Fibrinolysis and fibrinogenolysis in liver disease

Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin-antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.     

Disseminated intravascular coagulation in liver cirrhosis

We measured thrombin-antithrombin III complex (TAT), soluble fibrin (SF) and D-dimer levels in 51 patients with liver cirrhosis to determine whether these tests provide new evidence for the presence of disseminated intravascular coagulation (DIC) in liver cirrhosis. TAT levels (median, range) were increased in the patient group (4.2 micrograms/l, 1.8-60.0) compared to the reference group (2.0 micrograms/l, range 1.5-7.6 micrograms/l). SF levels (0 nmol/l, range 0-80 nmol/l) were also increased in the patients as compared to the controls (0 nmol/l, 0), but there was no correlation between TAT and SF levels (r = 0.23, p less than 0.98). TAT levels did not correlate with AT-III levels (r = -0.36, p less than 0.49), but there was an inverse correlation between SF and AT-III (r = 0.60, p less than 0.001). If AT-III levels were above 0.30 U/ml, SF levels remained low, whereas SF levels were increased in patients with AT-III levels below 0.30 U/ml. These findings suggest that if sufficient AT-III is present, thrombin formation is adequately controlled, whereas at low levels of AT-III, thrombin escapes inactivation by AT-III and may act upon fibrinogen, leading to the formation of SF and a low-grade DIC. SF levels correlated well with D-dimer levels (r = 0.55, p less than 0.001), which is consistent with DIC and secondary fibrinolysis. In conclusion: (1) thrombin formation is increased in liver cirrhosis, as indicated by increased TAT levels in 21 of 51 patients; (2) the plasma concentration of AT-III appears to be of major importance for the development of DIC. The present study provides evidence for DIC in severe liver cirrhosis when AT-III levels are less than 0.30 U/ml.     

Benign bile duct tumours, non-parasitic liver cysts and liver damage in males

Pathogenetic associations between benign hepatic tumours and liver damage were studied in an autopsy series of 91 males with high incidence of alcoholism. Information on the consumption of alcohol was obtained by interviewing a family member or a close friend of the deceased. The reported use of alcohol correlated well with the increase of fatty and fibrotic changes and with the occurrence of liver cirrhosis, alcoholic hepatitis or pancreatitis. Benign bile duct tumours (bile duct adenomas and von Meyenburg's complexes) (n = 26) were associated with the occurrence of bridging (P less than 0.0005) and periportal (P less than 0.025) fibrosis of the liver and, independently from these, with chronic pancreatitis (P less than 0.05) and with non-parasitic liver cysts (n = 14) (P less than 0.01). The weight of the liver was greater (P less than 0.01) in males with focal nodular hyperplasia (n = 3). Cavernous hemangioma (n = 19) occurred independently of the parameters studied. None of the tumours showed significant correlation to liver cirrhosis, alcoholic hepatitis, fatty liver or diseases of the gallbladder. The results are in line with observations on the reactive nature and connections to fibropolycystic liver disease of benign bile duct tumours in laboratory animals and in man. Their presence in human liver specimens should be taken into account as a sign of liver damage, in this study related to heavy use of alcohol or to chronic inflammation of the pancreas.     

