Circulating soluble cytochrome c in liver disease as a marker of apoptosis

OBJECTIVES: To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. DESIGN: Laboratory research study with comparison group. SETTING: Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. SUBJECTS: A total of 108 patients with liver disease and 30 healthy controls. INTERVENTIONS: Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme-linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick-end-labelling (TUNEL) assay. MAIN OUTCOME MEASURES: Soluble cytochrome c level by type of liver disease by clinical and histological findings. RESULTS: Soluble cytochrome c concentration (mean 187.1 +/- 219.5 ng x mL(-1)) was significantly higher in patients with liver disease than in controls (39.8 +/- 35.1 ng x mL(-1); P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 +/- 2844.8 ng x mL(-1); P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 +/- 297.0 ng x mL(-1)) than the portal vein (mean 169.2 +/- 143.3 ng x mL(-1)), and it was highly detectable in bile (mean 2288.0 +/-4596.0 ng x mL(-1)) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 +/-304.3 ng x mL(-1)) than treated patients (77.9 +/- 35.8 ng x mL(-1); P = 0.001). CONCLUSIONS: Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis.     

Effect of HSP70 induced by warm ischemia to the liver on liver function after partial hepatectomy

BACKGROUND/AIMS: The purpose of this study was to determine if induction of HSP70 (heat shock protein 70), a stress protein which plays a cytoprotective role in response to various stimuli, protects hepatocytes from damage caused by partial hepatectomy and, if so, to elucidate the mechanism of such protection. METHODOLOGY: One hundred and eight male F344 rats weighing 190-220 g were randomly assigned to two groups with or without the presence of preconditioning. Fifteen-minute warm ischemia was applied to the liver of rats to induce HSP70, and 70% hepatectomy was performed 48 hours after the induction of HSP70 (ischemia group; n = 72). The rats in the nonischemia group did not undergo 15-min warm ischemia prior to 70% hepatectomy (nonischemia group; n = 36). Six rats, selected randomly from each group, were sacrificed at each measurement point to obtain blood and liver tissue samples. The levels of HSP70 in the liver, serum nitric oxide, levels of catalase and superoxide dismutase activity in the liver as antioxidative enzymes, and levels of Bcl-xL and Bax proteins and caspase-3-like activity in the liver as indices of apoptosis, were measured. RESULTS: The mean +/- SD level of HSP70 in the ischemia group (100 +/- 42 arbitrary unit (au)) was significantly higher than that of the nonischemia group (2 +/- 0.7 au) immediately before hepatectomy (P < 0.05). The ischemic preconditioning attenuated the liver damage caused by the subsequent partial hepatectomy. The levels of superoxide dismutase and catalase activity, serum nitric oxide level, and Bax protein level of the ischemia and nonischemia groups showed no significant differences after the partial hepatectomy. In contrast, the mean +/- SD level of Bcl-xL in the liver of the ischemia group (261 +/- 52 au) was significantly higher than that in the nonischemia group (114 +/- 33 au) 12 hours after the hepatectomy (P < 0.01). Furthermore, the mean +/- SD level of caspase-3-like activity in the liver of the ischemia group (18.1 +/- 4.6 au) was significantly lower than that of the nonischemia group (26.0 +/- 4.8 au) at 12 hours after the hepatectomy (P < 0.05). CONCLUSIONS: HSP70 induced by ischemic preconditioning prior to the partial hepatectomy was considered to protect the liver itself. In addition, the induced HSP70 may affect the Bcl-xL level after partial hepatectomy. Therefore, Bcl-xL seems to be involved in the reduction of liver damage after partial hepatectomy along with HSP.     

