outcome: Child's class A, largest lesion<5 cm, uninodular tumour and intense lipiodol capture. CONCLUSIONS: While lipiodol chemoembolisation is associated with good results only in some patients, in the absence of lipiodol capture, it should be ruled out.

Diagnosis and treatment of biliary obstruction caused by portal cavernoma.

While hemorrhagic complications of portal cavernoma are frequent, compression of the bile ducts by portal cavernoma is uncommon and treatment is still a matter for debate. We report here six new cases in order to describe: (a) the clinical, biological, and morphological features of this condition, and (b) the long-term results of a combined endoscopic and surgical treatment. The median age of patients at the time of diagnosis was 36.5 years. The circumstances of diagnosis were acute cholangitis (n=3), asymptomatic biological cholestasis (n=1), pruritus, jaundice and asthenia (n=1) and jaundice alone (n=1). Portal cavernoma and bile duct dilatation were confirmed by abdominal ultrasonography with pulsed color doppler and endoscopic retrograde cholangiography (ERC). Gallstones were found in four patients. Following stenting of the bile duct, there was a good outcome in two patients. In four patients, after failure of prolonged endoscopic treatment, second-line surgical portal-systemic shunting allowed removal of the biliary stent, and no recurrence of disease. In conclusion, biliary involvement in portal cavernoma is now a well-recognized entity, and our results suggest that combined endoscopic and surgical treatment could be required.

Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study.

BACKGROUNDS/AIMS: Hepatocellular carcinoma usually contains continuous capillary vessels lacking the differentiation markers specific for normal sinusoidal endothelial cells. We therefore aimed to search for alterations in endothelial cell marker expression in precancerous liver lesions. METHODS: Expression of the endothelial cell markers CD31, CD34 and BNH9 was analyzed in 138 dysplastic lesions from 40 cirrhotic patients (20 with and 20 without hepatocellular carcinoma). RESULTS: No expression of the three endothelial cell markers was detected in cirrhotic nodules and in non dysplastic regenerative macronodules. The three markers were detected in 29.8% of dysplastic lesions and 47% of hepatocellular carcinomas. At least one marker was detected in 75% of dysplastic lesions and 100% of hepatocellular carcinomas. The three markers were more frequently expressed in areas of small cell than of large cell change (34 vs 10%). No correlation was found with the grade of dysplasia, the occurrence of arterialization and the association with hepatocellular carcinoma. CONCLUSIONS: Alterations in the hepatic microcirculation comparable to those observed in hepatocellular carcinoma are present in a significant proportion of dysplastic lesions of the liver and may be indirect markers of the process of liver carcinogenesis.

Transjugular intra-hepatic portosystemic shunt for refractory variceal bleeding.

BACKGROUND: The most dramatic complication of portal hypertension in cirrhotic patients is oesophageal variceal bleeding. Moreover, patients with bleeding unresponsive to medical and endoscopic treatment have a poor prognosis. OBJECTIVE: The aim of this study was to evaluate the efficacy of early transjugular intra-hepatic portosystemic shunt (TIPS) in patients with refractory variceal bleeding. PATIENTS AND METHODS: TIPS was performed for 28 patients (17 were stage Child C), successfully in 26. Variceal bleeding was controlled in all but one successfully stented patient. RESULTS: There was no mortality associated with the procedure. The two patients with a failure of TIPS insertion died of persistent bleeding in the first 48 h after failed TIPS. The 40-day mortality rate was 25%. Five patients died (one from persistent bleeding from gastric varices and four from multi-organ failure). Using multivariate analysis, the only independent factor associated with early mortality was the total bilirubin value. Fifteen surviving patients were listed for liver transplantation: four deaths occurred, eight patients were transplanted in the 6 months after TIPS and three are still waiting. Among the six patients who survived but were ineligible for transplantation, two died and four are still alive. Two episodes of early rebleeding and eight of late rebleeding occurred. Actuarial survival was 75% at one year and 52% at two years. CONCLUSIONS: Early TIPS is an effective rescue therapy for controlling refractory variceal bleeding.