慢性乙型肝炎患者外周血淋巴细胞亚群与病程相关性的研究

目的对慢性乙型肝炎轻中度、重度和肝硬化患者外周血淋巴细胞亚群的百分比和绝对细胞数进行观察,探讨慢性乙型肝炎患者外周血淋巴细胞亚群的变化与病程的关系.方法采集88例慢性乙型肝炎患者柠檬酸钠新鲜抗凝血,经流式细胞仪进行免疫分型检测.结果慢性乙型肝炎重度患者的CD3+CD4+细胞百分比显著低于轻中度患者(P＜0.05),肝硬化患者的CD3+和CD3+CD8+细胞百分比显著低于轻中度患者(P＜0.01).肝硬化患者CD3CD19+细胞百分比显著高于重度和轻中度患者(P＜0.01).CD4/CD8比例在慢性乙型肝炎轻中度、重度和肝硬化患者间无显著差异.肝硬化和重度患者淋巴细胞、CD3+、CD3+CD4+、CD3+CD8+细胞的绝对细胞数均显著低于轻中度患者(P＜0.01),且肝硬化患者CD3-CD16+56+细胞的绝对细胞数显著低于轻中度患者(P＜0.05).肝硬化患者与轻中度患者的DNA载量分布差异有显著性(P＜0.01),其高水平病毒载量的患者比例高于轻中度患者.结论慢性乙型肝炎轻中度发展为重度和肝硬化的过程中,外周血淋巴细胞亚群绝对细胞数随病情的进展显著减少,主要表现为CD3+CD4+和CD3+CD8+的T淋巴细胞亚群的百分比进行性降低.     

Clinical significance of thrombin-antithrombin III complex and plasmin-alpha 2 plasmin inhibitor complex in chronic liver diseases

Thrombin-antithrombin III complex (TAT) and Plasmin-alpha 2 plasmin inhibitor complex (PIC) were examined in fifty two cases of various chronic liver diseases. TAT was significantly elevated in cases of hepatocellular carcinoma (HCC), but PIC did not show significant changes in any chronic liver diseases. Elevations of TAT and PIC were seen in cases of HCC accompanied by tumor enlargement and extensive tumor thrombosis. In cases of HCC undergoing transcatheter arterial embolization (TAE), TAT and PIC increased on the next day after TAE, and tended to recover with time, returning to almost normal at fourth week. Prolongation of prothrombin time, elevation of FDP and positive FM test were noted more often in liver cirrhosis with disseminated intravascular coagulation (DIC) than in severe liver dysfunction without DIC. Of five cases confirmed as DIC, only three cases were diagnosed as DIC by DIC score. On the other hand, TAT and PIC were significantly elevated in DIC cases. Especially, TAT exceeded 30 ng/ml in all DIC cases. TAT was regarded to be useful for the diagnosis of DIC in severe liver dysfunction.     

Portalsystemic hemodynamic changes in chronic severe hepatitis B： An ultrasonographic study

AIM： To evaluate portalsystemic hemodynamic changes in chronic severe hepatitis B.
METHODS： Hemodynamic parameters included portal vein diameter （PVD）, portal vein peak velocity （PVPV）, portal vein volume （PW）, spleen length （SPL）, spleen vein diameter （SPVD）, spleen vein volume （SPW） and umbilical vein recanalization. They were measured by Color Doppler ultrasonography in 36 patients with chronic severe hepatitis B, compared with 51 normal controls, 61 patients with chronic hepatitis B, 46 patients with compensable cirrhosis, and 36 patients with decompensable cirrhosis.
RESULTS： In the group of chronic severe hepatitis B, PVD （12.38 ± 1.23 mm） was significantly different from the normal control, compensable cirrhosis and decompensable cirrhosis groups （P = 0.000-0.026）, but not significantly different from the chronic hepatitis group. PVPV （16.15 ± 3.82 cm/s） dropped more significantly in the chronic severe hepatitis B group than the normal control, chronic hepatitis B and compensable cirrhosis groups （P = 0.000-0.011）. PW （667.53 ± 192.83 mL/min） dropped significantly as compared with the four comparison groups （P = 0.000-0.004）. SPL （120.42 ± 18.36 mm） and SPVD （7.52 ± 1.52 mm） were longer in the normal control and chronic hepatitis B groups （P = 0.000-0.009）, yet they were significantly shorter than those in the decompensable cirrhosis group （P = 0.000）. SPW （242.51 ± 137.70 mL/min） was also lower than the decompensable cirrhosis group （P = 0.000）. The umbilical vein recanalization rate （75%） was higher than the chronic hepatitis B and compensable cirrhosis groups. In the course of progression from chronic hepatitis to decompensable cirrhosis, PVD, SPL and SPVD gradually increased and showed significant differences between every two groups （P = 0.000-0.002）.
CONCLUSION： Patients with chronic severe hepatitis B have a tendency to develop acute portal hypertension, resulting in significantly reduced portal vein     

