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Biomedical subjects

O Farges

Publications and source records attributed to O Farges.

At least 55 records · Page 3Linked to original sources

High preoperative serum alanine transferase levels: effect on the risk of liver resection in Child grade A cirrhotic patients.

Despite careful selection of cirrhotic patients with hepatocellular carcinoma (HCC), liver resection remains associated with a greater risk than in patients without underlying liver disease. In this study we assessed by multivariate analysis parameters associated with in-hospital mortality and morbidity in a selected group of 108 Child-Pugh A cirrhotic patients undergoing liver resection of HCC. The overall incidences of in-hospital deaths and postoperative complications were 8.3% and 48.1%, respectively. By univariate analysis, the preoperative serum alanine transferase (ALT) level (p = 0.001) and intraoperative transfusions (p = 0.01) were significantly associated with in-hospital death; however, only the serum ALT concentration was an independent risk factor. In-hospital mortality rates in patients whose serum ALT was below 2N (twofold the upper limit of the normal value), between 2N and 4N, and more than 4N were 3.9%, 13.0%, and 37.5%, respectively. An ALT level greater than 2N was predominantly observed in patients with a hepatitis C virus infection and significantly associated with histologic features of superimposed active hepatitis. Patients with an ALT level greater than 2N experienced an increased incidence of postoperative ascites (58% versus 32%, p = 0.01), kidney failure (16% versus 0%, p = 0.0003), and upper gastrointestinal bleeding (6.4% versus 0%, p = 0.02). These results indicate that the preoperative ALT level is a reliable predictor of in-hospital mortality and morbidity following liver resection in Child-Pugh A cirrhotic patients. Cirrhotic patients with ALT > 2N should undergo only a limited resection; if a larger resection is required, those patients should be considered for nonsurgical therapy or liver transplantation.

Adult↗

Laparoscopic fenestration in polycystic liver disease.

Sixteen laparoscopic cyst fenestrations for symptomatic adult polycystic liver disease (APLD) were performed in 13 women, including four patients who had had previous attempts at treatment (percutaneous sclerotherapy in two and fenestration via a laparotomy in two). The median number of cysts deroofed was 32 (range 18-58) during the 13 primary procedures. There was no in-hospital death. Postoperative transient ascites occurred in six patients. After operation 11 patients experienced immediate relief of symptoms but during a median follow-up of 26 (range 6-49) months, eight of these patients developed recurrent symptoms. Two patients underwent three repeat laparoscopic fenestrations, at which time perihepatic adhesions were rare and no complication occurred. Because repeat procedures may be performed, laparoscopic fenestration appears to be useful for the treatment of symptomatic APLD. However, it is less effective than fenestration at open surgery or liver resection and should be employed only in patients with predominantly large cysts.

Adult↗

Urinary thromboxane B2 as an indicator of acute rejection in human liver transplantation.

Urinary thromboxane B2 (u-TXB2) was measured and analyzed after a human liver transplantation in 28 patients (30 transplantations) who underwent an orthotopic liver transplantation. Our results showed that the u-TXB2 levels exceeded 3.0 micrograms/mmol creatinine in only 2 of the 13 cases that had a favorable postoperative course. In 10 of the 11 episodes of acute rejection, the u-TXB2 levels exceeded 3.0 micrograms/mmol creatinine. In 6 episodes of acute rejection, the TXB2 levels were more than 5.0. In 4 out of 6 episodes of infection unassociated with rejection, the u-TXB2 values were between 3.0 and 4.9 micrograms/mmol creatinine. In 2 episodes of liver necrosis the TXB2 value reached 5.3 in one and 0.9 in the other. In conclusion, the u-TXB2 level was observed to be elevated in cases of acute rejection, infection, or necrosis. The diagnosis of acute rejection on the basis of u-TXB2 showed a sensitivity of 58.8%, a specificity of 93.3%, and an accuracy of 75.0% for a threshold level of 3.0 micrograms/mmol creatinine, and a sensitivity of 85.7%, a specificity of 79.2%, and an accuracy of 80.6% for a threshold level of TXB2 of 5.0 micrograms/mmol creatinine. These results indicate that the serial determination of u-TXB2 is a useful diagnostic means for predicting acute rejection after liver transplantation.