101 hepatectomies under continuous inflow occlusion following simple in-situ liver cooling in patients with chronic liver diseases

BACKGROUND/AIMS: Hepatic inflow occlusion involves the serious disadvantage of ischemic injury to the remnant liver, particularly in patients with injured parenchyma. Liver hypothermia is one of the solutions for this problem. The purpose of this study was to evaluate simple in-situ liver cooling method of performing hepatic resection under continuous inflow occlusion in patients with chronic liver disease. METHODOLOGY: One hundred and one patients with chronic hepatitis (n = 26) and cirrhosis (n = 75) were included in this retrospective study. They underwent hepatectomy under conditions of continuous inflow occlusion immediately following simple in-situ liver cooling. Laboratory data and intraoperative and postoperative variables were analyzed for the three groups of patients stratified according to the lowest liver tissue temperature achieved: group 1 (> or = 30 degrees C, n = 16), group 2 (< 30 degrees C and > or = 25 degrees C, n = 62) and group 3 (< 25 degrees C, n = 20). RESULTS: Our simple in-situ liver cooling method enabled us to safely resect chronically diseased liver under continuous inflow occlusion (49.8 +/- 7.7 min, mean +/- SD; range, 30 to 70 min) with acceptable operative blood loss (894 +/- 853mL), morbidity (22.7%, 23/101) and mortality (1.0%, 1/101); one patient died of complications unrelated to ischemic injury. Analysis demonstrated that simple liver hypothermia was substantially hepatoprotective against ischemic injury in terms of serum transaminase levels and duration of inflow occlusion, particularly when the liver tissue temperature fell below 30 degrees C (groups 2 and 3). CONCLUSIONS: Hepatic inflow occlusion can be safely employed in a continuous manner for approximately 1 hour, even during resection of chronically diseased liver, particularly when the liver is cooled below 30 degrees C prior to hepatic clamping by our simple in-situ hypothermia technique.     

Hepatitis C infection in African Americans: its natural history and histological progression

OBJECTIVE: The aim of this retrospective analysis was to determine the natural history of hepatitis C virus infection in African Americans versus non-African Americans by evaluating the clinical, virological, and histological findings. METHODS: We examined in a retrospective manner the demographics, mode of infection, virological features, and histological progression of HCV infection in African Americans versus non-African Americans. There were 355 patients who met criteria based on adequate liver biopsy specimens and exclusion of other hepatic diseases. RESULTS: African Americans (n = 112) were significantly more likely to be infected with genotype 1 virus (88%) than were non-African Americans (n = 243; 67%; p < or = 0.001). Baseline HCV RNA levels were similar, although baseline ALT values were significantly lower in African Americans (80.0 microl +/- 5.5 vs 112.1 microl +/- 6.2; p < or = 0.001). African Americans were significantly older at the time of presentation and were significantly more likely to be women (p < or = 0.02). In African Americans, there was a trend toward less cirrhosis (22% vs 30%; p < or = 0.1) and significantly less piecemeal necrosis on liver biopsy. Non-African Americans had significantly higher fibrosis scores, ALT values, and piecemeal necrosis ratings, and tended to progress more rapidly to cirrhosis. This difference in histological progression between the two groups was not explained by differences in alcohol consumption. CONCLUSION: The lower ALT, piecemeal necrosis scores, and slower progression of fibrosis in African Americans may reflect less immunological recognition of HCV-infected liver cells.     

The effect of ursodeoxycholic acid on liver regeneration after partial hepatectomy in rats with non-alcoholic fatty liver disease

Aim:  To investigate the effect of ursodeoxycholic acid (UDCA) on liver regeneration following partial hepatectomy in rats with non-alcoholic fatty liver disease (NAFLD).
Methods:  UDCA was administered to seven rats (group 1) and physiological saline was administered both to seven rats (group 2) with NAFLD and to seven rats with normal livers (group 3). All rats underwent two-thirds hepatectomy and the remnant liver tissues were removed 48 h later. Mitotic index (MI) and levels of proliferating cell nuclear antigen (PCNA), glutathione (GSH) and malondialdehyde (MDA) were assayed.
Results:  MI and PCNA levels in group 2 were significantly lower than in groups 1 and 3, but the values in groups 1 and 3 were similar. The GSH levels of group 2 were significantly lower than those of group 3 in the hepatectomy tissues, and lower than those of groups 1 and 3 in the remnant tissues. The differences between GSH levels in groups 1 and 3 were not significant. MDA levels in hepatectomy and remnant tissues were significantly higher in group 2 compared to groups 1 and 3; values in groups 1 and 3 were similar.
Conclusion:  UDCA increases regeneration after partial hepatectomy in rats with NAFLD, possibly due to an attenuating effect on oxidative stress.     