慢性乙型肝炎患者凝血功能和血小板参数检测结果分析

目的探索慢性乙型肝炎患者凝血功能和血小板参数变化的临床意义。方法收集慢性肝炎重度42例、慢加急肝衰竭24例、慢性肝衰竭35例、肝硬化32例和健康人群50例,检测血小板参数（PLT、MPV、PDW、P-LCR）和凝血功能指标（PT、APTT、TT、Fig）。结果与对照组比,各型慢性肝炎组MPV、PDW、P-LCR升高,PLT降低（P〈0.01）;慢加急肝衰竭、慢性肝衰竭和肝硬化组MPV、PDW、P-LCR高于慢性肝炎重度组,PLT低于慢性肝炎重度组（P〈0.01）;慢加急肝衰竭组PLT、MPV、PDW和慢性肝衰竭组MPV高于肝硬化组（P〈0.05,P〈0.01）;慢加急肝衰竭组与慢性肝衰竭组PLT差异有统计学意义（P〈0.01）;与对照组比较,各型慢性肝炎组PT、APTT、TT升高,Fig降低（P〈0.01）;慢加急肝衰竭组、慢性肝衰竭组、肝硬化组PT、APTT、TT高于慢性肝炎重度组（P〈0.01）,Fig低于慢性肝炎重度组（P〈0.01）;慢加急肝衰竭组和慢性肝衰竭组Fig低于肝硬化组,慢性肝衰竭组APTT高于肝硬化组（P〈0.01）;慢加急肝衰竭组与慢性肝衰竭组APTT差异有非常显著性意义（P〈0.01）。结论凝血功能和血小板参数反映了患者肝脏损害程度和出血倾向。     

Decreased interleukin-2 receptor β chain expression by peripheral blood lymphocytes in chronic liver disease

To investigate the decrease in natural killer (NK) activity in chronic liver disease, interleukin-2 receptor beta chain (IL-2R beta) expression was assessed by peripheral blood lymphocytes (PBL) using flow cytometry and an IL-2R beta chain-specific mouse monoclonal antibody. The percentage of IL-2R beta chain-positive PBL was significantly decreased in patients with chronic viral hepatitis, liver cirrhosis and hepatocellular carcinoma in comparison with normal controls (P less than 0.01). Among chronic viral hepatitis patients, it was significantly less in those with chronic active hepatitis than in those with chronic persistent hepatitis (P less than 0.05). Two-colour flow cytometry revealed that the IL-2R beta chain was mainly expressed by CD8+ or CD16+ cells in both the controls and the liver disease patients. CD8dull+ cells (NK cells) constituted more than 60% of the CD8+ cells expressing the IL-2R beta chain. Expression of the IL-2R beta chain with CD8 or CD16 was also significantly decreased in chronic liver disease patients compared with controls. In chronic viral hepatitis, there was a significant correlation between NK activity and the percentage of IL-2R beta+ PBL (P less than 0.001, r = 0.916), as well as between NK activity and the percentage of PBL co-expressing both the IL-2R beta chain and CD16 (P less than 0.001, r = 0.850). These findings suggest that decreased expression of the IL-2R beta chain by PBL may result in diminished NK activity in chronic liver disease.     

Thrombin and plasmin generation in patients with liver disease

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.     

High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease.

