Solange Bresson-Hadni

Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.

The actual impact of transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were evaluated for LT. Among these 479 patients, this case‐control study included 100 patients who received transarterial chemoembolization before LT (TACE group) and 100 control patients who did not receive chemoembolization (no‐TACE group). Patients and controls were matched for the pre‐LT tumor characteristics, the period of transplantation, the time spent on the waiting list, and pre‐ and posttransplantation treatments. Kaplan‐Meier estimates were calculated 5 years after LT and were compared with the log‐rank test. The mean waiting time before LT was 4.2 ± 3.2 months in the TACE group and 4.3 ± 4.4 months in the no‐TACE group. The median number of TACE procedures was 1 (range: 1‐12). Demographic data, median alpha‐fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively), and pre‐ and post‐LT morphologic characteristics of the tumors did not differ in the TACE and no‐TACE groups. Overall 5‐year survival was 59.4% with TACE and 59.3% without TACE (ns). Survival rates did not differ significantly between the two groups with respect to the time on the waiting list, the tumor diameter, or the type of TACE (selective or nonselective). In the TACE group, 30 patients had tumor necrosis ≥80% on the liver explant with a 5‐year survival rate of 63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion, with a mean waiting period of 4.2 months and 1 TACE procedure, pre‐LT TACE does not influence post‐LT overall survival and disease‐free survival. (Liver Transpl 2005;11:767–775.)

Transglutaminase-mediated cross-linking is involved in the stabilization of extracellular matrix in human liver fibrosis

BACKGROUND/AIMS Lysyl oxidase-mediated cross-linking contributes to the stabilization of collagen in liver fibrosis. We have investigated transglutaminase-mediated cross-linking, to determine if it participates in the stabilization of extracellular matrix in human liver fibrosis. METHODS Transglutaminase activity was assessed in vitro by incorporation of biotinylated amine into liver proteins. The product of the transglutaminase-catalyzed cross-linking reaction, Nepsilon(gamma-glutamyl)lysine, and the extracellular proteins cross-linked by it, were localized by immunohistochemistry in fibrotic livers. The cross-linked complexes were extracted from liver tissue, immunopurified and characterized by Western blot. RESULTS Transglutaminase, detected by immunohistochemistry, Western blot and by enzymatic activity, was found in higher amounts in fibrotic than in normal liver. The Nepsilon(gamma-glutamyl)lysine cross-link, undetectable in normal liver, was present extracellularly in fibrotic liver, where it was co-distributed with osteonectin, mostly in inflammatory areas submitted to an intense remodeling. Cross-linking of osteonectin by transglutaminase was confirmed by Western blot. In parasitic fibrosis transglutaminase also originates from the parasite. CONCLUSIONS Transglutaminase-mediated cross-linking occurs in liver extracellular matrix during the early, inflammatory, stage of liver fibrosis, whereas cross-linking by pyridinoline occurs mostly later in the fibrotic process. This could lead to the development of new anti-fibrotic treatments targeted to a specific stage of fibrosis.

Reactivation of a latent precore mutant hepatitis B virus related chronic hepatitis during infliximab treatment for severe spondyloarthropathy

We report a case of hepatitis B virus (HBV) reactivation following the use of anti-tumour necrosis factor α (TNFα) antibodies that illustrates the need for careful viral monitoring and pre-emptive antiviral treatment in such patients. A 35 year old white woman presented with a history of chronic hepatitis B without an increase in serum alanine aminotransferase (ALT) or detectable HBV DNA by a hybridisation technique since its diagnosis (in 1993); she was thus considered to be an asymptomatic HBV carrier. Her serological status was as follows: hepatitis B surface antigen positive, hepatitis B e antigen negative, hepatitis B e antibody positive, suggesting HBV precore mutant. Her rheumatological history began in September 2001 with oligoarthritis, inflammatory low back pain, limitation of motion, and anterior chest wall involvement. Symptoms improved incompletely with non-steroidal anti-inflammatory drugs. Biological inflammation (erythrocyte sedimentation rate 62 mm/1st h, C reactive protein 53 mg/l), positive HLA-B27 …

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

Objectives Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20‐year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. Design One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. Methods Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut‐off year because of the numerous changes that occurred in the diagnosis, follow‐up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. Results The results of patient follow‐up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100 000 persons in period A whereas it reached 6.6 per 100 000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty‐nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non‐operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two‐thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. Conclusions Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease. Eur J Gastroenterol Hepatol 12:327‐336

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 of complications after abdominal paracentesis in cirrhotic patients: a prospective study.

