Regression of new-onset diabetes mellitus after conversion from tacrolimus to cyclosporine in liver transplant patients: results of a pilot study.

INTRODUCTION: New-onset diabetes mellitus (NODM) has important implications for long-term outcome following liver transplantation. AIM: To evaluate the impact of conversion from tacrolimus to cyclosporine in liver transplant patients presenting NODM. METHOD: In a 12-month pilot study, 39 liver transplant patients with NODM were converted from tacrolimus to cyclosporine. Most patients (59%) were receiving antidiabetic therapy (18% insulin, 41% oral) and all patients had received dietary advice prior to the study. RESULTS: At month 12, NODM had significantly resolved (FBG<7 mmol/L without treatment) in 36% of patients (95% CI 20.8-51.0%). In the 16 patients not receiving antidiabetic drugs at baseline, mean FBG decreased from 8.1 mmol/L to 6.6 mmol/L (P=0.008) and mean HbA(1c) decreased from 6.4 to 6.0% (P=0.05). Steroids were stopped rapidly in the nine patients receiving steroids at inclusion but NODM resolution was observed in only one of these nine patients. No significant factors were identified that could have affected NODM resolution. There were three episodes of biopsy-proven acute rejection (7.7%), no graft losses and one death. Overall, cyclosporine tolerance was good with no significant change in creatinine clearance at month 12. Total cholesterol increased from 4.6 mmol/L to 5.1 mmol/L (P<0.001). CONCLUSIONS: These results suggest that liver transplant patients with NODM may benefit from conversion to cyclosporine from tacrolimus through improved glucose metabolism. Confirmation in a prospective, randomized comparative study is required.

Histological benefit of retreatment by pegylated interferon alfa-2b and ribavirin in patients with recurrent hepatitis C virus infection posttransplantation.

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.

Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence.

BACKGROUND AND AIMS: A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin. However, the long term benefit of antiviral therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in patients with HCV recurrence. This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy. PATIENTS AND METHODS: Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy (interferon (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12 months. Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy. Serum alanine aminotransferases were assessed every three months during the observation period. Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up, and protocol biopsy procedures were performed routinely every year. Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue samples. RESULTS: At the end of antiviral therapy, the sustained response rate was 26%. A complete response (normal serum alanine aminotransferase level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three years after the end of treatment. A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy showed normal or near normal histological findings. After three years of follow up, the total Knodell score was 3.2 (range 1-8) versus 8.3 (range 5-12) before treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 (93%) patients tested. CONCLUSION: In patients with biochemical and virological responses induced by ribavirin and interferon, a complete response was sustained in 93% for at least three years after cessation of therapy. This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement.

[Intussusception of the small intestine due to Peutz-Jeghers syndrome: a case report and review of the literature]. / Invagination intestinale dans le cas d'un syndrome de Peutz-Jeghers et revue de la littérature.

One case of small bowel's intussuception has been found in one patient with abdominal pains. Since 13 years this patient has a Peutz-Jeghers syndrome. A resection of the small bowel has been performed followed by total intraoperative enteroscopy. Besides small bowel, Peutz-Jeghers syndrome can affect many organs with an increased risk for cancer for patients affected by this genetic disease.

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.

Small nodule detection in cirrhotic livers: evaluation with US, spiral CT, and MRI and correlation with pathologic examination of explanted liver.

PURPOSE: The purpose of this work was to evaluate the detection and characterization of nodules > or = 8 mm and small hepatocellular carcinomas (HCCs) in liver cirrhosis. METHOD: Pathologic examination and results of US, helical CT, and dynamic MRI with gadolinium were compared after orthotopic liver transplantation (OLT) of 43 cirrhotic patients. Nodules were classified as macroregenerative nodules (MRNs), borderline nodules (BNs), and HCC. RESULTS: Pathologic examination classified 69 nodules: 50 MRNs, 6 BNs, and 13 HCCs. Sensitivities of MRN, BN, and HCC detection were, respectively, for US imaging 2% (1/50), 33.3% (2/6), and 46.2% (6/13); for helical CT 2% (1/50), 50% (3/6), and 53.8% (7/13); and for MRI 42% (21/50), 50% (3/6), and 76.9% (10/13). MRI detected 21 MRNs. They presented on T1/T2-weighted images as hyperintense/hypointense (n = 8), hyperintense/isointense (n = 7), hypointense/hypointense (n = 4), hypointense/isointense (n = 1), and hypointense depicted only on echo planar imaging (n = 1). The three detected BNs were hyperintense/hypointense nodules. The 10 detected HCCs appeared hyperintense/isointense (n = 7), hyperintense/hypointense (n = 2), and hypointense/isointense (n = 1). None of the MRNs but eight HCCs and one BN were enhanced after gadolinium injection. CONCLUSION: Contrast-enhanced MRI is the most sensitive technique for detecting liver nodules. No MR signal intensity pattern characteristic of small HCCs enables differentiation from benign nodules, however. Gadolinium enhancement is the most sensitive and specific characteristic of HCC.