Orthotopic liver transplantation for idiopathic portal hypertension: indications and outcome.

BACKGROUND: Idiopathic portal hypertension is a rare clinical syndrome which may be associated with a spectrum of histological lesions, including nodular regenerative hyperplasia and incomplete septal cirrhosis. Here, we report eight adult patients with idiopathic portal hypertension who experienced an unusually severe clinical evolution characterized by the development of progressive hepatic failure requiring orthotopic liver transplantation. Our aims are: (a) to stress the distinctive clinical presentation of these patients, (b) to describe their biological and histopathological features, and (c) to evaluate the results of orthotopic liver transplantation in this rare indication. METHODS: Complete clinical charts and histological data were available in all patients. All patients were male. Their age at diagnosis ranged from 17 to 59 years. Complications of portal hypertension revealed the disease in all cases. Medical treatment was performed in all patients and portosystemic shunt in three. RESULTS: The development of progressive hepatic failure led to the indication of liver transplantation after a delay ranging from 3 to 10 years. Explanted livers showed pure nodular regenerative hyperplasia in three patients and incomplete septal cirrhosis in five. Recovery was uneventful. All patients are alive, without recurrence of the disease. CONCLUSIONS: This report points to the existence of severe cases of idiopathic portal hypertension occurring without underlying or associated systemic disease and characterized by a poor clinical course and requiring liver transplantation.

Intra-arterial iodine 131-labeled lipiodol as adjuvant therapy after curative liver resection for hepatocellular carcinoma: a phase 2 clinical study.

HYPOTHESIS: Intra-arterial lipiodol labeled with iodine 131 ((131)I-lipiodol) can be safely used as adjuvant therapy following curative liver resection for hepatocellular carcinoma (HCC). DESIGN: Phase 2 pilot study. SETTING: Large teaching hospital. PATIENTS: Twenty-eight patients (24 men and 4 women; median age, 61.5 years; range, 33-75 years) were treated from January 1991 to June 1997. The liver was cirrhotic in 7 cases and noncirrhotic in 21 cases. An equal number of 14 patients underwent a major and a minor resection, all with clear margins. Median diameter of solitary tumors or the larger tumor when multiple tumors occurred was 5.5 cm (range, 2.5-29 cm). Tumor encapsulation was present in 12 cases and absent in 16 cases. After informed consent, patients who had no evidence of residual or recurrent tumor on computed tomographic (CT) scan and no sign of liver failure 2 to 3 months after curative resection for HCC were included in the trial. Complete follow-up was obtained (median, 51 months; range, 5-93 months). INTERVENTIONS: A 1110-MBq dose of (131)I-lipiodol was administered into the hepatic artery using the Seldinger technique. Patients were kept in a radio-protected room for 5 days. Postinjection radioactive whole scintiscan was performed at 5 days and an abdominal CT scan at 1 month after the injection. A second injection was performed in 16 patients 2 years later using the same protocol. MAIN OUTCOME MEASURE: Procedure safety. RESULTS: All patients experienced transient fever during the first 12 hours following injection. There were no noted adverse clinical effects or significant alteration in hepatic function due to the procedure or at immediate and late follow-up. The radioactive scan demonstrated an intense liver uptake, which was homogeneous in 19 cases and heterogeneous in 9. Mild detectable thyroid and lung uptake occurred in 50% of cases. No lipiodol liver fixation was observed on the 1-month CT scan. At the time of follow-up, 6 patients had died and 12 had developed recurrences, with 5 of the 6 deaths belonging to the recurrent group. Sixteen patients remained disease free. The median time to detected recurrence was 28 months (range, 12-62 months). Overall survival rates were 86% at 3 years and 65% at 5 years. CONCLUSIONS: This pilot study failed to demonstrate any clinically significant adverse effect of adjuvant therapy by intra-arterial (131)I-lipiodol after curative liver resection for HCC. Long-term survival compares favorably with those undergoing only surgery and suggests a benefit in lowering tumor recurrence. A randomized, multicenter, prospective trial comparing patients treated with intra-arterial (131)I-lipiodol with a nontreated control group seems appropriate.

