30-yr course and favorable outcome of alveolar echinococcosis despite multiple metastatic organ involvement in a non-immune suppressed patient.

We report the 30-yr history of a well-documented human case of alveolar echinococcosis, with a lung lesion at presentation followed by the discovery of a liver lesion, both removed by surgery. Subsequently, within the 13 years following diagnosis, metastases were disclosed in eye, brain and skull, as well as additional lung lesions. This patient had no immune suppression, and did not have the genetic background known to predispose to severe alveolar echinococcosis; it may thus be hypothesized that iterative multi-organ involvement was mostly due to the poor adherence to benzimidazole treatment for the first decade after diagnosis. Conversely, after a new alveolar echinococcosis recurrence was found in the right lung in 1994, the patient accepted to take albendazole continuously at the right dosage. After serology became negative and a fluoro-deoxy-glucose-Positron Emission Tomography performed in 2005 showed a total regression of the lesions in all organs, albendazole treatment could be definitively withdrawn. In 2011, the fluoro-deoxy-glucose-Positron Emission Tomography showed a total absence of parasitic metabolic activity and the patient had no clinical symptoms related to alveolar echinococcosis.The history of this patient suggests that multi-organ involvement and alveolar echinococcosis recurrence over time may occur in non-immune suppressed patients despite an apparently "radical" surgery. Metastatic dissemination might be favored by a poor adherence to chemotherapy. Combined surgery and continuous administration of albendazole at high dosage may allow alveolar echinococcosis patients to survive more than 30 years after diagnosis despite multi-organ involvement.

Immediate listing for liver transplantation versus standard care for Child-Pugh stage B alcoholic cirrhosis: a randomized trial.

BACKGROUND: Liver transplantation improves survival of patients with end-stage (Child-Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain. OBJECTIVE: To compare the outcomes of patients with Child-Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease. DESIGN: Randomized, controlled trial. SETTING: 13 liver transplantation programs in France. PATIENTS: 120 patients with Child-Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation. INTERVENTIONS: Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients). MEASUREMENTS: Overall and cancer-free survival over 5 years. RESULTS: Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [CI, 2.395 to 24.154]), recovery from Child-Pugh stage C (hazard ratio, 7.633 [CI, 2.392 to 24.390]), and baseline Child-Pugh score less than 8 (hazard ratio, 2.664 [CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care. LIMITATION: Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings. CONCLUSION: Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child-Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer. FUNDING: The French National Program for Clinical Research.

[Alveolar echinococcosis: a disease comparable to a slow growing cancer]. / L'échinococcose alvéolaire: une maladie comparable à un cancer du foie à marche lente.

Alveolar echinococcosis, a parasitic disease due to the larval stage of the cestode Echinococcus multilocularis, is initially located in the liver in 97% of cases. Progression is very slow and the disease remains silent for many years. The developing larva behaves like a slow-growing liver tumor that gradually invades the liver parenchyma, vessels and bile ducts. Marked granulomatosis around the larva, and the subsequent strong reactive fibrosis, contribute to the severity of the disease. Gradual extension to adjacent organs and distant metastases due to haematogenous spread can also occur. Purely extrahepatic alveolar echinococcosis is rare, but physicians in endemic areas should be aware of this possibility. Diagnostic methods have dramatically improved over the past twenty years. The clinical presentation used to be similar to that of liver cancer, with slowly progressivejaundice (due to involvement of the hilum), huge, hard and irregular hepatomegaly, and a chronic Budd-Chiari syndrome due to hepatic vein involvement. Currently, with extensive use of abdominal ultrasonography, alveolar echinococcosis is commonly diagnosed when still asymptomatic. Alveolar echinococcosis may also be revealed by a complication, such as cholangitis due to communication between the parasite mass and the lumen of a bile duct or to pigment stones accumulating above a parasitic biliary stenosis; liver abscess related to centro-parasitic necrosis; or hematemesis due to esophagal varices in case of portal vein involvement. Metastases, especially in the lungs, reveal the disease in 5% of cases.

