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PubMed2000

Superoxide dismutase activity in children with chronic liver diseases.

BACKGROUND/AIMS: Liver disease in infancy has multiple etiologies. As reactive oxygen intermediates are involved in several types of tissue damage, we have investigated whether different forms of liver disease in infancy are associated with increased free radical generation, using an indirect approach in which superoxide dismutase (a free radical scavenger) activity is determined in the liver tissue. METHODS: A total of 48 liver biopsies performed at diagnosis were evaluated retrospectively. Nine infants had biliary atresia, eight Alagille syndrome, seven alantitrypsin deficiency and 12 cryptogenic hepatitis. As controls we studied 12 biopsies with normal histology obtained from seven children with portal vein thrombosis and five children who underwent biopsy for management reason but had no liver disease. Superoxide dismutase activity in liver biopsy specimens was measured using the cytochrome C method by spectrophotometry and expressed as U SOD/mg protein. RESULTS: Superoxide dismutase activity was significantly increased in biliary atresia (1.25 +/- 0.56 U SOD/mg protein, p<0.0001) and Alagille syndrome (1.31 +/- 0.56 U SOD/mg protein, p<0.0001) as compared with al-antitrypsin deficiency (0.75 +/- 0.3 U SOD/mg protein), neonatal hepatitis (0.72 +/- 0.37 U. SOD/mg protein) and normal controls (0.4 +/- 0.7 U. SOD/mg protein). The highest level of SOD activity was found, however, in control children with portal vein thrombosis (2.09 +/- 0.96 U SOD/mg protein; p<0.0001 as compared to the other groups). CONCLUSION: Superoxide dismutase, a key enzyme in free radical protection, is increased significantly in the liver tissue of infants with cholestatic liver disease due to bile duct damage and in children with portal vein thrombosis, suggesting that products of free radical reactions are involved in the pathogenesis of these disorders.

Alagille Syndrome↗
PubMedDate not supplied

Transjugular intrahepatic portosystemic shunt in portal vein thrombosis: role of the right gastric vein with anomalous insertion.

Transjugular intrahepatic portosystemic shunt (TIPS) was performed in two patients with portal vein thrombosis. In both patients, hepatopetal flow had been maintained by an anomalous insertion of the right gastric vein (RGV) into the portal vein bifurcation and into the left portal branch respectively. In one patient, the main portal trunk could not be recanalized and the RGV was used as an accessory portal vein to place one stent for TIPS. In the other case, access through the partial portal-vein occlusion was gained and three stents were placed from the hepatic vein to the main portal vein distal to the thrombus. In portal vein thrombosis, the aberrant insertion of the RGV into the left or right portal branches may maintain patency of the intrahepatic portal system and, in case of unsuccessful recanalization of the porta, may represent the sole pathway for placing a TIPS.

Collateral Circulation↗
PubMed1992

Ultrasonographic findings in a cow with ascites due to thrombosis of the caudal vena cava.

This case report describes a three-year-old Swiss Braunvieh cow with ascites due to thrombosis of the caudal vena cava. Ultrasonography verified the ascites and revealed dilatation of the abdominal portion of the caudal vena cava (4.8 cm). It was presumed that the caudal vena cava was occluded by a thrombus or by perivenous compression cranial to the dilatation. Post mortem findings included: a massive accumulation of fluid in the abdominal cavity; a 15 cm long thrombus in the subphrenic region of the caudal vena cava; multiple pulmonary abscesses; severe thrombosis of the pulmonary vasculature; hepatic congestion; oedematous abomasal folds; and severe thrombophlebitis of the left jugular vein and both udder veins, due to poor intravenous injection technique. Ascites caused by thrombosis of the caudal vena cava is rare because collateral routes of venous return, including the udder veins, are usually established. It was therefore concluded that the ascites was attributable to bilateral thrombosis of the udder veins.

Animals↗
PubMed1993

Surgical techniques and innovations in living related liver transplantation.