OBJECTIVE: To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients. DESIGN: Cross-sectional study. SETTING: A referral-based university hospital. PATIENTS: Consecutive patients (164) with the Pi ZZ and Pi Z phenotype with and without chronic liver disease. MEASUREMENTS: The presence of antibody to hepatitis C virus (anti-HCV) was determined using an assay incorporating synthetic peptide antigen from capsid protein (United Biomedical [UBI] assay) and a second-generation enzyme immunoassay (Abbott test); the presence of antibody to hepatitis B virus (anti-HBV) was determined using radioimmunoassays incorporating hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg); assays for antinuclear antibody and antimitochondrial antibody (M2 subtype) were also done, and alcohol abuse was assessed by history. RESULTS: Among patients with cirrhosis (32%), 62% were anti-HCV positive by the Abbott test (P = 0.006), and 41% were anti-HCV positive by the UBI assay (P = 0.007). Thirty-three percent of patients with cirrhosis had hepatitis B virus (HBV) infection (P = 0.01); 41% had a history of alcoholism; and 12% had features of autoimmune liver disease. Only five patients (9%) with cirrhosis had no other risk factor for chronic liver disease. Among patients with chronic active hepatitis (7%), 80% were anti-HCV positive by the Abbott test (P = 0.002), and 75% were anti-HCV positive by the UBI assay (P less than 0.001). Thirty percent of patients with chronic active hepatitis had HBV infection (P = 0.023); 18% had autoimmune hepatitis; and 8% abused alcohol. Only two patients (17%) had no additional risk factor for the development of chronic active hepatitis. Among patients with steatosis of the liver (48%), 5% were anti-HCV positive by the Abbott test, and none were anti-HCV positive by the UBI assay; 18% had serologic evidence of past HBV infection, and 28% abused alcohol. Among patients without chronic liver disease (13%), no viral infection could be found; 9% were alcoholics. CONCLUSIONS: Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients.     

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients

AIM： To study and determine the resting energy ex- penditure （REE） and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS： A total of 100 patients with liver diseases were categorized into three groups： 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were as- sessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS： The REE of the severe chronic hepatitis group （20.7 ± 6.1 kcal/d per kg） was significantly lower than that of the acute hepatitis group （P = 0.014）. The respiratory quotient （RQ） of the severe chronic hepatitis group （0.84 ± 0.06） was significantly lower than that of the acute hepatitis and cirrhosis groups （P = 0.001）. The glucose oxidation rate of the severe hepatitis group （39.2%） was significantly lower than that of the acute hepatitis group and the cirrhosis group （P 〈 0.05）, while the fat oxidation rate （39.8%） in the severe hepatitis group was markedly higher than that of the other two groups （P 〈 0.05）. With improve- ment of liver function, the glucose oxidation rate in- creased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION： The glucose oxidation rate is signifi-cantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These re- sults warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.     

肝病伴糖代谢异常患者的临床分析

目的探讨肝病伴糖代谢异常的临床特点及其可能机制.方法分别对29例慢性乙型肝炎伴糖代谢异常患者及62例乙型肝炎后肝硬化伴糖代谢异常患者进行相关分析.结果 （1）乙型肝炎后肝硬化患者中肝源性糖耐量减低（IGT）及肝源性糖尿病（DM）发生率高于慢性乙型肝炎患者（20.53%对3.82%,P＜0.05;24.11%对1.64%,P＜0.01）.（2）慢性乙型肝炎及乙型肝炎后肝硬化伴肝源性IGT或DM患者均无糖尿病症状,而19例慢性乙型肝炎伴原发性DM者中12例有症状,12例乙型肝炎后肝硬化伴原发性DM者中6例有症状.（3）慢性乙型肝炎伴肝源性IGT或DM者,空腹血糖（FPG）、餐后血糖（PPG）水平均低于伴原发性DM者（P＜0.05）;但前者葡萄糖负荷后胰岛素（PINS）及C肽（PCP）分泌水平高于后者（P＜0.05）.（4）乙型肝炎后肝硬化伴肝源性DM与伴原发性DM患者的FPG、PPG水平差异均无统计学意义,伴肝源性DM患者空腹胰岛素（FINS）、PINS、空腹C肽（FCP）及PCP水平高于伴原发性DM患者（P＜0.05）,但两者的PINS/FINS、PCP/FCP值差异无统计学意义,且小于5;伴肝源性DM患者其FPG、PPG水平均显著高于伴肝源性IGT者（P＜0.05）,FINS、PINS及FCP、PCP水平均低于肝源性IGT患者（P＜0.05,P＜0.01）.结论肝病继发糖代谢异常者多发生于肝硬化患者,且以肝功能损害较重者为主,多无症状;慢性乙型肝炎伴肝源性DM患者胰岛β细胞分泌胰岛素的功能增强,而乙型肝炎后肝硬化伴肝源性DM患者则减弱.     