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.

Anti-hepatitis C virus core IgM antibodies correlate with hepatitis C recurrence and its severity in liver transplant patients.

BACKGROUND: The significance of immunoglobulin (Ig) M antibody to hepatitis C virus (HCV) core antigen was studied in 60 patients with HCV infection after orthotopic liver transplantation (OLT) diagnosed by polymerase chain reaction. METHODS: Patients were followed up for a mean of 28 months after transplantation. Sera collected three months before transplantation, and one and 12 months after transplantation were analysed for anti-HCV core IgM (HCV-IgM EIA 2.0 assay). After OLT protocol biopsies, procedures were performed routinely every six months. Semiquantitative histopathological assessment of allograft hepatitis was performed using Knodell's score. The results were correlated with clinical features, liver histology findings, and virological features, such as genotype and viraemic levels assessed by a branched DNA assay. RESULTS: One year after liver transplantation, 29/60 (48%) patients had chronic hepatitis on graft biopsy. The presence of anti-HCV core IgM one month (p=0.004) and 12 months (p=0.003) after OLT was positively correlated with recurrence of chronic hepatitis. The positive predictive value of anti-HCV core IgM detected one month after transplantation was 0.88. A significant relationship was observed between severity of graft disease and presence of anti-HCV core IgM 12 months after transplantation. The mean Knodell score was 8.9 in anti-HCV core IgM positive patients compared with 3.6 in those who were anti-HCV core IgM negative (p=0.001). The presence of IgM anti-HCV did not correlate with serum HCV RNA level or HCV genotype. CONCLUSION: We confirm that the presence of anti-HCV core IgM after OLT is a marker of HCV induced graft damage. The recurrence and severity of HCV hepatitis in patients undergoing OLT for HCV cirrhosis is related to the presence of anti-HCV core IgM after liver transplantation. These findings have diagnostic relevance and confirm that measurement of IgM anti-HCV core may help to better monitor the treatment of HCV recurrence after transplantation.

[Peritonitis with Mycobacterium avium complex in a patient with alcoholic cirrhosis]. / Infection du liquide d'ascite à Mycobacterium avium complex chez un malade ayant une cirrhose alcoolique.

Before highly active antiretroviral therapy were available, disseminated Mycobacterium avium complex infection was common in adults with HIV. Diagnosis was often made by blood culture in these immunocompromised patients. Although Mycobacterium avium complex disease can involve any organ of the body, infection of serosal surfaces is very rare. Mycobacterium avium complex peritonitis is rare and usually occurs in immunocompetent patients with chronic ambulatory peritoneal dialysis. We report a case of Mycobacterium avium complex peritonitis in a patient with alcoholic cirrhosis with no evidence of HIV infection. Diagnosis was made by culture of a lymphocytic ascites which showed Mycobacterium avium complex at 4 weeks. Interestingly, blood and hepatic cultures remained negative. At three months, marked improvement occurred with antimycobacterial treatment, so that orthotopic liver transplantation could be performed.

Hemodynamic profiles during piggyback liver grafts using arterial or portal revascularization.

BACKGROUND: The order of revascularization in human liver grafts is still discussed. This study tries to answer this question in terms of hemodynamic data. STUDY DESIGN: Fifty-nine patients were randomized in this study to compare hemodynamic data just before and 15 minutes after revascularization of liver grafts in relation to first hepatic artery (n = 29) or first portal vein (n = 30) revascularization procedure. RESULTS: Hemodynamic variations were significantly greater in the portal vein group than in the hepatic artery group in terms of mean arterial pressure, cardiac index, central venous pressure, pulmonary capillary pressure, and systemic vascular resistance. The latter decreased from 741.8 +/- 390.3 to 659.9 +/- 411.1 dynes/ cm5 (NS) in the hepatic artery group versus 807.7 +/-336.7 to 439.7 +/- 215 dynes/cm5 (p < 0.05) in the portal vein group. Clinical results and postoperative complications, graft characteristics, patient survival, and graft survival were not significantly different between the groups. CONCLUSIONS: Initial arterial revascularization of the liver graft leads to a more stable hemodynamic profile during revascularization of the liver graft after vascular unclamping. This technique is always feasible and has become our reference procedure.

Recurrence of hepatocellular carcinoma as a mixed hepatoblastoma after liver transplantation.

BACKGROUND: Hepatoblastoma is an exceptional cause of primary malignant liver tumour in the adult. PATIENT: The case is reported of an adult patient transplanted for alcoholic cirrhosis complicated by multifocal hepatocellular carcinoma in whom a recurrence in the form of a mixed hepatoblastoma invading the whole transplanted liver developed three months after liver transplantation. METHODS: Complete clinical, histopathological, and immunohistochemical data were reviewed. RESULTS: The recurrent tumour invaded the whole liver. The major component was a mixed hepatoblastoma, with an epithelial component expressing cytokeratin and a mesenchymal component expressing vimentin. The tumour also contained a minor hepatocarcinomatous component expressing alpha fetoprotein. The rapid growth of the tumour prevented any attempt at treatment. Although direct evidence is lacking, the most likely hypothesis to explain the observations is a marked phenotypic change in the initial malignant population at recurrence. CONCLUSION: This case supports a possible filiation between hepatocellular carcinoma and hepatoblastoma in adults.