The authors successfully performed a series of 33 living related liver transplantations (LRLT) on children (15 males and 18 females, ranging from 7 months to 15 years of age) from June 1990 to May 1992, with the informed consent of their parents and the approval of the Ethics Committee of Kyoto University. Before operation, six of the children required intensive care, another 14 were hospitalized, and 13 were homebound. Donors (12 paternal and 21 maternal) were selected solely from the parents of the recipients on the basis of ABO blood group and graft/recipient size matching determined by computed tomography scanning. Procurement of graft was performed using ultrasonic aspirator and bipolar electrocautery without blood vessel clamping and without graft manipulation. All donors subsequently had normal liver function and returned to normal life. The left lateral segment (16 cases), left lobe (16 cases), or right lobe (one case) were used as grafts. The partial liver graft was transplanted into the recipient who underwent total hepatectomy with preservation of the inferior vena cava using a vascular side clamp. Twenty-seven of 33 recipients are alive and well with the original graft and have normal liver function. The patient survival rate was 89% (24/27) in elective cases and 50% (3/6) in emergent cases. The other six recipients had functioning grafts but died of extrahepatic complications. Complications of the graft were minimal in all cases. Hepatic vein stenosis, which occurred three times in two cases, was successfully treated by balloon dilatation. In cases with sclerotic portal vein, the authors anastomosed the portal vein of the graft to the confluence of the splenic vein and the superior mesenteric vein without a vascular graft, after experiencing a case of vascular graft thrombosis. After hepatic artery thrombosis occurred in one of the initial seven recipients whose arterial anastomosis was done with surgical loupe, microsurgery was introduced for hepatic artery reconstruction. There has been no occurrence of thrombosis since then. The current results with LRLT suggested that the meticulous management of surgical factors at each stage of the LRLT procedure is crucial for successful outcome. Living related liver transplantation is a promising option for resolving the graft shortage in pediatric liver transplantation and may be regarded as an independent modality to supplement cadaver donation.

Adolescent↗
PubMedDate not supplied

Hemodynamic changes in blood flow through the denervated liver in pigs.

We investigated the effects of liver denervation on hemodynamic circulation in seven anesthetized pigs. Simultaneous measurements of the hepatic artery and portal vein were performed with an ultrasound Doppler flow meter before and after liver denervation. Neither resting systemic nor hepatic hemodynamics changed following liver denervation. However, temporary occlusion of the portal vein resulted in a significant increase in hepatic artery flow in the innervated liver (from 123 +/- 15 ml/min to 177 +/- 17 ml/min, p < .01), whereas, in the denervated liver, a significant decrease was observed (from 128 +/- 11 ml/min to 106 +/- 19 ml/min, p < .05). Thus, the reciprocity between the hepatic artery and portal vein in the hepatic artery flow during portal vein occlusion might intensify symptoms of portal vein thrombosis in liver transplantation. In the denervated liver, a significant decrease also occurred in systolic blood pressure and central venous pressure from 1 to 3 min after portal vein occlusion. Since the liver plays a crucial role in the maintenance of cardiovascular homeostasis during blood loss, it is likely that denervation at the porta hepatis induced a lack of vasoconstriction in the portal territory. Liver denervation might further exacerbate this response to hypotension. The current study confirms that the hepatic nerves play an important role in hepatic arterial and portal venous interactions aimed at maintaining a constant blood flow through the liver. We also suggest that the hepatic nerves are important for cardiovascular homeostasis.

Animals↗
PubMed1992

Venoocclusive liver disease after bone marrow transplantation: findings at duplex sonography.