Anti-Hepatitis C Antibodies in Patients with Chronic Non-A, Non-B Hepatitis: Relation to Disease Progression and Effect of Interferon α

The activity of antibodies to hepatitis C virus (anti-HCV) was investigated in 80 patients with chronic non-A, non-B liver diseases. Serum anti-HCV titer was determined by the "Ortho-HCV" enzyme-linked immunosorbent assay with some modifications to quantify the activity. Anti-HCV was positive in 82.5% of cases (66/80). Anti-HCV occurred significantly less often in the patients with chronic persistent hepatitis (8/13, 61.5%) than in those with chronic active hepatitis (42/49, 85.7%) (p less than 0.05). Anti-HCV titer of the patients with chronic persistent hepatitis and that with chronic active hepatitis was significantly higher than that with liver cirrhosis (p less than 0.01 and p less than 0.05). There was no correlation between anti-HCV titer and histology activity index in chronic hepatitis. Serial study demonstrated that anti-HCV titer decreased more frequently in the patients who responded to IFN alpha therapy (11/22, 50.0%) than in those who did not respond to IFN alpha therapy (0/10, 0%) (p less than 0.01). These results indicate that anti-HCV level does not correlate with the activity of hepatitis, but that it decreases in accordance with the disease progression to liver cirrhosis or with the response to IFN alpha therapy.     

Serum hyaluronan--a non-invasive test for diagnosing liver cirrhosis

INTRODUCTION: Hyaluronan is a glucosaminoglycan synthesized by the mesenchymal cells and degraded by hepatic sinusoidal endothelial cells by a specific receptor-mediated process. Elevated levels are associated with the sinusoidal capillarization that is seen in cirrhosis. METHODOLOGY: Serum hyaluronan was measured, using a radiometric assay (Pharmacia, Sweden) in 221 patients with biopsy-proven chronic liver disease of a variety of aetiologies (alcohol n = 70, autoimmune chronic active hepatitis n = 23, primary biliary cirrhosis n = 17, hepatitis C n = 69, cryptogenic n = 15, various n = 27). All patients were fasted, and their liver function tests, full blood count, prothrombin time and Child-Pugh score were assessed at the time of the liver biopsy. RESULTS: Hyaluronan levels (microg/l) were significantly higher in patients with liver cirrhosis (cirrhosis n = 127, mean 440, 95% CI 367-515) (P < 0.0001) compared with hepatic fibrosis (n = 23, mean 144, 95% CI 69-190), chronic hepatitis (n = 60, mean 63, 95% CI 37-91) and fatty liver (n = 11, mean 107, 95% CI 37-177). Within the cirrhotic population, there was no significant difference in hyaluronan levels between different aetiologies, but hyaluronan level increased proportionally to the severity of cirrhosis. Overall, a hyaluronan level > 100 microg/l had a 78% specificity and 83% sensitivity for diagnosing cirrhosis, while the specificity was increased to 96% for all patients with hyaluronan levels > 300 microg/l. The highest specificity and sensitivity were seen at a cut-off value of 100 microg/l in patients with alcohol-associated liver disease (89%, 87%) and hepatitis C (93%, 72%) respectively. Within patient cohorts, there was a significant correlation (P < 0.01) between hyaluronan and albumin, platelet count and bilirubin, but not with alanine aminotransferase. CONCLUSION: Measurement of fasted serum hyaluronan reliably differentiated cirrhotic from non-cirrhotic liver disease and can be regarded as a useful test in the diagnosis of liver cirrhosis, particularly when a liver biopsy is contraindicated.     