Granulomatous hepatitis and hemophagocytic syndrome after bacillus Calmette-Guerin bladder instillation.

Intravesical instillations of bacillus Calmette-Guérin are frequently used for treating superficial bladder carcinoma which is considered a safe treatment. We describe an unusual complication with hemophagocytosis and granulomatous hepatitis. Prompt diagnosis and treatment with corticosteroids, anti-tuberculous agents and intravenous immunoglobulins led to a rapid recovery.

[Complementary treatments of chronic viral hepatitis C]. / Traitements complémentaires de l'hépatite chronique virale C.

Pegylated interferon and ribavirin combination therapy represent the standard-of-care treatment for chronic hepatitis C, that allows to cure more than half of the patients. However, the success of this bitherapy is in balance with numerous side effects, especially hematologic and psychiatric. This review is focused on complementary treatments (erythropoietin, G-CSF, vitamin E, glutathion, ursodeoxycholic acid and antidepressants) likely to bring a benefit in maintaining adequate interferon and ribavirin dosages and in improving quality of life. This analysis has been performed by using the Medline(R) data base and with data from laboratories which commercialized these molecules. Erythropoietin, G-CSF and antidepressants are the best tools to optimize the bitherapy in its dose and its duration while privileging the quality of life of HCV-infected patients.

Imaging aspects and non-surgical interventional treatment in human alveolar echinococcosis.

Alveolar echinococcosis (AE) of the liver caused by the metacestode of the fox tapeworm Echinococcus multilocularis is characterized by a multivesicular structure surrounded by an extensive fibro-inflammatory host reaction. The lesions behave like a slow-growing liver cancer, without sharp limits between the parasitic tissue and the liver parenchyma. Invasion of biliary and vascular walls is another hallmark of this severe disease. Moreover, the poor vascularization of the parasitic mass often leads to necrosis in the central part of the lesion. This explains why liver abscess due to superimposed bacterial infection of the necrotic area may occur in this disease. Currently, a range of imaging techniques can be used at the different stages of management of AE. For diagnosis, ultrasonography remains the first line examination. For a more accurate disease evaluation, aiming to guide the surgical strategy, computerized tomography, Magnetic Resonance (MR) imaging, including cholangio-MR imaging are of importance, providing useful complementary information. More recently, Positive-Emission Tomography using [18F] fluoro-deoxyglucose has been developed for the follow-up of inoperable AE patients under long-term benzimidazoles therapy. This approach seems very promising to assess inflammatory activity and thereby to indirectly depict parasitic activity. Non-surgical interventional procedures, mainly percutaneous biliary and/or centro-parasitic abscesses drainages, are currently a major aspect in the care of incurable AE patients and have largely contributed to the improvement of survival in this situation during the past 20 years. They may also be used as a bridge before a curative surgical procedure in symptomatic patients presenting a life-threatening bacterial and/or fungal infection. It is also very useful in inoperable patients to overcome similar infectious episodes.

Place of residence and distance to medical care influence the diagnosis of hepatitis C: a population-based study.

BACKGROUND/AIMS: In France, geographic access to medical care may affect the diagnosis of hepatitis C. The aims of this study were to compare the detection rates of hepatitis C in urban and rural areas after adjusting for distance to medical care, and evaluating the impact of the place of residence on patients' clinical characteristics. METHODS: Between 1994 and 2001, 1938 newly detected cases were recorded in a French population of 1,005,817 inhabitants. Age and sex-adjusted detection rates for 10(5) inhabitants were estimated for urban and rural areas and for classes of distance to the nearest practitioner. RESULTS: Detection rates were lower in rural than in urban areas [14.1, (95CI: 12.5-15.7) versus 24.7, (95CI: 23.5-26.0)] and decreased as the distance to the general practitioner increased [27.0, (95CI: 25.5-28.4) versus 13.7, (95CI: 12.1-15.3) for a cutoff value of 1.5 km]. In multivariate analyses, detection rates were only influenced by the distance to general practitioner. Hepatocellular carcinoma at diagnosis was more frequent among rural than among urban patients (adjusted OR = 2.28, 95CI: 0.97-5.39, P = 0.059). CONCLUSIONS: A poorer geographic access to care explained the lower detection of hepatitis C in rural areas. Hepatocellular carcinoma was more frequent in rural patients. It may result from later detection and/or involvement of environmental factors on hepatocarcinogenesis.