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Hepatitis C virus recurrence after liver transplantation.

Cirrhosis due to hepatitis C virus (HCV) is now the most common indication of liver transplantation in Western Europe and the United States. In the absence of effective prophylaxis, recurrent HCV infection is almost inevitable. Though the natural history and intermediate term outcome of recurrent HCV are now better documented, those factors which may influence the recurrence of hepatitis and consequent progression of graft disease remain unclear. Interferon (IFN) as a sole agent for the treatment of recurrent infection has proved unsatisfactory. Early intervention with a combination of IFN and ribavirin seems promising, and this approach may prevent or delay progression of HCV related graft disease after liver transplantation.

Treatment of recurrent hepatitis C following liver transplantation.

Cirrhosis due to hepatitis C virus infection is now the most common indication for liver transplantation in Western Europe and the United States. In the absence of effective prophylaxis, recurrent hepatitis C virus infection is almost inevitable. Although the natural history and intermediate-term outcome of recurrent infection with hepatitis C virus are now better documented, factors that may influence the recurrence of hepatitis and consequent progression of graft disease remain unclear. Interferon used as a single agent for the treatment of recurrent infection has proven unsatisfactory. Early intervention for recurrent infection with the combination of interferon and ribavirin appears promising, and this approach may prevent or delay progression of hepatitis C virus-related graft disease after liver transplantation.

Results of orthotopic liver transplantation for liver cirrhosis in the presence of incidental and/or undetected hepatocellular carcinoma and tumour characteristics.

Orthotopic liver transplantation (OLT) for liver cirrhosis in the presence of hepatocellular carcinoma (HCC) is based on tumour number and size. The high incidence of undetected HCC before OLT has been reported previously. The object of this work to report the results of OLT for liver cirrhosis in the presence of incidental and/or undetected HCC and tumour characteristics. From 1985 to 1996, 334 patients received OLT. Two groups of patients were studied; group 1 (G1) where HCC was diagnosed on radiological examination before OLT (n = 13, mean age 53.8 +/- 8.1 years), and group 2 (G2), where HCC was diagnosed on pathological review (n = 13, mean age 53.3 +/- 6.1 years). Indications for OLT were (G1/G2) hepatitis C = 6/8, hepatitis B = 5/2, alcoholic = 2/3. There was no statistically significant difference in alpha-foetoprotein levels between both groups. Pathological review showed 26 and 30 HCC with a mean size of 1.6 +/- 0.8 and 1.6 +/- 1.2 cm (P > 0.05) in G1 and G2, respectively. Tumour stagings were (G1/G2) stage I = 6/2, stage II = 4/6, stage III = 2/3, stage IVa = 1/2. We had two (G2) hospital and three (G1) later mortalities; none had HCC recurrence. The other patients are alive and recurrence free. Reinforced immunosuppression related to acute or chronic rejection treatment was not associated with HCC recurrence. The 5-year actuarial survival rates were 76% for G1 and 85% for G2 (P > 0.05). Our study revealed that long-term survival can be achieved with liver transplantation in the presence of HCC in carefully selected patients.

Influence of systematic echodoppler arterial survey on hepatic artery thrombosis after liver transplantation in adults.

Hepatic artery thrombosis after liver transplantation remains a major problem which may lead to graft loss and retransplantation. Hepatic artery diseases were compared in two matched groups of liver grafted patients. In Group I (67 patients), echodoppler examinations of the graft hepatic artery were carried out after clinical or biological abnormalities became evident. In Group II (85 patients), echodoppler examinations were systematically made during the follow-up at 2 weeks, 1, 3, 6, and 12 months after liver transplantation. In cases of an abnormal echodoppler examination, arteriography was carried out in order to confirm hepatic artery stenosis and to perform endoluminal angioplasty. In Group I, echodoppler examinations revealed no arterial blood flow in three cases and reduction of hepatic blood flow in two cases. Hepatic artery thromboses were always confirmed by angiography, in the latter two cases, a collateral arterial revascularization of the graft was developed. In this group, two retransplantations, one choledocojejunostomy, and four percutaneous radiological biliary drainages were necessary. In Group II, echodoppler results showing a resistive index below 0.5 and a systolic acceleration time above 0.08 s involved 13 arteriographies. Ten stenoses were diagnosed without any biological abnormalities. Nine endoluminal angioplasties were made without any complication. There was no recurrence of stenosis. One pseudoaneurysm of the femoral artery was cured by compression. The early and non-aggressive detection of hepatic artery stenoses after liver transplantation by echodoppler allows treatment by angioplasty in order to prevent hepatic artery thrombosis and reduce retransplantation.