alpha-Interferon-induced rejection of a hepatitis C virus-infected liver allograft tolerated with a low dosage immunosuppressive regimen.
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Azathioprine↗
Biomedical subjects
J Belghiti
Publications and source records attributed to J Belghiti.
Antituberculous therapy and acute liver failure.
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Antitubercular Agents↗
Transplantation for fulminant and subfulminant hepatic failure with preservation of portal and caval flow.
This article describes experience with preservation of portal and caval flow during orthotopic liver transplantation (OLT) for fulminant or subfulminant hepatic failure (FSHF) as an alternative to venous bypass. As a modification of the standard procedure, hepatectomy and graft implantation were performed with preservation of caval patency in combination with a temporary portocaval shunt. From July 1991 to March 1994, 25 consecutive patients with FSHF underwent OLT with preservation of portal and caval flow. All patients had severe confusion (n = 9) or coma (n = 16) with a mean(s.d.) clotting factor V of 13(5) per cent and a mean(s.d.) serum bilirubin level of 408(151) mumol/l. During the anhepatic phase, haemodynamic data showed a preservation of cardiac filling pressure, mean arterial pressure, and renal perfusion pressure, while the mean(s.d.) urine flow was maintained at 182(120) ml/h. Venous bypass was not required. There were three (12 per cent) deaths after the operation, and all survivors made a full neurological recovery. Normal postoperative creatinine values allowed the early use of baseline immunosuppression. The authors conclude that, in patients with FSHF, successful liver transplantation can be achieved with this technical procedure.
Adult↗
Preservation of renal perfusion and postoperative renal function by side-to-side cavo-caval anastomosis in liver transplant recipients.
Postoperative renal failure is common after liver transplantation (LT). The aim of this study was to investigate peroperative renal perfusion and postoperative renal function in 12 patients who underwent LT with side-to-side cavo-caval anastomosis (SSCCA). Three phases were considered during the procedure: hepatectomy, the anhepatic phase, and the postreperfusion phase (phases 1, 2, and 3, respectively). Mean arterial pressure, IVC pressure, and renal perfusion pressure were significantly higher during phase 2 than during phases 1 and 3. Cardiac index and pulmonary capillary wedge pressure did not differ significantly during the three phases. Creatinine clearance did not significantly decrease postoperatively. We conclude that SSCCA is associated with both the preservation of renal perfusion pressure during the entire procedure and the preservation of postoperative creatinine clearance. It is, moreover, a technique that results in a low rate of postoperative renal failure after LT.
Adult↗
Immunostaining for membrane attack complex of complement is related to cell necrosis in fulminant and acute hepatitis.
BACKGROUND/AIMS: Complement activation is one of the mechanisms involved in inflammatory lesions. Initiation of the complement terminal pathway at a cell surface leads to the formation of a cytolytic membrane attack complex. Our study assess whether a membrane attack complex-associated mechanism is involved in liver cell necrosis of fulminant and subfulminant hepatitis. METHODS: Immunostaining for membrane attack complex was compared with immunostaining for cytokeratin and complement inhibitory proteins such as membrane cofactor protein, decay-accelerating factor, and homologous restriction factor in 15 patients with fulminant hepatitis and 5 patients with nonfulminant acute hepatitis. RESULTS: In all patients, hepatocytes surrounding necrotic areas, but not those at a distance, were stained for membrane attack complex, whereas the opposite staining pattern for membrane cofactor protein was observed. In controls, no hepatocyte staining for membrane attack complex was observed, whereas membrane cofactor protein, but not decay-accelerating factor or homologous restriction factor, was detected on hepatocytes. CONCLUSIONS: Complement activation by antibody-dependent or non-antibody-dependent mechanisms might be involved in the pathogenesis of either fulminant or acute hepatitis. Modulation of membrane cofactor protein expression on hepatocytes might contribute to the sensitivity of hepatocytes to membrane attack complex and subsequent cell lysis.
Acute Disease↗
Effects of superior mesenteric artery stenosis on splanchnic and systemic hemodynamics in conscious rats with biliary cirrhosis.