Liver transplantation for cardiac failure in patients with hereditary hemorrhagic telangiectasia.

Liver involvement in hereditary hemorrhagic telangiectasia may lead to high-output cardiac failure. Few data have been reported on orthotopic liver transplantation (OLT) for these patients. In this paper, we describe two patients treated by OLT as a salvage procedure for cardiac failure, and we review literature on this subject. Our two patients resumed normal cardiac function after OLT. This procedure appears to be a promising therapy with good long-term results despite dissection difficulties encountered due to the collateral arterial network reorganization.

Predictive factors of alcohol relapse after orthotopic liver transplantation for alcoholic liver disease.

OBJECTIVES: The objective of this prospective study was to determine whether sociological and/or alcohol-related behavioral factors could be predictive of relapse after orthotopic liver transplantation for alcoholic liver disease. METHODS: Fifty-five liver-transplanted patients out of a series of 120 alcoholic cirrhotic patients were enrolled in a randomized prospective study. This study was initially designed to compare the 2 year survival in intent-to-transplant patients versus in-intent-to-use conventional treatment patients. For all patients, an identical questionnaire was completed at inclusion, and every 3 months for 5 years to collect data on alcohol-related behavior factors. RESULTS: Fifty-one patients fulfilled the criteria for the study. The mean follow-up was 35.7 months (range: 1-86). Rate of alcohol relapse was 11% at one year and 30% at 2 years. Alcohol intake above 140 g a week was declared by 11% and 22% of patients at one and 2 years, respectively. The only variable leading to a significantly lower rate of relapse was abstinence for 6 months or more before liver transplantation (23% vs 79%, P=0.0003). This variable was also significant for patients whose alcohol intake was greater than 140 g per week (P=0.003) (adjusted relative risk=5.5; 95%CI=1.3-24.5; P=0.02). Multivariate analysis (Cox model) showed that abstinence for 6 months or more before liver transplantation was the unique predictive variable. CONCLUSION: In this prospective study of 51 patients transplanted for alcoholic liver disease, abstinence before liver transplantation was the only predictive factor of alcohol relapse after liver transplantation.

Management of hepatitis C patients: a French population-based study.

AIMS: Our aim was to assess the proportion of patients in a well-defined population reaching specialized medical care after hepatitis C diagnosis. METHODS: Hepatitis C-positive patients recorded in the population-based registry of Cote-d'Or, an administrative district in France, constituted the study population. RESULTS: Between 1994 and 1999, new hepatitis C-positive serology was diagnosed in 847 patients, of whom 690 were eligible for this study. A total of 135 patients had not been given specialized medical care after diagnosis; among them, 50.4% had a normal serum alanine transferase level at diagnosis, 62.2% had risk factors related to lifestyle (drug addiction, sexual risk...), and 26.7% were current alcoholics. The 555 other patients were involved in specialized medical care after diagnosis: 42.7% had a liver biopsy and 27.0% were treated. Treatment was carried out more often in males than in females (OR: 1.67; P<0.005), and in patients less than 65 years old (OR: 2.94; P<0.0002). Nearly 30.5% of patients with a Metavir score greater than A1F1 did not undergo treatment. CONCLUSION: This study shows that in a general population at least one patient out of five with hepatitis C infection remains outside the health care system. It also reveals that management practices vary with gender. Further surveys are needed to better understand this phenomenon.

