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D Houssin

Publications and source records attributed to D Houssin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Is acute rejection deleterious to long-term liver allograft function?

BACKGROUND/AIMS: The decreasing incidence of chronic rejection after liver transplantation emphasizes the need for an alternative end-point to assess the long-term consequences of acute rejection. The purpose of this study was to determine the effects of resolved episodes of acute rejection on late liver allograft function. METHODS: Parameters of hepatic function (liver biochemistry, indocyanine green and sulfobromophthalein clearances, histology) were analyzed in 170 consecutive adult recipients, who were followed prospectively on the basis of repeat annual work-up. Mean follow-up was 3.7+/-0.2 years. RESULTS: The rates of acute and chronic rejection were 51% and 4.1%, respectively. At the last follow-up, there was no significant difference in graft function between patients with a single episode of acute rejection (n=56) and those without rejection (n=84). Among patients treated for a single episode of acute rejection, late hepatic function was not influenced by the severity of acute rejection and the response to corticosteroids. In contrast, patients with recurrent acute rejection (n=30) had significant impairment of liver function tests (aspartate aminotransferase, p<0.05; alanine aminotransferase, p<0.01; alkaline phosphatase, p<0.01; gamma-glutamyl transpeptidase, p<0.001), lower dye clearances (indocyanine green, p<0.01; sulfobromophthalein, p<0.01) and more severe histologic damage (p<0.001). CONCLUSIONS: Single episodes of acute rejection do not impair the long-term hepatic function, whereas recurrent episodes leave sequellar damage to the liver allograft. These results provide a rationale for converting patients with rejection to a heavier immunosuppressive regimen, while leaving nearly half the recipients on a lifelong light immunosuppressive regimen.

Adolescent↗
PubMed1998

Extrahepatic portal hypertension following liver transplantation: a rare but challenging problem.

This study reports our experience of 8 cases of extrahepatic portal hypertension after 273 orthotopic liver transplantations in 244 adult patients over a 10-year period. The main clinical feature was ascites, and the life-threatening complication was variceal bleeding. Extrahepatic portal hypertension was caused by portal vein stenosis in 6 patients, and left-sided portal hypertension in 2 patients after inadventent ligation of portal venous tributaries or portasystemic shunts. All patients with portal vein stenosis had complete relief of portal hypertension after percutaneous transhepatic venoplasty (n = 4) or surgical reconstruction (n = 2), after a median follow-up of 33 (range: 6-62) months. Of the 2 patients with left-sided portal hypertension, one died after splenectomy and one rebled 6 months after left colectomy. This study suggests that extrahepatic portal hypertension is a series complication after liver transplantation that could be prevented by meticulous portal anastomosis and closure of portal tributaries or portasystemic shunts to improve the portal venous flow. However, any ligation has to be performed under ultrasound guidance to avoid inadventent venous ligations.

Adult↗
PubMed1998

[Liver resection in a state of normothermic ischemia].

Thirty-three patients undergoing liver resection in a state of normothermic ischemia are described: portal clamping is done in 25 cases at mean duration 41 +/- 8 min, and vascular exclusion of liver--10 cases at mean duration 44 +/- 12 min. This is a procedure accounting for a substantial reduction of intraoperative hemorrhages. In 17 patients hemotransfusion proves unnecessary, while in the remainder the amount of blood transfused averaged 1500 +/- 950 ml.

Adult↗
PubMed1998

Are hepatomas a good target for suicide gene therapy? An experimental study in rats using retroviral-mediated transfer of thymidine kinase gene.

BACKGROUND: Suicide gene transfer into tumor cells has been proposed for the treatment of various tumors. The most common suicide gene is coded for the herpes simplex type I thymidine kinase (HSV1-TK), which converts nontoxic nucleoside analogs such as ganciclovir into toxic triphosphated compounds. This study evaluated the potential of this treatment for gene therapy of liver tumors. METHODS: The sensitivity of different colon carcinoma and hepatoma cell lines to infection by recombinant retroviruses was evaluated. Next, HSV1-TK-expressing derivatives of these cells were generated to analyze their sensitivity to ganciclovir. Finally, these cells were used to generate experimental hepatomas in rats after injection under the liver capsule, and the efficacy and safety of a ganciclovir treatment on tumor growth and survival were evaluated. RESULTS: All the different cell lines analyzed were sensitive to retroviral-mediated gene transfer, although the susceptibility of individual cell lines to this transfer varied significantly. HSV1-TK derivatives were about 1000-fold more sensitive to the toxic effects of ganciclovir than parental cells. Tumors with HSV1-TK expressing MCA-RH8994 hepatoma cells were then generated. Intraperitoneal injection of 75 mg/kg ganciclovir twice daily for 5 days dramatically reduced the size of HSV1-TK-positive tumors compared with tumor size in untreated control rats (0.4 mm3 versus 65 mm3, p < 0.02). A long-term study demonstrated that this reduction of tumor volume was associated with a significant increase in survival (p < 0.01). Pathologic examination 26 days after the end of ganciclovir injections showed that complete tumor regression was observed in two of five rats. Most important, there was no toxicity associated with these tumors. CONCLUSIONS: In a clinical perspective the good tolerance to treatment and the significant clinical effect observed were encouraging. Gene transfer methods should be established to allow efficient targeting of the tumor cells in vivo.