Adolescent↗

Incidence of rejection and infection after liver transplantation as a function of the primary disease: possible influence of alcohol and polyclonal immunoglobulins.

A retrospective analysis was undertaken to determine if the incidence, timing, and severity of acute and chronic rejection were influenced by the primary disease necessitating transplantation. Of the 875 liver transplantations performed between 1984 and 1992, 768 were primary transplantations and 107 were retransplantations. Among the former, 330 patients that were liver transplant recipients for a chronic liver disease without cancer in the native liver received an ABO-compatible and cross-match-negative graft and were given a cyclosporine- or tacrolimus-based immunosuppression. These included primary biliary cirrhosis (PBC, 66 patients), primary sclerosing cholangitis (PSC, 23 patients), alcoholic cirrhosis (ALC, 21 patients), autoimmune cirrhosis (AIC, 17 patients), hepatitis B virus-induced cirrhosis (HBV-C, 116 patients) and hepatitis C virus-induced cirrhosis (HCV-C, 87 patients). The incidence of acute (48% +/- 3% [SE] at 1 year) and chronic rejection (10% +/- 2% at 3 years) was comparable in patients who have undergone transplantation for PBC, PSC, AIC, and HCV-C. However, the incidence of acute (but not chronic) rejection was significantly lower in patients who have undergone transplantation for ALC (29% at 1 year). This reduced incidence of acute rejection was associated with an increased incidence of bacterial infections. In patients who have undergone transplantation for HBV-C (the majority of whom had received long-term anti-hepatitis B surface antigen [HBs] immunoglobulins), the incidence of both acute (21% at 1 year) and chronic rejection (0% at 3 years) was significantly lower, whereas the incidence of septic complications was comparable with that in the other groups. The incidence of acute rejection in patients who have undergone transplantation for nonviral disease receiving polyclonal human anti-cytomegalovirus (CMV) immunoglobulins was also significantly lower than that of patients who did not receive the immunoglobulins (19% vs. 48% at 3 months; P = .01), and this was identical to that of patients who have undergone transplantation for viral disease receiving polyclonal human anti-HBs immunoglobulins (19% at 3 months). These results show that the risk of rejection is unequal among patients, being lower in patients who have undergone transplantation for ALC (probably as a result of a state of nonspecific hyporesponsiveness) and in patients who have undergone transplantation for HBV-C (possibly as a result of long-term administration of polyclonal human immunoglobulins).

Adult↗

Anti-donor antibody class switching after liver transplantation.

The humoral immune response directed against donor antigens was monitored by flow cytometry in 17 liver transplant patients using donor leukocytes as targets. Overall, donor-specific antibodies developed in 15 patients; these included all 9 patients who had experienced a biopsy-proven episode of acute rejection and 6 out of 8 patients who had not had an acute episode of rejection. The isotypes of the donor-specific antibodies in the 9 patients who had experienced an early episode of acute rejection were IgG in 8 patients, IgE in 8 patients, and IgA in 6 patients; all 9 patients had IgE and/or IgA antibodies. In the 6 patients who showed no evidence of acute clinical rejection but nevertheless developed donor-specific antibodies, the isotype was IgM associated in 5 of them, with an immunoglobulin class switching to the IgG isotype; none of these patients had antibodies of the IgA or IgE isotype. These results indicate that the lack of rejection of a liver allograft does not necessarily result from a lack of immune response against donor antigens. Rather, the distinct pattern of (cytokine dependent) immunoglobulin class switching suggests that the lack of liver graft rejection may be the result of an immune activation pathway distinct from that resulting in graft rejection.

Adult↗

The use of ABO-incompatible grafts in liver transplantation: a life-saving procedure in highly selected patients.