[Is chronic hepatitis C treatment as efficient in the general population as in randomised trials?]. / Le traitement de l'hépatite chronique C est-il aussi efficace dans la population générale que dans les essais randomisés?

AIMS: The aim of this population-based study was to determine the effectiveness of antiviral therapy in non selected chronic hepatitis C patients. METHODS: The study was performed in all new patients with anti-HCV antibodies who had registered in a specialised viral hepatitis registry since 1994 and who lived in the French departments of Côte-d'Or and Doubs (1 005 817 inhabitants). RESULTS: 1251 of the 1508 recorded cases were studied; 262 were treated. Results of treatment were available in 238 cases, 157 were treated with interferon alone and 81 with interferon + ribavirine. Sustained virological response was observed in 18% of cases after interferon alone and 46.9% after interferon + ribavirine. In multivariate analysis, age under 40 and combined therapy were positively correlated to sustained virological response. Premature treatment discontinuation was associated with a lack of sustained response which was unrelated to gender or liver fibrosis. Fifty seven patients received combined therapy after unsuccessful monotherapy: sustained virological response rates were 33.3% in responders-relapsers and 23.7% in non-responders to initial therapy. CONCLUSIONS: This study showed that sustained response rates were similar in non selected patients from the general population and in highly selected patients from randomised trials. These results emphasize the necessity of increasing the ratio of treated patients which is still too low in general population.

Indications and results of liver transplantation for Echinococcus alveolar infection: an overview.

BACKGROUND: Alveolar echinococcosis (AE) of the liver, caused by the larval stage of the fox tapeworm Echinococcus multilocularis, has the characteristics of a slow-growing liver cancer. It is one of the rare parasitic diseases for which a parasitolytic drug is not yet available, and AE is lethal in the absence of appropriate therapeutic management. Complete surgical resection of the parasite at an early stage of infection provides favourable prospects for cure, but, due to a long clinical latency, many cases are diagnosed at an advanced stage, so that partial liver resection can be performed in only 35% of patients. Benzimidazole (BZM) treatment is given in inoperable cases but these compounds are only parasitostatic, and lifelong therapy is required. During the past 20 years some centres have considered liver transplantation (LT) for the treatment of incurable AE. METHODS: Our review summarizes the results of this experience based on a series of 47 European patients who received transplants between 1985 and 2002, tries to specify the real place of LT for AE, and underlines the measures that could be undertaken in the future to improve the results. RESULTS: Five-year survival was 71%. Five-year survival without recurrence was 58%. Major technical difficulties related either to previous laparotomies or to the loco-regional involvement were observed. The nine early deaths concerned AE patients with a long past-history of symptomatic AE (iterative cholangitis, secondary biliary cirrhosis). Five late deaths were directly related to ongoing AE, located in the brain in three cases, a very rare AE location that was not investigated before LT in these patients. CONCLUSIONS: In general, the pre-LT screening for distant AE metastases appeared insufficient in this series. Heavy immunosuppressive schemes, absence or delayed re-introduction of BZM after LT have clearly played a role in this unfavourable course. This unique experience indicates that, despite major technical difficulties, LT for incurable AE is feasible and could be discussed in very symptomatic cases. Before LT, interventional radiology should be preferred to repeated laparotomies. Pre-LT and post-LT BZM treatment is mandatory. A careful evaluation of possible distant metastases should be done before the decision for LT is made. After LT, the possibility of an ongoing AE must be permanently kept in mind. This could be reduced by lightening the immunosuppressants, carefully following the specific circulating antibodies, and applying a systematic radiological evaluation, not only to the graft but also to the lungs and the brain.

Experience of liver transplantation for incurable alveolar echinococcosis: a 45-case European collaborative report.