BACKGROUND & AIMS Complications and technical problems of paracentesis in cirrhotic patients are infrequent. However, the severity and the incidence of these events and their risk factors have not been assessed prospectively. METHODS Cirrhotic patients (n = 171) undergoing paracentesis were included. Of the 515 paracenteses, 8.8% were diagnostic, and 91.2% were therapeutic. Technical features, demographic data, and adverse events during a period of 72 hours after the procedure were examined. RESULTS Major complications occurred in 1.6% of procedures and included 5 bleedings and 3 infections, resulting in death in 2 cases. Major complications were associated with therapeutic but not diagnostic procedures and tended to be more prevalent in patients with low platelet count (<50 10(9)/L), Child-Pugh stage C, and in alcoholic cirrhosis patients. Technical problems occurred in 5.6%. The most frequent complication was a leak of ascites at the puncture site (5.0%), and in 89.5% there were no complications. CONCLUSIONS The safety of paracentesis in cirrhotic patients might be decreased if risk factors, which depend on the characteristics of the patient and of the procedure itself, are present.

Vascular involvement of the liver in Turner's syndrome

Unexplained liver test abnormalities are frequent in patients with Turners syndrome. This cohort study was performed to clarify the histopathologic features, causes, and long‐term outcome of liver involvement in these patients. Thirty patients with persistently abnormal liver test results were followed‐up for 8.8 ± 5.2 years. Liver specimens were available in 27 patients. Marked architectural changes were present in 10 patients, including nodular regenerative hyperplasia in six, multiple focal nodular hyperplasia in two, and cirrhosis in two patients. These changes frequently were associated with obliterative portal venopathy lesions and with aortic malformations. There was mild to moderate portal fibrosis in 15 of the 17 other patients, inflammatory infiltrates in nine patients, and nonalcoholic fatty liver disease in 11 patients. Bile duct alterations resembling small duct sclerosing cholangitis were observed in 21 patients (with or without architectural changes). There was no viral, alcoholic, autoimmune, or drug‐induced liver damage. Portal hypertension was observed in four patients with marked architectural changes, including three in whom refractory ascites or recurrent variceal bleeding developed, one of whom underwent transplantation. None of the patients without marked architectural changes experienced progressive or decompensated liver disease. There was no evidence of liver toxicity from estrogen replacement therapy. In conclusion, the main causes of liver involvement in Turners syndrome are vascular disorders, probably of a congenital origin, and nonalcoholic fatty liver disease. In patients with vascular disorders, severe liver disease requiring liver transplantation may develop. Estrogen therapy does not appear to be pathogenically implicated. (HEPATOLOGY 2004;39:239–247.)

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

BackgroundAlveolar 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.MethodsOur 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.ResultsFive-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.ConclusionsIn 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.

Clinical features and evolution of alveolar echinococcosis in France from 1982 to 2007: Results of a survey in 387 patients

BACKGROUND & AIMS Alveolar echinococcosis (AE) is a rare disease in humans, caused by the larval stage of the fox tapeworm Echinococcus multilocularis. METHODS We present here 387 detailed AE cases diagnosed in France from 1982 to 2007 actively identified by a retrospective survey performed in 1997-1998 and prospectively thereafter. RESULTS Male:female ratio was 1.03 and mean age 57.8 years at time of diagnosis. Among the 362 complete files (including 347 non dead-out and 15 dead-out lesions), 73% of the patients were symptomatic at first admittance. Among them, 83% presented with clinical patterns evocative either of a digestive or a hepatic disorder. Other symptomatic patients presented with erratic clinical pictures, generally due to metastasis or extra-hepatic location of the parasite. Except for a few patients with particularly severe AE who died shortly after the diagnosis, most patients were treated using benzimidazoles. Their mortality tends to merge with that of the general French population, matched by sex, age, and calendar year. This study also highlights an unexpectedly high frequency of blood-tied family cases (13% of patients submitted to a specific questionnaire). CONCLUSIONS Even though the broad set of clinical features provoked by E. multilocularis makes AE a potential diagnostic trap for many physicians, our study revealed an improvement of its prognosis. However, as shown by our findings about the frequency of family cases, there is still a need for studies aimed at better describing this uncommon parasitic disease.

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.