Ascites, thickening of the gallbladder wall, and reversal of portal flow are documented sonographic findings in venoocclusive disease of the liver. The frequency and specificity of these findings and their relationship to the severity of this disease have not been studied. In an attempt to clarify these issues, 65 patients who had bone marrow transplantations were prospectively studied with serial B-scans and duplex color Doppler sonography. For all patients, assessment included liver size and texture, thickening of the gallbladder wall (greater than 10 mm), and presence of ascites. Doppler flow velocity profiles were obtained from the portal vein, hepatic veins, and inferior vena cava. The hepatic artery resistive index (RI) was calculated. Twenty volunteers were also studied to establish normal flow values. Nineteen patients had documented venoocclusive disease, nine had hepatic graft-vs-host disease (GVHD) (five after proved venoocclusive disease), two had hepatitis, and 40 had no clinical or biochemical evidence of liver injury after bone marrow transplantation. Ascites (n = 16), thickening of the gallbladder wall (n = 8), hepatomegaly (n = 8), and altered liver texture (n = 3) were not distinguishing features of venoocclusive disease. Mean hepatic artery RI was as follows (ranges are in parentheses): control group, 0.69 (0.58-0.76); venoocclusive disease patients, 0.81 (0.75-0.87); GVHD patients, 0.69 (0.63-0.71); all other patients after bone marrow transplantation, 0.66 (0.61-0.71). The RI values in venoocclusive disease were significantly elevated, but an incremental rise in RI with increasing severity of the disease was not seen. Abnormalities in portal vein flow were seen in only two patients: in one with fatal venoocclusive disease, reversed portal flow developed, and in one with GVHD, portal vein thrombosis developed. Contrary to previous reports, no correlation between abnormalities in portal flow and venoocclusive disease was seen. Flow velocities in the hepatic veins and the inferior vena cava were not significantly different from values in the volunteer group. These results suggest that a significant elevation of the hepatic artery RI may be a sensitive index of liver damage related to venoocclusive disease after bone marrow transplantation and an important distinguishing sonographic feature.

Blood Flow Velocity↗
PubMed2001

Outcome and hepatic hemodynamics in liver transplant patients with portal vein arterialization.

UNLABELLED: Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.

Adult↗
PubMed2005

Arterialisation of the portal vein as a model for the induction of hepatic fibrosis: description of microsurgical models in the rat.

Within the framework of liver transplantation, arterialisation of the portal vein in the case of non-recanalisable thrombosis has been reactivated. However, one of the consequences of this vascular reconstruction is the development of hepatic fibrosis. Clinical experience has shown that the development of fibrosis can be avoided by reducing portal inflow. We present, as a model for the induction of hepatic fibrosis, techniques of PVA, including transplantation. For PVA, several different techniques were used: the first with reduction of the portal inflow over a stent inserted in the right renal artery (PVA-B), the second with unrestricted flow using an aortic-portal segment (PVA-APS). The third technique was orthotopic liver transplantation with unrestricted portal arterialisation (OLTx-APS). Portal blood flow was measured with an ultrasonic flow probe. To determine the degree of hepatic fibrosis the amount of hydroxyproline was measured. Quantification of relative transcript levels of procollagen I was effected with real-time PCR using the TaqMan technology on a lightcycler instrument. The extracellular matrix was visualised with picro-sirius staining. Measurements with the ultrasonic probe showed a significant increase in flow rates, both with reduced (PVA-B) and unrestricted inflow (PVA-APS; OLTx-APS). The lowest survival rate (58%) was found in the group with unrestricted portal inflow. The reason for this was a high rate of thrombosis in the in the portal vascular tree (4 out of 12). In the OLTx-APS group four animals died within the first 3 postoperative days (69%), as a result of protracted postoperative shock. The overall survival rate was the highest (85%) in the group undergoing PVA with reduction of the portal inflow. PVA with unrestricted inflow was followed by a significant increase in extracellular collagen, which showed a clear correlation with the increase in the amount of hydroxyproline, the level of the mRNA for procollagen I and picro-sirius staining. With the operative PVA techniques presented herein, different arterial flow rates in the portal vein can be investigated. In our opinion these techniques represent an excellent animal model for studying the genesis of fibrosis and antifibrotic substances. By regulating the blood flow in the arterialised portal vein hepatic fibrosis can be reduced or even avoided. After a brief period of learning the microsurgical techniques, the surgeon can limit clamping times and achieve good results with these techniques.

Animals↗
PubMed1987

Endoscopic sclerotherapy or selective embolisation of esophageal varices. An endoscopic and portographic study in an experimental model.

In an experimental animal model with portal hypertension and esophageal varices, endoscopic sclerotherapy of the varices with Aethoxysclerol was compared with selective embolisation of the coronary vein with absolute ethanol. After 4 courses of endoscopic sclerotherapy the varices were permanently obliterated, as documented by portography and endoscopy. Selective embolisation also caused obliteration of the coronary vein and varices, but early and repeated recanalisation occurred, and permanent obliteration was only obtained when embolisation was combined with endoscopic sclerotherapy. Portal vein thrombosis occurred when embolisation was repeated more than 3 times. Hepatic blood flow was significantly higher in animals treated by endoscopic sclerotherapy than in nontreated controls and animals treated by selective embolisation alone.