Six Minute Walk Test to assess functional capacity in chronic liver disease patients

AIM： TO examine the utility of Six Minute Walk Test （6MWT） in patients with chronic liver disease （CLD）.
METHODS： Two hundred and fifty subjects between the ages of 18 and 80 （mean 47） years performed 6MWT and the Six Minute Walk Distance （6MWD） was measured.
RESULTS： The subjects were categorized into four groups. Group A （n = 45） healthy subjects （control）; group B （n = 49） chronic hepatitis B patients; group C （n = 54） chronic hepatitis C patients; group D （n = 98） liver cirrhosis patients. The four groups differed in terms of 6MWDs （P 〈 0.001）. The longest distance walked was 421 ± 47 m by group A, then group B （390 ± 53 m）, group C （357 ± 72 m） and group D （306 ± 111 m）. The 6MWD correlated with age （r = -0.482, P 〈 0.01/, hemoglobin （r = ＋0.373, P 〈 0.001） and albumin （r = ＋0.311, P 〈 0.001） levels. The Child-Pugh classification was negatively correlated with the 6MWD in cirrhosis （group D） patients （r = -0.328, P 〈 0.01）. At the end of a 12 mo follow-up period, 15 of the 98 cirrhosis patients had died from disease complications. The 6MWD for the surviving cirrhotic patients was longer than for non-survivors （317 ± 101 vs 245±145 m, P = 0.021; 95% CI 11-132）. The 6MWD was found to be an independent predictor of survival （P = 0.024）.
CONCLUSION： 6MWT is a useful tool for assessing physical function in CLD patients. We suggest that 6MWD may serve as a prognostic indicator in patients with liver cirrhosis.     

Role of ultrasonically activated scalpel in hepatic resection: a comparison with conventional blunt dissection

BACKGROUND/AIMS: Our goal was to compare the benefits and complications of using an ultrasonically activated scalpel (UAS) and conventional blunt dissection in hepatic resection. METHODOLOGY: We evaluated the effectiveness of dividing the liver by UAS (n=18) (the UAS group) compared with conventional blunt dissection (n=34) (the BD group) in patients undergoing hepatic resection. In the UAS group, UAS was used to dissect the superficial parenchyma and a crushing and clamping technique was used to divide the deep parenchyma. RESULTS: No serious complications attributable to the use of UAS were encountered, and there were no significant differences in morbidity or mortality between the two groups. The duration of surgery was significantly longer in the UAS group (281 +/- 81 min) than in the BD group (223 +/- 76 min) (P<0.05), and in the UAS group as a whole there were no advantages in using the new scalpel. However, when we compared only those patients who underwent minor hepatectomy, the intraoperative blood loss was significantly less in the UAS group (657 +/- 588mL) than in the BD group (1447 +/- 984mL) (P=0.03). The duration of drainage from the hepatic stump in these patients was also significantly shorter in the UAS group (P=0.02). CONCLUSIONS: The UAS is a useful new device for transection of the liver during hepatic resection. It may reduce the amount of blood loss during liver surgery, particularly in minor hepatectomy.     