The aim of this study was to assess the long term results of 43 ABO-incompatible liver transplantations performed in 40 patients. The 5-year patient and graft survival rates were 50 and 20%, respectively. In the group of patients transplanted in emergency for fulminant or subfulminant liver failure, ABO incompatibility had no significant impact on patient survival (P = 0.09). Graft survival, however, was significantly impaired (P = 0.0002) through a greater incidence of hyperacute rejection (20%), vascular thrombosis, and biliary injury (56%). Increasing the magnitude of immunosuppression and postoperatively reducing the titer of anti A/B antibodies by plasmapheresis had little influence on the incidence of these complications and were associated with a greater incidence of septic complications. These results indicate that the use of ABO-incompatible liver grafts is a life-saving procedure in patients with life-threatening acute liver failure, but at a high price. Justification for accepting or not accepting an ABO-incompatible graft in these emergency situations depends on the personal choice in giving priority to saving the patient in an acute life-threatening condition or to giving the graft the best chance of success. To avoid this difficult choice, efforts should aim at expanding the pool of grafts available in emergency, at developing artificial support devices that could allow to safely delay transplantation, or at more efficiently controlling the humoral response.

ABO Blood-Group System↗

Expression of serum albumin and of alphafetoprotein in murine normal and neoplastic primitive embryonic structures.

Alphafetoprotein (AFP), a major serum protein synthesized during the embryo-fetal and postnatal period (in the yolk sac, then in the liver), is also an oncoprotein. The intracellular presence of AFP and of serum albumin (SA) in normal and neoplastic neural crest and neural tube derivatives was previously demonstrated. In this work we have studied the comparative expression of AFP and SA in primitive neuroectoblastic structures of mouse embryos (6 and 7 days "post coitum") and mouse teratocarcinomas (derived from the PCC4 cell line). Using immunofluorescence technique, antibodies to SA gave a positive reaction in embryos of 7 days, while AFP was not detected during this period. By mRNA in situ hybridization, SA mRNA gave a strong signal in both 6 and 7 day embryos, whereas AFP mRNA gave a weak signal only in 7-day embryos. The distribution of SA and AFP and their mRNAs was investigated in primitive neuroectoblastic structures of the teratocarcinomas by in situ hybridization and immunostaining. Only SA protein was detectable by immunostaining. SA mRNA gave a strong signal in differentiating structures as well as in undifferentiated cell clusters. AFP mRNA was observed only in differentiating structure. Dot-blot hybridization indicated that the level of SA transcripts was at least 6-fold higher than that of AFP transcripts in the teratocarcinomas investigated. In teratocarcinoma-bearing mice injected intraperitoneally with 125I-radiolabeled SA and AFP, significant accumulations of both SA and AFP were demonstrated in the tumors, SA being about 3-fold higher than that of AFP after normalization to quantity of uptake in liver. External in vivo photoscanning confirmed this relationship of accumulated radiolabeled proteins. The last observation could be useful in vivo for diagnosis of teratocarcinoma. We conclude that the expression of SA relative to AFP and the external cellular uptake of SA relative to AFP are similar in normal embryonic developing tissues and in the corresponding morphologically neoplastic tissues of the teratocarcinomas. The same SA:AFP relationship constitutes an oncofetal marker of primitive neuroectoblastic structures.

Animals↗

Kinetics of anti-M2 antibodies after liver transplantation for primary biliary cirrhosis.

