Prolonged decreases in plasma nitrate levels at early postoperative phase after hepato-pancreato-biliary surgery.
Satoi S. Kamiyama Y. Kitade H. Kwon AH. Yoshida H. Nakamura N. Takai S. Uetsuji S. Okuda K. Hara K. Takahashi H.
First Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and metabolic alterations. To evaluate the clinical significance of .NO production under surgical stress, serial measurements of plasma nitrite plus nitrate levels were performed in 45 surgical patients. Group A included 19 patients who underwent major surgery with uneventful postoperative courses. Group B included 18 patients who underwent laparoscopic cholecystectomy. Group C included 8 patients whose surgery was complicated by intra-abdominal abscesses. Eight healthy volunteers served as controls. Plasma nitrate levels were determined with a redox chemiluminescence .NO analyzer and coincided with measurements made by high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples). During laparotomy, arterial nitrate levels correlated well with peripheral, portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949, respectively; p < 0.0001). A significant decrease in nitrate from preoperative levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days after surgery. Plasma nitrate levels in groups A and B were significantly different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in group A (p < 0.005). Plasma nitrate levels measured before and after fasting or food intake were not significantly different. These results suggest that surgical stress leads to a decrease in the end product of .NO in the whole body, and that the greater the surgical stress the longer the duration of decreased .NO production.
Prevalence of antiphospholipid antibodies in patients with chronic liver disease related to alcohol or hepatitis C virus: correlation with liver injury.
Biron C. Andreani H. Blanc P. Ramos J. Ducos J. Guigue N. Michel H. Larrey D. Schved JF.
Department of Hepato-Gastroenterology, Hopital Universitaire Saint Eloi, Montpellier, France.
Antiphospholipid antibodies (APAs) have been reported in various clinical conditions. However, the pathogenesis and clinical significance of these antibodies are still unclear. The objective of this study was to assess the prevalence of APAs in patients with chronic alcohol- or hepatitis C virus (HCV)-related liver disease and to evaluate their relation to the underlying liver disease. We prospectively studied 201 patients referred to an hepato-gastroenterology department, including 77 patients with a history of alcohol abuse (group I) and 124 with chronic HCV infection (group II), and 107 healthy subjects (control population). Liver biopsy was performed in all patients. In cirrhotic patients, the severity of the liver disease was assessed with the use of Child's classification, as modified by Pugh. Several biologic parameters, including lupus anticoagulant and anticardiolipin antibodies, were determined. Forty-eight percent of patients in group I and 33% of those in group II had APAs. Among cirrhotic patients, APAs were more frequent in patients with Child grade B or C than in those with grade A severity. In patients with chronic HCV-related liver disease, a correlation was found between APA levels and liver fibrosis (P = 0.009); no relation was found between APA levels and histologic liver disease activity (P = 0.25). In the control group, one subject was APA-positive. None had lupus anticoagulant. APAs seem to be frequently associated with chronic liver disease of various causes. These results suggest further investigations on the potential role of these antibodies in fibrosis or liver injury.
Assessment of the hepatic circulation in humans: new concepts based on evidence derived from a D-sorbitol clearance method.
Molino G. Avagnina P. Belforte G. Bircher J.
Divisione di Medicina Generale, A Azienda Ospedaliera San Giovanni Battista, Turin, Italy.
D-Sorbitol (SOR) is safe, is easy to measure, and has an exceptionally high extraction ratio in the normal liver of 0.93+/-0.05 (mean+/-SD). Together with the general interest in hepatic hemodynamics, these facts motivated us to review the usefulness of this compound for the assessment of liver plasma flow in humans. We concluded that in subjects without liver disease the nonrenal clearance of SOR-measured noninvasively-very closely approximates hepatic plasma flow. Because of its lower and more variable extraction ratio, indocyanine green should no longer be used without hepatic vein catheterization. Even in patients with cirrhosis, SOR exhibits higher hepatic extraction ratios than indocyanine green. To fully explore the potential of SOR in the evaluation of such patients attention needs to be paid to the complex changes in architecture and function occurring in this disease. In cirrhotics the noninvasively measured nonrenal clearance of SOR presumably approximates the flow through intact and capillarized sinusoids (functional flow) and reflects the amount of blood having functional contact with hepatocytes. The theoretic background of the method, its accuracy, further research needs, and potentials of various approaches are discussed in detail.
Increased ascitic level of hyaluronan in liver cirrhosis.
Lai KN. Szeto CC. Lam CW. Lai KB. Wong TY. Leung JC.
Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam.
Hyaluronan (HA) is a polysaccharide that forms a critical component of extracellular matrixes. It is present in high concentrations in tissues undergoing remodeling and morphogenesis. Serum HA is elevated in patients with chronic liver disease, and this has been considered to be caused by impaired degradation by the liver endothelial cells. We studied the level of HA in the ascitic fluid and plasma from 27 patients with cirrhotic ascites. These values were compared with peritoneal dialysate effluent (PDE) and plasma from 33 patients with uremia who were undergoing continuous ambulatory peritoneal dialysis (CAPD). The median HA levels in ascitic fluid and plasma from our 26 patients with cirrhosis were significantly higher than corresponding PDE and plasma values from the 33 CAPD patients (p < 0.0001). The median peritoneal/plasma ratios of creatinine, albumin, and immunoglobulin G in either cirrhotic or CAPD patients were less than unity. In contrast, the median peritoneal/plasma ratios of HA in both groups of patients exceeded one with a higher peritoneal/plasma ratio of HA in patients with cirrhosis (p = 0.0035). A significant correlation was observed between the ascitic level of HA and interleukin-1beta, interleukin-6, or transforming growth factor-beta. Our in vitro cell culture studies revealed that HA is synthesized by both mesothelial cells and macrophages. We observed an additive effect in the synthesis of HA by mesothelial cells when the macrophage-conditioned medium was added to the RPMI culture medium. We conclude that a high level of HA is found in ascites from patients with cirrhosis. Our results strongly suggest that simultaneous increased synthesis of HA by the peritoneal cells and a reduction of degradation by liver endothelial cells occur in these patients with cirrhosis with ascites. This event of increased HA synthesis may be contributory to remodeling and regeneration of the peritoneal lining.