Pure laparoscopic hepatectomy as repeat surgery and repeat hepatectomy

AIM:To assess clinical outcomes of laparoscopic hepatectomy(LH) in patients with a history of upper abdominal surgery and repeat hepatectomy.METHODS:This study compared the perioperative courses of patients receiving LH at our institution that had or had not previously undergone upper abdominal surgery.Of the 80 patients who underwent LH,22 had prior abdominal surgeries,including hepatectomy(n = 12),pancreatectomy(n = 3),cholecystectomy and common bile duct excision(n = 1),splenectomy(n = 1),total gastrectomy(n = 1),colectomy with the involvement of transverse colon(n = 3),and extended hysterectomy with extensive lymph-node dissection up to the upper abdomen(n = 1).Clinical indicators including operating time,blood loss,hospital stay,and morbidity were compared among the groups.RESULTS:Eighteen of the 22 patients who had undergone previous surgery had severe adhesions in the area around the liver.However,there were no conversions to laparotomy in this group.In the 58 patients without a history of upper abdominal surgery,the median operative time was 301 min and blood loss was 150 m L.In patients with upper abdominal surgical history or repeat hepatectomy,the operative times were 351 and 301 min,and blood loss was 100 and 50 m L,respectively.The median postoperative stay was 17,13 and 12 d for patients with no history of upper abdominal surgery,patients with a history,and patients with repeat hepatectomy,respectively.There were five cases with complications in the group with no surgical history,compared to only one case in the group with a prior history.There were no statistically significant differences in the perioperative results between the groups with and without upper abdominal surgical history,or with repeat hepatectomy.CONCLUSION:LH is feasible and safe in patients with a history of upper abdominal surgery or repeat hepatectomy.     

Selective suppression of initial cytokine response facilitates liver regeneration after extensive hepatectomy in rats

BACKGROUND/AIMS: After extensive hepatectomy, the cytokine network plays an important role in injury to the remnant liver and subsequent impairment of liver regeneration. Tumor necrosis factor alpha (TNF alpha) and interleukin 1beta (IL-1beta) are thought to be the initial cytokines associated with liver injury as well as with regeneration. We investigated the effect of the suppression of these cytokines on liver function and on liver regeneration after subtotal hepatectomy in rats. METHODOLOGY: Following 90% hepatectomy, rats were divided into two groups. Animals in the FR group received intraperitoneal FR167653, a selective inhibitor of TNF alpha and IL 1beta, while those in the Control group received vehicle only. Liver chemistry and serum levels of TNF alpha and IL-6 were measured serially. Liver specimens were obtained 48 hr after surgery and regenerative activity assessed by proliferating cell nuclear antigen (PCNA) expression and remnant liver weight. RESULTS: The survival rate was significantly better in the FR group (76.4+/-11.7 hrs) than in the Control group (26.8+/-4.3 hrs, p=0.0014). Liver enzyme and blood sugar levels after surgery were higher in the FR group compared to the Control group (p=0.03 or less). Changes in serum levels of both TNF alpha and IL-6 were suppressed in FR group rats after surgery. Microscopically, hepatocellular damage and steatosis was less prominent in FR group livers. PCNA labeling index and residual liver weights were higher in the FR group (p<0.001). CONCLUSIONS: Following extensive hepatectomy in rats, suppression of early cytokine induction improved liver function and facilitated liver regeneration. Suppression of selective cytokine responses could allow extended liver resection and reduced risk of liver failure.     

Low central venous pressure reduces blood loss in hepatectomy

AIM:To investigate the effect of low central venouspressure(LCVP)on blood loss during hepatectomy forhepatocellular carcinoma(HCC).METHODS:By the method of sealed envelope,50 HCC patients were randomized into LCVP group(n=25)and control group(n=25).In LCVP group,CVP was maintained at 2-4 mmHg and systolic bloodpressure(SBP)above 90 mmHg by manipulation of thepatient's posture and administration of drugs duringhepatectomy,while in control group hepatectomy wasperformed routinely without lowering CVP.The patients'preoperative conditions,volume of blood loss duringhepatectomy,volume of blood transfusion,length ofhospital stay,changes in hepatic and renal functionswere compared between the two groups.RESULTS:There were no significant differences inpatients' preoperative conditions,maximal tumordimension,pattern of hepatectomy,duration of vascularocclusion,operation time,weight of resected liver tissues,incidence of post-operative complications,hepatic andrenal functions between the two groups.LCVP group hada markedly lower volume of total intraoperative bloodloss and blood loss during hepatectomy than the controlgroup,being 903.9±180.8 mL vs 2 329.4±2 538.4(W=495.5,P<0.01)and 672.4±429.9 mL vs 1662.6±1932.1(W=543.5,P<0.01).There were no remarkabledifferences in the pre-resection and post-resection bloodlosses between the two groups.The length of hospitalstay was significantly shortened in LCVP group ascompared with the control group,being 16.3±6.8 d vs21.5±8.6 d(W=532.5,P<0.05). CONCLUSION:LCVP is easily achievable in technique.Maintenance of CVP≤4 mmHg can help reduce bloodloss during hepatectomy,shorten the length of hospitalstay,and has no detrimental effects on hepatic or renalfunction.     