3T3 Cells↗
PubMed1997

Common bile duct stenosis caused by chronic pancreatitis after liver transplantation for alcoholic cirrhosis.

BACKGROUND: The prevalence of chronic pancreatitis in patients with alcoholic cirrhosis ranges from 7% to 11% and is not considered a contraindication for liver transplantation. METHODS: Among 59 liver transplant recipients grafted for alcoholic cirrhosis, we report two observations of common bile duct stenosis due to chronic pancreatitis. RESULTS: In both cases, pretransplant work-up disclosed no clinical or radiological evidence of chronic pancreatitis. The diagnosis of common bile duct stricture was made 6 and 60 months after liver transplantation. One patient was reoperated upon, and his choledochocholedochostomy was converted into a Rouxen-Y choledochojejunostomy. The second patient experienced metastatic laryngeal carcinoma and died before reoperation. CONCLUSIONS: These observations suggest that common bile duct stricture caused by chronic pancreatitis may occur after liver transplantation for alcoholic cirrhosis, even after a long-standing history of abstinence.

Adult↗
PubMed1997

A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor.

Antitumor gene therapy using herpes simplex type 1 thymidine kinase (TKh) and ganciclovir (GCV) treatment has revealed an important intratumoral bystander effect. A whole tumor can be eliminated when only a fraction of its tumor cells express TKh. We now report that the bystander effect not only acts within a tumor, but also between distant tumors. One TKh+ tumor was generated simultaneously with one or multiple TKh- tumors in different rat liver lobes such that there was no contact between the resulting tumors. Both the TKh+ and the TKh- tumors regressed after GCV treatment and showed infiltration with macrophages and T lymphocytes. This distant bystander effect, which is likely immune mediated, should be of major importance for gene therapy of disseminated tumors.

3T3 Cells↗
PubMed1997

Calcitonin mRNA is produced in liver by two different splicing pathways.

Calcitonin, the hypocalcemic hypophosphatemic hormone is produced in the thyroid by the C-cells. We recently detected the presence of calcitonin and its messenger in hepatic tissue in vivo and in vitro. The calcitonin precursor is composed of the N-terminal peptide, calcitonin and a carboxyterminal peptide. We previously reported that in normal human thyroid and in medullary thyroid carcinoma a second calcitonin messenger is expressed in low quantities. This mRNA differs in its 3' region from the first one. It also codes for the N-terminal peptide, calcitonin and a carboxyterminal peptide which differs by the last eight amino acids from the first. We report here that both calcitonin mRNAs are expressed in normal or tumoral liver. Direct estimation, by a specific immunoassay, of the levels of carboxyterminal peptide II, the specific peptide coded for by calcitonin mRNA II, confirmed that this peptide is synthesized in human liver.

Alternative Splicing↗
PubMed1997

Rationale and technical constraints of a tertiary liver transplantation.

Because of the current shortage of donor organs, the routine performance of tertiary liver transplantation (LT) may be questioned. In this study, the indications of tertiary LT are discussed, paying particular attention to intraoperative technique. Of 501 LTs performed from 1986 to 1995, eight (1.6%) were tertiary LTs. Three patients underwent an emergent third LT because of associated hepatic artery and portal vein thromboses (n = 2) or hyperacute rejection (n = 1). Five patients had an elective third LT for ischemic cholangitis (n = 4) or chronic rejection (n = 1). The 3 patients who underwent retransplantation emergently died early from multiple-organ failure. Because of previous surgery and subsequent technical difficulties, the third LT in the remaining 5 patients required unroutine surgical procedures including the following: intrapericardial control of the suprahepatic vena cava (n = 1), "en bloc" clamping of both the infrahepatic vena cava and the hepatic pedicle (n = 1), arterial reconstruction onto the aorta via an aortoiliac conduit (n = 5), and aortic resection with aortoaortic prosthetic reconstruction (n = 1). Of these 5 patients, 4 required reoperation because of bowel perforation (n = 5) or intraperitoneal bleeding (n = 1). The 5 patients (62%) who were regrafted electively are alive and well after a median follow-up of 45 months. A third LT can be reasonably offered to selected young recipients if performed electively. Tertiary LT may require unroutine surgical procedures and may lead to severe morbidity.

Adult↗
PubMed1997

Endothelin-1 induces liver vasoconstriction through both ETA and ETB receptors.