Increased levels of fibrinolysis reaction products (D-dimer) in patients with decompensated alcoholic liver cirrhosis.

We studied the activation of coagulation and fibrinolysis in the blood of patients with compensated (n = 25) and decompensated (n = 25) liver cirrhosis. We observed increased blood concentrations of thrombin-antithrombin III (TAT) complexes (p less than 0.001) and of D-dimer (p less than 0.001) in both groups of patients compared with healthy volunteers (n = 25). The blood levels of tissue-type plasminogen activator (t-PA) activity (p less than 0.001) and the concentrations of t-PA antigen (p less than 0.001) were also significantly raised in both groups of patients compared with controls, whereas plasminogen activator inhibitor did not deviate. There were no significant differences in the determined variables between the two groups of patients except that the concentrations of D-dimer were significantly higher (p less than 0.001) in patients with decompensated liver cirrhosis. The ratio between D-dimer and TAT did not deviate between patients with compensated liver cirrhosis and healthy volunteers but was significantly increased in patients with decompensated liver cirrhosis. These observations indicate that efflux from the extravascular space (for example, ascitic fluid) contributes to the high concentrations of fibrin degradation products (D-dimer) in patients with decompensated liver cirrhosis. In addition, we conclude that patients with liver cirrhosis have an enhanced activation of both coagulation and fibrinolysis but that the balance between these two systems is not significantly displaced compared with healthy volunteers.     

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.     

Wedged hepatic venous pressure recording and venography for the assessment of pre-cirrhotic and cirrhotic liver disease

Wedged hepatic venous pressure recording and venography were investigated to assess histologic reflection of the stage of chronic liver disease. Forty-nine patients were studied. The four main groups and the means of the pressure gradients (WHVP - FHVP) with their 95% confidence limits were chronic active hepatitis (n = 12), 6 mm Hg (4.35-7.65); chronic hepatitis in transition to cirrhosis (n = 9), 10.3 mm Hg (6.6-14.1); and established cirrhosis (n = 8), 15.4 mm Hg (9.4-21.4); but only 3.4 mm Hg (2.2-4.6) in near-normal liver (n = 8). A pressure gradient of more than 5 mm Hg was always associated with significant liver disease on liver biopsy. In 25 patients venographies were assessed. Whereas patients with near-normal biopsy specimens had normal appearances, patients with more severe disease showed increasingly severe changes. The techniques applied should not replace liver biopsy. However, they provide relevant supplementary information, might have a place in follow-up studies to assess progression of disease, and occasionally reduce the need for liver biopsy.     

Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis

Diabetes mellitus has been reported to have an increased prevalence and to be associated with more severe fibrosis in patients with chronic hepatitis C. We evaluated the prevalence of diabetes mellitus in patients with chronic hepatitis B or C as well as the possible association between presence of diabetes and extent of liver fibrosis. In total, 434 consecutive patients with histologically documented hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (n = 174) or chronic hepatitis C (n = 260) were studied. The relationships of diabetes and epidemiological, somatomorphic, laboratory and histological patient characteristics were evaluated. Liver histological lesions were blindly evaluated according to the Ishak's classification. Diabetes was present in 58 (13%) patients, without any difference between those with chronic hepatitis B (14%) or C (13%). Diabetes was observed significantly less frequently in patients with fibrosis score 0-2 (7.7%) than 3-4 (10.4%) than 5-6 (29.2%) (P < 0.001). The presence of diabetes was independently associated with higher gamma-glutamyl-transpeptidase (GGT) levels and more severe fibrosis or presence of cirrhosis (P < 0.001) as well as with presence of hepatic steatosis and increased serum triglycerides levels (P < 0.02). In the noncirrhotic patients, diabetes was significantly associated with older age and higher GGT levels, but not with the extent of fibrosis. In conclusion, diabetes mellitus is observed in more than 10% of patients with either HBeAg-negative chronic hepatitis B or chronic hepatitis C. The presence of diabetes is strongly associated with more severe liver fibrosis, but such an association may be related to the high prevalence of diabetes in patients with cirrhosis.     