Splenic arterial ligation prevents liver injury after a major hepatectomy by a reduction of surplus portal hypertension in hepatocellular carcinoma patients with cirrhosis.

BACKGROUND/AIMS: In this study, we investigated whether a reduction of surplus portal hypertension after a major hepatectomy by SPL (splenic arterial ligation) prevents a liver injury in cirrhotic patients with hepatocellular carcinoma. METHODOLOGY: Six hepatocellular carcinoma patients (SPL group) with liver cirrhosis (67 +/- 10 years old, ICGR15: 21.0 +/- 9.8%, T.Bil: 1.1 +/- 1.2 mg/dL) underwent major hepatectomy with splenic arterial ligation in order to reduce excessive portal hypertension after hepatectomy from 1998 to 2000, July. The patients (n = 15, 60 +/- 9 years old, ICGR15: 11.5 +/- 5.9%, T.Bil: 0.66 +/- 0.15 mg/dL) who underwent liver resection above subsegmentectomy in the same period (control group) served as the control for SPL group. RESULTS: In the SPL group, the portal pressures before hepatectomy were 26 +/- 7 cm H2O and those after hepatectomy were 29 +/- 6 cm H2O. The portal pressure after splenic arterial ligation decreased to 24.5 +/- 6.3 cm H2O. The splenic tissue blood flows before SPL were 16.8 +/- 5.6 mL/min/100 g, while those after SPL were 7.2 +/- 2.2 mL/min/100 g. The portal pressures before hepatectomy were 17 +/- 2 cm H2O and those after hepatectomy were 19 +/- 2 cm H2O in the six control patients. At the peak levels of liver function after surgery, T.Bil was 2.6 +/- 1.5 mg/dL, GOT was 165 +/- 59 IU/L, and GPT was 107 +/- 49 IU/L. All patients could discharge without complications except for one case with bile leakage in SPL. At the peak levels of liver function in control group, T.Bil was 3.7 +/- 1.9 mg/dL, GOT was 404 +/- 227 IU/L, and GPT was 322 +/- 171 IU/L. At the peak levels of liver function after surgery, T.Bil was 3.4 +/- 1.3 mg/dL, GOT was 398 +/- 289 IU/L, and GPT was 319 +/- 220 IU/L. Conversely, there were 11 episodes of complications (11/15), including two cases of hospital death resulting from liver failure in patients who underwent right lobectomy, in the control patients. CONCLUSIONS: The decompression of surplus portal hypertension by SPL might be effective in the prevention of post hepatectomized liver injury and the improvement of postoperative mortality and morbidity.     

Apheresis Therapy for Living‐Donor Liver Transplantation

Abstract: Liver transplantation is a fundamental treatment for patients with end‐stage hepatic failure. In order to perform living‐donor liver transplantations under safer conditions, apheresis plays a major role in Japan due to the prevalence of living‐donor liver transplantation wherein later retransplantation is difficult. In our department, the roles of apheresis in liver transplantation are as follows: as bridge therapy to liver transplantation (n = 45); as a supplement to the graft liver until the recovery of hepatic function (n = 77); as treatment for multiple organ failure including posttransplantation renal failure (n = 15); and as a means with which to reduce antibody titers for antibodies such as anti‐A or anti‐B in persons with ABO blood type = incompatible liver transplantation (n = 23). In our department, we have performed 822 liver transplantations at present. Of those cases, 183 were selected wherein apheresis was performed around the time of the operation. In all cases, transplantation with sufficient apheresis was performed before the surgical operation, however, 22 patients (48.9%) died after undergoing surgery. Among the patients who underwent the postoperative apheresis, those in the nonsurvivor group had lower grafted liver weights compared to those of the survivor group. The kidney was the organ that most frequently failed due to postoperative complications. In cases of ABO blood type‐incompatible liver transplantations, patients with high preoperative anti‐A/B IgM antibody titers sustained bile duct complications, patients with high preoperative anti‐IgG antibody titers sustained hepatic necrosis, and patients with high postoperative anti‐A/B IgM and anti‐IgG antibody titers sustained hepatic necrosis most frequently.     