Familial occurrence of nodular regenerative hyperplasia of the liver: a report on three families.

BACKGROUND/AIMS: Nodular regenerative hyperplasia of the liver is a histological lesion usually associated with systemic diseases, haematological malignancies, or drugs. Its prognosis depends on portal hypertension, which usually is well tolerated and requires medical management only. PATIENTS: Three unrelated families, in which two sibling adult male patients presented with nodular regenerative hyperplasia of the liver, were studied. METHODS: Complete clinical charts and liver biopsy specimens were available for all patients. In addition, explanted livers were available for examination for the two transplanted patients. RESULTS: There was no evidence of any of the various clinical situations known to be associated with nodular regenerative hyperplasia of the liver. Portal hypertension was severe, requiring surgical treatment in two cases. Renal lesions were present in three patients. In two patients, progressive evolution to liver atrophy and hepatic failure, associated with renal failure, led to combined liver and renal transplantation. CONCLUSIONS: This report describes the existence of familial cases of nodular regenerative hyperplasia of the liver, occurring without underlying or associated systemic disease, characterised by a poor clinical course and often associated with progressive renal failure.

[The Budd-Chiari syndrome (hepatic vein obstruction). The diagnostic and therapeutic management of acute and subacute forms]. / Syndrome de Budd-Chiari (obstruction des veines hépatiques). Prise en charge diagnostique et thérapeutique des formes aiguës et subaiguës.

EARLY DIAGNOSIS: The Budd-Chiari syndrome results from an obstruction of the suprahepatic venous drainage. The condition spontaneously evolves towards liver fibrosis and death. Early diagnosis is thus of prime importance to initiate adapted treatment promptly. EXPLORATIONS: Color-coded and pulsed Doppler coupled with ultrasonography is the key to positive diagnosis. Magnetic resonance imaging may provide further precision. DECONGESTION OF THE LIVER: As the hepatic lesions are reversible, satisfactory drainage must be achieved as rapidly as possible, either by percutaneous puncture or surgery. The problem is to control the underlying hematology disease to prevent recurrent venous thrombosis, generally the cause of treatment failure. PREVENTIVE ANTICOAGULATION: Effective anticoagulation using low-molecular-weight heparin, which appears to be more adapted than standard heparin, must be achieved prior to any decongestion procedure. Long-term management requires anti-vitamin K therapy if the risk of thrombosis persists.

Prospective evaluation of transnasal esophagogastroduodenoscopy: feasibility and study on performance and tolerance.

BACKGROUND: With a pediatric endoscope, esophagogastroduodenoscopy (EGD) can be performed via a nasal route in adults. To evaluate this new procedure, we conducted a randomized comparative study of the feasibility of diagnostic transnasal EGD and assessed the factors influencing its quality and tolerance (endoscope diameter or route). METHODS: Transnasal EGD was attempted in 100 patients to assess its feasibility. For the analysis of quality and tolerance, 150 patients were randomized as follows into 3 groups according to the route of examinations: (1) oral route with 9.8 mm diameter standard videoendoscope; (2) oral route with 6.0 mm diameter pediatric videoendoscope; (3) transnasal route with 6.0 mm diameter pediatric videoendoscope. The operator assessed the quality of examination by standard scores. Patients quantified pain intensity, nausea, and choking sensation. RESULTS: Transnasal EGD was feasible in 82% of patients. The quality of the examination was significantly lower with pediatric endoscope. No difference was noted concerning pain intensity, but nausea and choking sensation were significantly reduced when the nasal route was used. CONCLUSIONS: Transnasal EGD is feasible in the routine practice of diagnostic EGD. The nasal route, and not endoscope diameter (6.0 mm vs 9.8 mm diameter), is the determining factor that explains increased patient tolerance during transnasal EGD. Technical improvements in pediatric videoendoscopes are required.

Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement.