Animals↗
PubMed1999

Nonalcoholic steatohepatitis: a toxic liver disease in industrial workers.

AIMS: Occupational/environmental exposure to hepatotoxins has recently been implicated in nonalcoholic steatohepatitis (NASH). The aims of this study were to determine the presence and frequency of NASH in a large group of workers chronically exposed to several volatile petrochemical products in an industrial area in north-east Brazil and to observe its course in workers removed from the work environment. METHODS: 1500 asymptomatic workers were screened with standard liver blood tests during 1994-5. Those with elevated transaminases (>3x normal) on 3 occasions were evaluated further both clinically and with serum HBsAg, anti-HCV, ferritin, lipids and autoantibody determination. Patients with either no etiological diagnosis, positive HBsAg/anti-HCV serology and/or excess alcohol intake underwent liver biopsy. Those with obesity, diabetes or an isolated abnormal GGT were excluded. Of workers diagnosed as having NASH (compatible histology and no excess alcohol intake), a proportion were removed from the work environment and evaluated monthly with liver blood tests and a repeat liver biopsy 8-14 months later. RESULTS: 112 workers had abnormal transaminases and 32 fulfilled the criteria for liver biopsy. 20 of these were classified as NASH, the remainder had viral hepatitis (n = 6), alcoholic liver disease (n = 5) or portal vein thrombosis (n = 1). In all of the 10/20 who were removed from the work environment, their aminotransferases and GGT gradually decreased and their histology improved. CONCLUSIONS: These results demonstrate that NASH can occur following chronic exposure to volatile petrochemical substances in the workplace. Exposed workers should be regularly screened for the presence of liver damage and ideally removed from the work environment where possible.

Adult↗
PubMed1990

Intrahepatic portal venous system: variations demonstrated with duplex and color Doppler US.

Seventeen cases of variations of the intrahepatic portal venous system were investigated with use of duplex and color Doppler ultrasound (US). Seven cases involved absence of the horizontal segment of the left portal vein, with portal supply to the left lobe arising from the right lobe. The 10 remaining cases involved variations of intrahepatic portal branching resulting from absence of the right portal vein, taking four patterns. It is thought that these findings represent variants of normal. These variants are important in two settings: in planning hepatic surgery and in the differential diagnosis of chronic portal vein thrombosis.

Adult↗
PubMed2003

The value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications.

OBJECTIVE: To assess the value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications. METHODS: Forty-one patients after orthotopic liver transplantation were examined by using color Doppler flow imaging to observe the hepatic blood flow and change of ultrasonography of the hepatic parenchyma and bile duct. The measured indexes included maximum blood flow velocity, time-average blood flow velocity (TAV), resistance index (RI) and diameter of the bile duct. RESULTS: Among 41 patients, 17 (41.5%) suffered from liver transplant rejection. Of the 17 patients, 13 (76.4%) showed decrease of TAV of the portal vein, 15 (88.25%) low-amplitude single-phase serrated wave or negative biphasic wave of the hepatic vein, 9 (52.9%) increased hepatic arterial RI, and 5 (29.4%) slightly dilated bile duct. Sonography showed disappearance of the hepatic artery blood flow around the portal vein in 5 (12.2%) of the 41 patients with hepatic artery thrombosis in the postoperative period. Slight dilatation of the intrahepatic bile duct was found in 3 (7.3%) of the 41 patients in the early postoperational period and it normalized within 2 weeks. Ultrasonography of 20 patients (48.8%) revealed a visible dilatation of the intrahepatic bile duct, which was worsening gradually. The causes of bile duct dilatation included biliary stricture in 2 patients (10%), stone in 15 patients (75%) and others in 3 patients (15%). CONCLUSIONS: Color Doppler ultrasonography is valuable for monitoring normal liver transplantation and postoperative complications.

Bile Duct Diseases↗