Advantages of thoracoabdominal approach by oblique incision for right-side hepatectomy

BACKGROUND/AIMS: Thoracoabdominal approach might be safe and facilitate hepatic resection for tumors located in the right lobe. To evaluate the clinical usefulness of the thoracoabdominal approach using oblique incision for the right-side hepatectomy, we compared the perioperative data with those of the abdominal approach. METHODOLOGY: The oblique incision for the thoracoabdominal approach was placed along the intercostal space (Oblique group, n=13). The J-shape incision for abdominal approach consisted of an upper median incision and transverse incision (J-shape group, n=13). RESULTS: Patient demographics were similar in the two groups. Operation time was significantly shorter in the oblique group (292 +/- 122 min) than in the J-shape group (450 +/- 137 min, p < 0.01). The difference was noted regardless of the extent of hepatic resection. Clamping time and blood loss were similar in the two groups. The postoperative period of use of analgesia tended to be shorter in the oblique group (9 +/- 3 days) than in the J-shape group (15 +/- 11 days) but not significant (p = 0.08). Postoperative liver function tests, complications and clinical outcome were not significantly different between the two groups. CONCLUSIONS: Thoracoabdominal approach using oblique incision was useful for resection of liver tumors located in the hepatic dome and posterior segment.     

Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system.

AIMS: We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group, which had the same size liver but no PL. METHODS: The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays and the hepatic ATP level was measured. RESULTS: The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, P < 0.05). Gene expression of cyclin D1, proliferating cell nuclear antigen, cyclin A and B was upregulated, and the cyclin-dependent kinase inhibitor was downregulated. Increases were observed in: (i) pyruvate dehydrogenase, the tricarboxylic acid cycle cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48 +/- 0.01 micromol/ml vs. 0.33 +/- 0.01 micromol/ml, P < 0.05). CONCLUSION: The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism.     

Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats

BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H_2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H_2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH_2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.     

大鼠部分肝切除后肝细胞生长因子激活因子抑制因子1,2的表达

目的探讨肝细胞生长因子激活因子抑制因子(hepatocyte growth factor activator inhibitor,HAI)1、HAI-2在部分肝切除后的表达特点,分析HAI-1和HAI-2在肝再生中的作用。方法随机将健康雄性SD大鼠分成对照组和肝切除组,各30只。在肝切除手术前和手术后3 h、12 h、24 h以及48 h时,对比2组HAI-1和HAI-2 mRNA和蛋白的表达变化。结果手术前2组HAI-1、HAI-2的mRNA及蛋白均呈显著低表达,组间无明显差异(P0.05);与手术前相比,术后对照组HAI-1、HAI-2的mRNA及蛋白均无明显变化(P0.05);而肝切除组HAI-1 mRNA和蛋白表达水平先显著升高再逐渐下降,同时间点与对照组比较,差异均有统计学意义(P0.05);HAI-2 mRNA和蛋白则无明显变化(P0.05)。结论 HAI-1在部分肝切除肝细胞再生过程中呈持续高表达,其可能参与了肝细胞再生过程,而HAI-2对肝再生过程无明显影响。     

Enhancement of Liver Regeneration by the Association of Hyptis pectinata with Laser Therapy