BACKGROUND/AIMS: Orthotopic liver transplantation is currently considered as the treatment of choice for primary biliary cirrhosis in the terminal stage and, as for other autoimmune liver disease, the risk of recurrence of the disease within the graft has been raised. There is, however, some discrepancy about the risk of recurrence based on pathological analysis. In addition, pathological recurrence of primary biliary cirrhosis within the graft is not always associated with a rise in the serological markers of the disease. In order to clarify this situation, we have monitored antimitochondrial antibodies before and after transplantation. METHODS: Antimitochondrial antibodies were detected by indirect immunofluorescence (variation in antibody titers) and the antimitochondrial antibodies-2 by western blotting (variation in the number of peptides recognized in 16 primary biliary cirrhosis patients followed for at least 4 years after transplantation. RESULTS: Antimitochondrial antibody titers had normalized 1 year after transplantation in seven patients, declined in seven others and remained unchanged in two. Over the 4 years of follow up, four patients demonstrated a subsequent increase in antimitochondrial antibody titers. Western blot analysis demonstrated the loss of one or more bands in seven patients during the first operative year after transplantation and in three other patients thereafter; in six patients the western blotting profile remained identical to that obtained before transplantation. The important changes generally occurred during the first year post-transplantation, without significant changes thereafter, except for three patients who demonstrated a secondary reappearance of the initially lost band. Disappearance of all bands was never observed. There was no concordance between the normalization of antimitochondrial antibody titers (indirect immunofluorescence) and the reduction in the number of peptides recognized (western blotting). Serum bilirubin and alkaline phosphatase levels had normalized by 1 year after transplantation, and remained normal thereafter. Routine liver biopsies performed on a yearly basis did not disclose any pattern suggestive of primary biliary cirrhosis recurrence. CONCLUSIONS: Antimitochondrial antibody titers decreased in primary biliary cirrhosis patients after liver transplantation, although antimitochondrial antibodies-2 never disappeared as assessed by western blotting. In the present study these features were not associated with biochemical or histological (correction of histoclogical) evidence of primary biliary cirrhosis recurrence.

Adult↗

Primary sclerosing cholangitis: liver transplantation or biliary surgery.

BACKGROUND: Little information is available on the indications for, and the efficacy and timing of, liver transplantation in patients with primary sclerosing cholangitis (PSC). This issue is particularly relevant because prolonged survival has been reported in patients who do not undergo transplantation. METHODS: Long-term results of therapeutic interventions including liver transplantation was assessed in a representative series of 51 patients. Patient survival was compared with that expected from prognostic models. RESULTS: Actuarial symptom-free survival rate in patients treated by nontransplantation biliary surgery (n = 23) was 35% at 10 years. Actuarial survival rate from onset of PSC (56% at 10 years) was identical to that expected from the prognostic model. Actuarial patient (n = 28) survival rate 5 years after transplantation was greater than that expected from prognostic models (89% versus 31%; p < 0.001). Previous abdominal surgery was associated with an increased in-hospital mortality rate (p < 0.05). Cumulative actuarial incidence of cancer 5 and 10 years after the onset of PSC was 13% and 31%, respectively. CONCLUSIONS: Liver transplantation improves the prognosis of patients with PSC. Failure to identify patients who will benefit from nontransplantation therapeutic interventions or in whom a cancer will develop, and the risk associated with previous abdominal surgery, suggest that liver transplantation should be indicated early after onset of symptoms.

Adult↗

Sclerosing cholangitis following human orthotopic liver transplantation.

Sclerosing cholangitis defined by cholangiographic criteria may occur after orthotopic liver transplantation. In this retrospective study, we analyzed failed grafts and antecedent serial biopsies of 24 patients who developed this type of nonanastomotic biliary strictures. Sclerosing cholangitis was histologically diagnosed if there was a combination of periductal fibrosis and features of large bile duct obstruction. The condition was observed in all but one available failed allografts. This later showed ischemic-type lesions without periductal fibrosis. Liver biopsy specimens were nondiagnostic relative to sclerosing cholangitis, although 85% of the patients had evidence of large bile duct obstruction. Numerous associated factors may explain the pathogenesis of secondary sclerosing cholangitis: an immunologically related etiologic factor (10 recipients of ABO-incompatible allografts) and compromised arterial blood flow that likely resulted from hepatic artery thrombosis (12 patients), focal arterial fibrointimal hyperplasia (three patients), chronic ductopenic arteriopathic rejection (three patients) and/or preservation-related ischemia (four patients). Sclerosing cholangitis may be a significant cause of graft failure that often has misleading biopsy manifestations. From a practical standpoint, cholestasis with evidence of large bile duct obstruction warrants cholangiographic assessment of the biliary tree.

Adolescent↗