BACKGROUND/AIMS: Since portal tributary blood flow is increased in portal hypertension due to cirrhosis, a reduction in mesenteric arterial blood flow should decrease portal pressure. METHODS: Calibrated stenosis of the superior mesenteric artery was performed in bile duct ligated rats, using a 22-gauge needle. Arterial stenosis was performed 4 weeks after bile duct ligation. Hemodynamic studies were performed in the 5th week following bile duct ligation in conscious rats. RESULTS: At that time, no digestive tract alterations were observed. In rats with mesenteric arterial stenosis, portal pressure was 12.2 +/- 2.0 mmHg; this value was lower than in rats with cirrhosis without arterial stenosis (14.5 +/- 1.1 mmHg) but higher than normal rats (5.8 +/- 0.7 mmHg). In rats with cirrhosis with mesenteric arterial stenosis, portal tributary and mesenteric blood flows were lower than in rats with cirrhosis without arterial stenosis and not significantly different from normal rats. In rats with mesenteric stenosis, cardiac index was significantly lower than in rats with cirrhosis and not significantly different from normal rats. CONCLUSION: This study shows that calibrated superior mesenteric arterial stenosis normalized portal tributary blood flow and reduced but did not normalize the degree of portal hypertension.
Animals↗
Temporary portocaval anastomosis with preservation of caval flow during orthotopic liver transplantation.
BACKGROUND: A novel technique of orthotopic liver transplantation was developed whereby both vena caval and portal venous blood flows are preserved during the entire procedure. PATIENTS AND METHODS: This method of liver transplantation was successfully performed in 51 consecutive patients and included a temporary portocaval shunt, a total hepatic resection with vena caval preservation, and an end-to-side cavocaval anastomosis. RESULTS: Preservation of vena cava and portocaval anastomosis were feasible in 51 patients (100%), including 34 patients with cirrhosis and 2 patients undergoing elective retransplantation. Both caval and portal flows were preserved during the entire procedure in 48 patients (94%). No venovenous bypass was required. Four deaths (7.8%) occurred postoperatively, all of them unrelated to the surgical procedure. CONCLUSION: We believe adoption of this orthotopic liver transplantation technique will obviate the need for venovenous bypass.
Humans↗
[Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma. Value and prognostic factors of hepatic artery embolization].
To assess efficiency and to determine prognostic factors in emergency embolization for intraperitoneal hemorrhage from hepatocellular carcinoma we retrospectively analyzed 12 consecutive procedures. In order to evaluate the extension of tumor thrombus in the intrahepatic portal system before embolization, a portal perfusion rate was defined as the relative patency of the segmental portal veins demonstrated at arteriography. Serum bilirubin level and portal perfusion rate were correlated with length of survival. Successful hemostasis was achieved in all patients. Mean length of survival was 149 days. Two patients are still alive 545 and 195 days, respectively, after the procedure. A significant correlation (p = 0.005) between portal perfusion rate and length of survival was obtained. There was no correlation between serum bilirubin level and prognosis. Emergency embolization is an effective treatment in patients with intraperitoneal hemorrhage from hepatocellular carcinoma. Prognosis depends of portal perfusion rate.
Aged↗
[Adenocarcinoma of the cardia: does the extent of gastric resection and lymph node excision influence survival?].
OBJECTIVES: In the curative treatment of the adenocarcinoma of the cardia (AC), the extent of the esogastrectomy and the need for lymph node dissection are still debated. The palliative treatment of AC is now currently non-surgical. The aim of this study was: a) to assess early results of palliative surgery; b) to evaluate the results of curative resection with reference to the influence of the extent of gastrectomy and lymph node dissection on early results and long-term survival. METHODS: From 1979 to 1989, 179 patients (mean age = 60 +/- 12 years) with AC had 45 palliative resections (mean age = 56 +/- 15) and 134 curative resections (mean age = 61 +/- 12). Thirty-eight proximal subtotal esogastrectomies (PSOG) and 7 total esogastrectomies (TOG) were palliative; 72 PSOG and 62 TOG extended to the spleen were curative and associated with lymphadenectomy. RESULTS: The operative mortality rate was 8.9% regardless of the palliative or curative intent of resection. After palliative resection, the mortality rate was 2.6% (1 case out of 38) after PSOG and 42.9% (3 cases out of 7) after OGT (P = 0.01); the median survival was 8 months. After curative resection, the mortality rate was 12.5% (9 cases out of 72) after PSOG and 4.8% (3 cases out of 62) after extended TOG (P = 0.2); actuarial 5-year survival rate was 42% after PSOG and 39% after extended TOG. CONCLUSIONS: These results suggest that: a) palliative PSOG for AC can be performed with a low mortality; b) resection with extensive lymphadenectomy allows substantial survival regardless of the extent of gastrectomy.
Adenocarcinoma↗
[Multiple carcinoid tumors of the small intestine].