Since new molecules that normally would accelerate regeneration can also be potentialized by light, the use of new substances combined with laser therapy seems to be a natural type of experiment. Therefore, the purpose of this study was to assess the effects of Hyptis pectinata leaves on liver regeneration after partial hepatectomy (PH) associated with laser therapy. Twenty-four rats were divided into four groups—PH(control), PHL (laser therapy), PH200 (200 mg/kg of Hyptis pectinata), and PHL200 (200 mg/kg of the plant and laser)—which were submitted to 67% hepatectomy. Laser treatment consisted of focusing the light on the remaining liver after hepatectomy. The data analyzed were serum levels of aminotransferases, liver regeneration, and mitochondrial function. Group PH200 showed a statistically significant decrease in AST levels, and PHL200 disclosed an augmentation in ALT levels. The liver regeneration index was significantly increased in group PHL200. Concerning liver mitochondrial respiratory assay, groups PH200 and PHL200 showed lower state 3 levels than groups PH and PHL. Group PHL showed an increase in state 4 levels and a reduction in membrane potential and RCR. The present study shows that the association of the aqueous extract of Hyptis pectinata leaves at 200 mg/kg with intraoperative laser therapy can stimulate liver regeneration and cause a reduction in liver mitochondrial respiratory function without altering its phosphorylative activity.     

Liver hanging maneuver decreases blood loss and operative time in a right-side hepatectomy

Background/Aims: To clarify the clinical benefits of the maneuver in right-side hepatectomy. Methodology: Eighty-one patients with liver tumor (54 hepatocellular carcinoma, 17 metastatic liver tumor and 10 other tumors) treated with a right-side hepatectomy were prospectively analyzed. The patients were divided into the following three groups: a conventional approach (group A, n=21); liver dissection under the hanging maneuver after liver mobilization (group B, n=19) and liver dissection under the hanging maneuver prior to liver mobilization (group C, n=41). Results: The liver hanging maneuver was safely performed in all the patients in groups B and C. Tumor size had a significantly positive correlation with the amount of intraoperative blood loss (R=0.52, p<0.05) in group A only. The patients in groups B and C had a significantly lower intraoperative use of blood loss (both p<0.01), operation time (p<0.05 and p<0.01) and the frequency of blood product (both p<0.05), in comparison to group A, respectively. The postoperative morbidity and the mortality rates were similar in the three groups. Conclusions: Liver hanging maneuver is a safe procedure, which can decrease intraoperative blood loss and administration of blood product in right-side hepatectomy.     

Tumor necrosis factor-alpha levels in patients with HIV with wasting in South Asia

Tumor necrosis factor (TNF)-alpha is thought to play an important role in wasting; but TNF-alpha levels have not been consistently found to be high in AIDS wasting. We conducted this study to determine any correlation between TNF-alpha levels and wasting in HIV-positive patients in a developing country. TNF-alpha levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative patients with tuberculosis with wasting (n = 25); and group 4, healthy controls (n = 25). Wasting was defined as a body bass index (BMI) 相似文献   

Relationship of glucose intolerance and indocyanine green clearance to respiratory enzyme levels in human cirrhotic liver

The relationship of glucose intolerance and indocyanine green clearance to respiratory enzyme levels in liver mitochondria was studied along with standard liver function tests in 40 patients (8 cirrhosis, 19 cirrhosis with hepatoma, 13 non-cirrhotic with hepatoma). There was a negative correlation between cytochrome a(+a3) concentrations and phosphorylative activity per unit of cytochrome a(+a3) (r = -0.75, p less than 0.01), but no correlation between ICG-K and cytochrome a(+a3) concentrations. Cytochrome a(+a3) concentrations in cirrhotic patients with linear oral glucose tolerance pattern, characterized with no return toward normal glucose levels within 120 minutes after an oral glucose load, increased to 1.45 +/- 0.11 (10(-10) mol/mg of protein) compared with 0.90 +/- 0.07 in cirrhotic patients with parabolic OGTT pattern, characterized with a return toward normal glucose levels within 120 minutes (p less than 0.01) (0.82 +/- 0.02 in control patients without liver diseases). The former had high operative mortality regardless of ICG-K value and the latter had virtually uneventful clinical courses. It was suggested that increased cytochrome a(+a3) concentrations and impaired glucose tolerance might be responsible for decreased hepatic functional reserve and poor prognosis in cirrhotics.