BACKGROUND: Alveolar echinococcosis (AE) of the liver is a rare and severe parasitic disease. It behaves like a slow-growing liver cancer, and liver transplantation (LT) has been proposed in advanced cases since 1985. The aim of this retrospective study was to collect all AE transplant cases in Europe, analyze the results, and specify the usefulness of LT for this unusual indication. METHODS: A questionnaire was sent to 83 LT centers from July 1996 to December 1999. RESULTS: Sixty-five centers responded: 45 AE patients (mean age, 45.8 years) underwent an LT procedure at 16 LT centers. The mean interval between diagnosis and LT was 5 years. One patient died during the hepatectomy phase. Five-year survival was 71%. Five-year survival without recurrence was 58%. The nine early deaths were mostly related to bacterial or fungal infections, or both, in patients in bad condition when LT was performed. Six patients had a graft AE reinfection. Five late deaths were related directly to ongoing AE. In the other cases, benzimidazole (BZM) therapy seemed to stabilize AE residues. CONCLUSIONS: This unique experience indicates that LT is feasible for life-threatening AE. Specific management is needed to optimize the results: earlier decision for LT in incurable symptomatic biliary AE, pre- and post-LT BZM therapy, meticulous pre-LT evaluation to identify extrahepatic extension, and an immunosuppressive regimen kept to a minimum.

Risk factors for lymphoproliferative disorders after liver transplantation in adults: an analysis of 480 patients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation that leads to death in more than 50% of cases. The aim of this work was to identify specific risk factors for lymphoproliferative disorders after liver transplantation in adults. METHODS: A total of 480 consecutive patients who underwent transplantation between 1986 and 1997 were studied (323 men, 157 women; mean age: 49.8+/-10.4 years). Demographics, the indication for transplantation, the immunosuppressive regimens, the incidence of rejection episodes, and Epstein-Barr virus infection were analyzed. Univariate and multivariate analysis were used to identify factors predictive of PTLD. RESULTS: Sixteen cases of PTLD (3.3%) occurred at a median of 5.5 (range, 1-39) months after liver transplantation. All 16 cases occurred in patients with evidence of exposure to Epstein-Barr virus before transplantation. In multivariate analysis, the use of antilymphocyte antibodies (P=0.007, relative risk [RR]=4.2, 95% confidence interval [CI]=1.5-11.7), age older than 50 years (P=0.037, RR=3.5, 95% CI=0.95-13.0), liver transplantation for hepatitis C virus cirrhosis (P=0.015, RR=8.7, 95% CI=1-78.3), and liver transplantation for alcoholic cirrhosis (P=0.015, RR=9.6, 95% CI=1.2-77.2) were independently associated with the onset of PTLD. CONCLUSION: Liver transplantation for hepatitis C virus-related and alcoholic cirrhosis and age older than 50 years are three additional risk factors for lymphoproliferative disorder independent of the use of antilymphocyte antibodies. The use of antilymphocyte antibodies after liver transplantation should be avoided in these categories of patients, especially those older than 50 years.

Feasibility of and interest in combined endoscopic ultrasonography and biliary drainage in unexplained acute biliopancreatic disorders.

Combined endoscopic ultrasonography and duodenal bile drainage for microscopic bile examination was prospectively evaluated in patients with unexplained acute biliopancreatic disorders defined as follows: isolated biliary-type pain (group 1), biliary-type pain and elevated transaminases (group 2), or acute pancreatitis (group 3). All patients had prior negative transabdominal ultrasonography. Endoscopic ultrasonography and bile drainage were combined under anesthesia during the same procedure. Combined endoscopic ultrasonography and bile drainage was feasible without any complication in the 48 patients studied. Biliary lithiasis was diagnosed in 20 patients (42%), 5 in group 1 (38%), 7 in group 2 (39%), and 8 in group 3 (47%). Endoscopic ultrasonography and microscopic bile examination were positive respectively in 17 (36%) and in 13 (27%) patients. In conclusion, combined endoscopic ultrasonography and bile drainage for microscopic bile examination is a simple procedure. Biliary lithiasis is diagnosed in a high proportion of patients with unexplained acute biliopancreatic disorders.