BACKGROUND/AIMS: We investigated which endothelin receptors mediate the vasoconstrictive effects of endothelin-1 on liver circulation. METHODS: An isolated perfused rat liver model in recirculation was used. RESULTS: The perfusion of 10(-10) M endothelin-1 had no significant influence on the liver flow, whereas 10(-9) M endothelin-1 induced significant vasoconstriction, with flow dropping from 3.20 +/- 0.34 to 1.48 +/- 0.28 ml. min-1.g-1 liver tissue (p < 0.01 vs controls). The liver flow was interrupted following the perfusion of 10(-8) M endothelin-1. Sarafatoxin C and BQ 3020, two agonists of ETB receptor, had vasoconstrictive effects in this model. Sarafatoxin C decreased the liver flow in a dose-dependent manner, from 3.32 +/- 0.21 to 2.18 +/- 0.20, 1.60 +/- 0.09, and 1.01 +/- 0.06 ml.min-1. g-1, respectively, with 10(-9) M, 10(-8) M, and 10(-7) M. While BQ 123, an antagonist of ETA receptor, or BQ 788, an antagonist of ETB receptor, partially reversed the effect of 10(-9) M endothelin-1, the simultaneous administration of BQ 123 and BQ 788 completely reversed these effects. CONCLUSIONS: These results indicate that the vasoconstrictive effects of endothelin-1 on the liver circulation are mediated through both ETA and ETB receptors.

Animals↗
PubMed1997

Protein-losing enteropathy secondary to hepatic venous outflow obstruction after liver transplantation.

A 42-year-old man with a history of repeated abdominal surgery and lymph node tuberculosis underwent orthotopic liver transplantation for primary sclerosing cholangitis. Two years after transplantation, this patient developed a severe protein-losing enteropathy with no evidence of cardiac disease or lymphoproliferative disorder. Imaging work-up revealed hemodynamically significant stenosis of the supra-hepatic caval anastomosis, which was treated by percutaneous balloon angioplasty. All clinical and biochemical disorders resolved within 1 month after percutaneous dilatation, but relapsed simultaneously with recurrent anastomotic stenosis 15 months later. Repeat caval angioplasty resulted in rapid recovery, which strongly suggests that hepatic venous outflow obstruction was responsible for the protein-losing enteropathy in this patient.

Adult↗
PubMed1997

NO-mediated vasodilation in the rat liver. Role of hepatocytes and liver endothelial cells.

BACKGROUND/AIMS: Nitric oxide (NO) is a potent vasodilator. We investigated the mechanisms responsible for this effect in the liver. METHODS: Isolated perfused rat liver and cultures of endothelial sinusoidal cells and hepatocytes were used. RESULTS: L-arginine (10(-3) M) and NO donor Sin-1 (10(-5) M) respectively increased the liver flow by 52% (p<0.01) and 93% (p<0.01) vs controls. The NO synthase inhibitor Nw-nitro-L-arginine (10(-3) M) and the guanylate cyclase inhibitor methylene blue (10(-5) M) respectively decreased the basal liver flow by 26% and 16% (p<0.05) and inhibited the vasodilating effects of L-arginine. L-arginine (10(-3) M) increased nitrite concentration in hepatocyte culture (77.25+/-7.40 micromol x l(-1) vs 14.70+/-3.55 micromol x l(-1) in controls; p<0.01) and in liver endothelial cell culture (0.36+/-0.09 micromol x l(-1) vs 0.12+/-0.05 micromol x l(-1) in controls; p<0.05). Nw-nitro-L-arginine inhibited the basal production and abolished the L-arginine-induced production of nitrites both in hepatocyte and in liver endothelial cell cultures. The concentration of nitrites in the hepatocyte supernatant rose from 14.70+/-3.55 micromol x l(-1) to 150.50+/-45.55 micromol x l(-1) in the presence of a combination of interleukin-1beta, TNF alpha and interferon gamma. CONCLUSIONS: Under basal conditions, NO regulates the vascular tone of liver circulation. Both liver endothelial cells and hepatocytes can be implicated. NO production by hepatocytes may increase during inflammation.

Animals↗
PubMed1996

Comparison between aortic and sinusoidal liver endothelial cells as targets of hyperacute xenogeneic rejection in the pig to human combination.

Endothelial cells of aortic origin are usually used in vitro as targets of hyperacute xenogeneic rejection, although endothelial cells from organs may have different properties. The sensitivities of aortic and liver endothelial cells to hyperacute xenogeneic rejection were compared in the pig to human combination. Sinusoidal liver endothelial cells were isolated and purified by collagenase perfusion of pig livers, sedimentation on a percoll gradient and selective adherence. Purity and viability of isolated liver endothelial cells after adherence were 85+/-6% and >95%, respectively. Endothelial cells from pig aortae (purity and viability >95%) were isolated by scraping. Immunoblotting analysis of xenoantigens on liver and aortic endothelial cell membranes preparations showed identical patterns. The strongest bands revealed by human IgM were located between 110 and 135 kD, while human IgG detected two major bands at 115 and 75kD. The membrane expression of xenoantigens recognized by human sera, analyzed by flow cytometry, was significantly lower on liver than on aortic endothelial cells (IgM: P=0.0006; IgG: P=0.0009). However, the complement-dependent cytotoxic activity of human sera was the same whether liver (54.5+/-1.4%) or aortic endothelial cells (50.0+/-4.2%) were used as targets. Taken together, those results allow the use of aortic instead of sinusoidal liver endothelial cells in the characterization of pig antigens recognized by human natural antibodies.

Acute Disease↗