BACKGROUND & AIMS: Hepatic involvement in hereditary hemorrhagic telangiectasia is common but often asymptomatic. However, in some cases, the vascular lesions that involve the liver may lead to high-output cardiac failure and pulmonary hypertension that is predominant over hepatobiliary manifestations. Liver transplantation and treatment of these complications are described and discussed in this article. METHODS: Three patients with hereditary hemorrhagic telangiectasia and hepatic involvement received transplants. They had pulmonary hypertension and chronic right-sided heart failure caused by disseminated intrahepatic telangiectasias with shunts between the hepatic artery and hepatic veins or portal vein. Left-to-right intrahepatic shunt output was estimated to range between 51% and 57.5% of cardiac output. RESULTS: Hyperdynamic circulation disappeared after liver transplantation in all patients. Results of computed tomography and right-sided heart catheterization performed 6 months later were normal. Follow-up periods currently are 65, 53, and 29 months, and each patient continues to be asymptomatic. CONCLUSIONS: This report suggests that liver transplantation can be considered as an alternative and successful curative treatment that may prevent the irreversible evolution of cardiopulmonary disease.

[Late cryptococcal meningitis after liver transplantation]. / Cryptococcose neuro-méningée tardive après transplantation hépatique.

We report a case of cryptococcal meningitis, eight years after liver transplantation for primary biliary cirrhosis. Detection of the cryptococcal antigen in serum and cerebrospinal fluid appears to be essential for initial diagnosis and follow-up. Oral fluconazole treatment alone can be effective, when given for a very long period to prevent relapse.

Reversal of early acute rejection with increased doses of tacrolimus in liver transplantation: a pilot study.

BACKGROUND: In this pilot study, we present the results of treatment of early (3 months after liver transplantation) acute rejection episodes by increasing only the tacrolimus doses. METHODS: Ten patients who received tacrolimus as primary treatment experienced acute mild (one case), moderate (four cases), or severe (five cases) rejection episodes. Tacrolimus dosing was increased 1-2 mg every 1 or 2 days until hepatic enzymes started to improve. Steroid basic daily doses were kept unchanged. RESULTS: With the daily dose of tacrolimus increased by a median 1.89-fold (range: 1.2-5), alanine aminotransferase, bilirubin, and gamma-glutamyltranspeptidase levels rapidly reached normal values within the first month. During a median follow-up time of 19.5 months (range: 14-24), none of the 10 patients died or lost their graft. Control liver biopsies were done 13.5 months (range: 7-19) after rejection episode in all patients, and none demonstrated evidence of rejection or sequela. CONCLUSION: This pilot study suggests that increasing tacrolimus dosage could be considered as treatment against early acute rejection episodes including the severe grade.

[Adrenal metastases of hepatocellular carcinoma. Therapeutic options]. / Métastases surrénaliennes des carcinomes hépatocellulaires. Options thérapeutiques.

AIM OF THE STUDY: The aim of this study was to evaluate the therapeutic modalities, particularly surgical treatment, for adrenal metastasis of hepatocellular carcinomas. PATIENTS AND METHODS: This series included 13 patients (mean age: 64 years) with hepatocellular carcinoma on cirrhotic liver (n = 8) or healthy liver (n = 5). The adrenal metastasis was synchronous in four cases, metachronous in nine, unilateral in ten cases, and bilateral in three. Resection of the adrenal metastasis was performed in seven patients, combined with the resection of the hepatic carcinoma in three cases or secondarily performed in four. The metastasis was not resected in six patients because of poor liver function or poor patient conditions; two patients were treated with percutaneous ethanol injection, one with radiation and three received only a symptomatic treatment. RESULTS: After adrenalectomy combined with liver resection, two patients died in the postoperative course in relation with pulmonary embolism (n = 1) or acute pancreatitis (n = 1). The mean survival in the five other patients was 38 months after the adrenalectomy and 58.6 months after the liver resection. After percutaneous ethanol injection, one patient survived 47 months and the other one 7 months only. After radiation, the patient survived 18 months. After symptomatic treatment, the mean survival was only 7.3 months. CONCLUSION: The present data suggest that adrenal metastasis, either isolated or associated with a well-controlled intrahepatic recurrence, could be treated surgically when the resection is technically feasible. This aggressive management seems the only chance to offer a long-term survival to selected patients.