葡萄糖激酶mRNA、葡萄糖转运蛋白2在慢性乙型重型肝炎患者糖代谢异常中的作用

目的通过研究葡萄糖激酶（GCK）mRNA、葡萄糖转运蛋白2（GLUT2）在慢性乙型重型肝炎（慢重肝）患者肝组织中的表达来初步探讨其在慢重肝糖代谢异常中的作用。方法运用RT-PCR法测定10例慢重肝患者和10例肝硬化（CTP评分A级）患者肝脏GCK mRNA的表达;免疫组织化学方法检测上述10例慢重肝患者及10例正常对照肝组织GLUT2表达。两组间均数比较采用t检验,相关性采用Pearson相关分析。结果慢重肝肝组织GCK mRNA表达低于肝硬化组,（1.13±0.11）vs（1.44±0.14）,P〈0.05。慢重肝肝组织GCK mRNA水平与碳水化合物氧化率呈正相关（r=0.845,P〈0.01）,与空腹血糖无明显相关性（r=0.03,P〉0.05）。慢重肝肝组织GLUT2表达减少,且分布在假小叶结节周围细胞。结论肝脏GCK mRNA水平与糖氧化利用密切相关,GCK mRNA与GLUT2表达减少是慢重肝糖代谢障碍发生的机制之一。     

Free testosterone index: comparison with plasma free testosterone

Blood-free testosterone indices were measured among 28 normal men (age; 24-48 yrs.), 20 normal women (20-36 yrs.), 18 pregnant women (22-31 yrs.), 17 males with hypogonadism (23-56 yrs.), 17 males with chronic hepatitis (20-42 yrs.), 24 males with liver cirrhosis (29-68 yrs.), 34 males with hyperthyroidism (20-42 yrs.) and 7 hirsute women (18-31 yrs.), and these were compared with the plasma concentrations of free testosterone. The testosterone index was obtained by multiplying the plasma concentration of testosterone by the percent of sex hormone-binding globulin (SHBG), non-bound testosterone precipitated by dextran-coated charcoal. A significant increase of plasma testosterone was observed in patients with chronic hepatitis (p less than 0.001) and hyperthyroidism (p less than 0.001) as compared with normal men and was also observed in pregnant (p less than 0.01) and hirsute women (p less than 0.01) as compared with normal women. The close negative correlation between plasma levels of testosterone and the percent of SHBG non-bound testosterone (r = -0.87, n = 79, p less than 0.001) was observed among normal men, male patients with chronic hepatitis and hyperthyroidism. The sex hormone binding capacity was increased from two to three fold in patients with chronic hepatitis and hyperthyroidism. The patients with compensated liver cirrhosis had increased plasma testosterone and a decreased percent of SHBG non-bound testosterone, and those with decompensated liver cirrhosis had decreased plasma testosterone and a normal percent of SHBG non-bound testosterone. The plasma concentration of free testosterone was normal in patients with chronic hepatitis and hyperthyroidism. It decreased in pregnancy (p less than 0.01) and increased in hirsute women (p less than 0.01). The blood free testosterone index was slightly high in one third of the patients with chronic hepatitis and hyperthyroidism as compared with that in normal men. However, a close correlation of the percent of SHBG non-bound testosterone and fractional free testosterone (%) measured by equilibrium dialysis (gamma = 0.82, p less than 0.001) was obtained in all subjects (n = 170). These data suggest that the blood free testosterone index parallels the plasma concentration of free testosterone and is useful to evaluate the status of androgenicity.