Multiple carcinoid tumours of the small bowel with more than 3 lesions are very unusual. We report a case of a 44-year-old man who presented with more than 40 carcinoid tumours localized in the ileum, associated with hepatic metastases and carcinoid tricuspid valve involvement. The site of the primary tumour was not determined by usual imaging techniques. The patient underwent laparotomy in order to resect liver metastases. The diagnosis of multiple carcinoid tumours of the small bowel was made during the abdominal exploration. There was no intraepithelial endocrine cell hyperplasia in the mucosa adjacent to the small bowel tumours. After a 6-month follow-up, the carcinoid syndrome had completely disappeared.
Antineoplastic Combined Chemotherapy Protocols↗
Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid.
Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation.
Adolescent↗
Liver devascularisation improves the hyperkinetic syndrome in patients with fulminant and subfulminant hepatic failure.
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Adolescent↗
Mechanism of the abnormal vitamin K-dependent gamma-carboxylation process in human hepatocellular carcinomas.
BACKGROUND: An important marker for hepatocellular carcinoma is the presence of des-gamma-carboxy (abnormal) prothrombin. However, the molecular basis for the reduced carboxylation of prothrombin is unknown. METHODS: Two groups of patients were defined according to the absence (Group I, n = 7) or presence (Group II, n = 8) of des-gamma-carboxy prothrombin. The enzymatic activity of gamma-carboxylase and the total microsomal prothrombin concentration were determined in all tumors. The kinetic parameters for the synthetic peptide Phe-Leu-Glu-Glu-Leu (FLEEL) were measured in eight tumors. The gamma-carboxylase mRNA expression was evaluated by Northern blot analysis in 12 of 15 tumors. In addition, the total vitamin K content (K1, K1 epoxide, and menaquinones 4-10) in 10 tumors was investigated by high performance liquid chromatography. RESULTS: Concentrations of menaquinones 4-10 were normal in the nontumorous part of the liver but significantly decreased (P = 0.02) in all the tumors (Groups I and II). This decrease was more severe in Group II (P = 0.02). The tumors in Group I had normal or increased gamma-carboxylase activity and increased mRNA expression (P < 0.02) as compared with their nontumorous counterparts. The tumors in Group II were heterogeneous. Five tumors displayed low gamma-carboxylase activity, associated with low mRNA expression in two, whereas two others had high gamma-carboxylase activity and mRNA expression. The concentration of FLEEL at half-maximal velocity was normal in all the tumors examined (Groups I and II), and a relation was found between the level of expression of gamma-carboxylase and the maximal velocity for FLEEL carboxylation in the tumors in Group II (r = 0.98; P < 0.01). The microsomal content of normal prothrombin was within normal limits in all tumors (Groups I and II). CONCLUSIONS: Tumor vitamin K content has a critical role in the synthesis of des-gamma-carboxy prothrombin. Furthermore, the gamma-carboxylase defect, which is observed in some secreting tumors, is the result of the defective gene expression of a normal enzyme and not the consequence of the presence of a competitive inhibitor. It is possible that a 75% reduction in gamma-carboxylase gene expression could take a part in the secretion of des-gamma-carboxy prothrombin, but this mechanism is not predominant.
Biomarkers↗
Systemic release of interleukin-10 during orthotopic liver transplantation.
Experimental and clinical observations indicate that the liver allograft is less immunogenic than other organ transplants and can promote immune tolerance. Because interleukin-10 recently emerged as a macrophage and T-cell-derived cytokine with potent immunosuppressive properties, we studied its production in 28 patients undergoing orthotopic liver transplantation. Plasma levels of immunoreactive interleukin-10 dramatically increased within 2 hr after liver allograft reperfusion, with peak levels ranging between 214 and 4998 pg/ml (median = 677 pg/ml). This systemic release of interleukin-10 was transient because it returned to low levels by 48 hr (range = 26 to 51 pg/ml). The higher interleukin-10 levels measured in right atrial blood as compared with portal blood indicated that interleukin-10 was most likely synthesized within the liver graft. To get insight into the cellular origin of interleukin-10, we also measured serum levels of interleukin-4 and interferon-gamma, both produced by T cells, and interleukin-8, a cytokine secreted by macrophages, in eight patients. Interleukin-4 and interferon-gamma levels remained undetectable in most of the patients, whereas interleukin-8 levels paralleled those of interleukin-10. Portal endotoxemia was probably not involved in interleukin-10 production because endotoxin levels remained low (< 20 pg/ml) before and after liver allograft reperfusion. Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes. We conclude that orthotopic liver transplantation is associated with a massive release of interleukin-10 and interleukin-8, most likely produced by allograft macrophages.
Adult↗
Expression of complement-regulatory proteins in normal and UW-preserved human liver.
BACKGROUND/AIMS: Somatic cells are protected against complement-mediated injury by specialized membrane proteins, known as complement-regulatory proteins (CRP). The knowledge of the pattern of CRP expression in the liver is important to evaluate the role of complement-mediated injury in graft rejection. METHODS: We determined the distribution of four main CRP: membrane cofactor protein (MCP), decay accelerating factor (DAF), protectin, and complement receptor 1 (CR1) in 30 histologically normal livers, 13 samples from University of Wisconsin cold-storage solution (UW)-preserved tissue and 17 postoperative biopsies of UW-preserved allografts. RESULTS: In normal liver, hepatocytes expressed only MCP. Bile duct cells were reactive for MCP and protectin. Sinusoidal endothelial cells expressed MCP and protectin but displayed no or faint expression of DAF. Endothelial cells of portal vessels and centrilobular veins expressed high levels of DAF, MCP, and protectin. No expression of CR1 was observed. No change in CRP expression was usually detected after UW preservation, except for protectin, induced on hepatocytes in 9 samples of UW-preserved liver tissue and in 9 allografts. CONCLUSIONS: Hepatocytes and sinusoidal endothelial cells, which have a defective expression of CRP, might be at risk for complement-mediated injury. However, this risk is not aggravated after UW preservation.
Adenosine↗
Expression of cytokine-dependent adhesion molecules in postreperfusion biopsy specimens of liver allografts.
BACKGROUND/AIMS: Allogeneic recognition of donor cells by host T lymphocytes requires the expression of cytokine-dependent molecules, such as class II major histocompatibility antigens, intracellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 3 (LFA-3). In the liver, activation of Kupffer cells after ischemic injury during the transplantation procedure may result in an early induction of cytokine-dependent molecules. METHODS: The pattern of induction of ICAM-1, HLA-DR, HLA-DQ, and LFA-3 was investigated in 30 postreperfusion surgical biopsy specimens of liver allografts by an immunohistochemical technique. RESULTS: Two patterns of induction were observed: focal or diffuse. On hepatocytes, ICAM-1 was induced in 22 cases (11 focal, 11 diffuse), HLA-DR in 18 cases (13 focal, 5 diffuse), HLA-DQ in 13 cases (3 focal, 10 diffuse), and LFA-3 in 1 case (focal). On bile duct cells, HLA-DR was expressed in 19 cases, associated with HLA-DQ in 7 cases. No induction of ICAM-1 and LFA-3 was detected. Compared with the other patients, the group of patients with diffuse postoperative hepatocellular induction of ICAM-1 was characterized by higher preharvesting serum transaminase levels in the donor (P < or = 0.001), suggestive of preoperative ischemic injury, and increased incidence of acute graft rejection (P = 0.04). CONCLUSIONS: Preoperative warm ischemia may modify the immunogenicity of liver allografts.
Adult↗
The changing scene of hepatic vein thrombosis: recognition of asymptomatic cases.
BACKGROUND/AIMS: Hepatic vein thrombosis is thought to be manifested by ascites, abdominal pain, and hepatomegaly, with a uniformly poor prognosis. However, new imaging techniques allow for the diagnosis of hepatic vein thrombosis in asymptomatic cases. The aim of our study was to re-evaluate symptoms and prognosis in patients with hepatic vein thrombosis. METHODS: Eighty-one patients with hepatic vein thrombosis were analyzed. Forty-seven patients were admitted from 1970 to June 1987 (group I, before Doppler ultrasonography and magnetic resonance imaging were introduced at our hospital) and 34 from July 1987 to June 1991 (group II). RESULTS: When comparing the two groups, age, sex ratio, and causes of hepatic vein thrombosis did not differ. Eight group II patients (asymptomatic patients) had no ascites, hepatomegaly, or abdominal pain. One major hepatic vein remained patent in 41% of group II patients, compared with 12% in group I (P < 0.05). Intrahepatic collaterals were seen in 79% of group II patients, compared with 21% of group I patients (P < 0.01). All asymptomatic patients had large intrahepatic and portasystemic collaterals. At 3 years, death occurred in 22% of group II patients and in 45% of group I patients. No asymptomatic patient died. CONCLUSIONS: Asymptomatic hepatic vein thrombosis is associated with the spontaneous development of large intrahepatic and portosystemic collaterals. In asymptomatic patients, prognosis at 3 years seems to be good, and surgical therapy may not be required.
Adult↗