Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis

BackgroundThe knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients.AimTo describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis.MethodsThe patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded.ResultsAt presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p < 0.0001) and the incidence of first variceal bleeding (p = 0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p = 0.02).ConclusionsIn the patients with non-cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients.     

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: is it an Immuno-Inflammatory Disorder?

Background and aimsPortal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients.Material and methodsA total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry.ResultsCompared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641-0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each.ConclusionEnhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.     

Relationship between levels of DNA damage in lymphocytes and histopathological severity of chronic hepatitis C and various clinical forms of hepatitis B

BACKGROUND AND AIM: A significant proportion of cancer is attributable to DNA damage caused by chronic infection and inflammation. Because both hepatitis B and C viruses (HBV and HCV, respectively) cause chronic infection and inflammatory disease, the aim of the present study was to investigate whether there is a difference in peripheral DNA damage in patients with chronic HCV compared with patients with chronic HBV; and whether there is an association in the level of peripheral DNA damage with a natural history of HBV infection. METHODS: Twenty patients with chronic hepatitis C, 20 patients with chronic hepatitis B, 11 patients with cirrhosis secondary to hepatitis B, 12 inactive hepatitis B s antigen (HBsAg) carriers and 21 healthy subjects were included in the study. The DNA damage in lymphocytes was determined using the alkaline comet assay. RESULTS: Although the chronic hepatitis C group had similar levels of DNA damage compared with patients with cirrhosis due to hepatitis B (P > 0.05) and non-cirrhotic patients with chronic hepatitis B (P > 0.05), they had higher levels of DNA damage compared with inactive HBsAg carriers (P = 0.021) and controls (P = 0.001). Hepatitis B cirrhotic patients and patients with chronic hepatitis B had significantly higher levels of DNA damage than inactive HBsAg carriers (P = 0.002 and P = 0.012, respectively) and controls (both P = 0.001). Linear logistic regression analysis showed that chronic hepatitis C and HBV-related cirrhosis were discriminators in determining DNA damage in lymphocytes (beta 0.424 and P = 0.013, beta 0.393 and P = 0.016, respectively). CONCLUSIONS: Chronic hepatitis C, based on the severity of liver disease, or cirrhosis as an advanced form of HBV infection increase DNA damage in lymphocytes independently of confounding factors such as age, gender, body mass index and smoking habits.     

Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity

AIM： To evaluate serum neopterin levels and their correlations with liver function tests and histological grade in children with hepatitis-B-related chronic liver disease. METHODS： The study population comprised 48 patients with chronic active hepatitis B, 32 patients with hepatitis-B-related active liver cirrhosis and 40 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay. RESULTS： The mean ＋ SD serum neopterin levels were 14.2 ± 5.6 nmol/L in patients with chronic hepatitis, 20.3 ± 7.9 nmol/L in patients with liver cirrhosis and 5.2 ± 1.4 nmol/L in control group. Serum neopterin levels were significantly higher in patients with chronic hepatitis （P = 0.005） and cirrhosis patients （P = 0.008）, than in control subjects. Cirrhotic patients had significantly higher serum neopterin levels than patients with chronic hepatitis （P = 0.004）. There was a positive correlation between serum neopterin levels and alanine aminotransferase levels in patients with chronic hepatitis （r = 0.41, P = 0.004） and cirrhotic patients （r = 0.39, P = 0.005）. Positive correlations were detected between serum neopterin levels and inflammatory score in patients with chronic hepatitis （r = 0.51, P = 0.003） and cirrhotic patients （r = 0.49, P = 0.001）. CONCLUSION： Our results suggest that serum neopterin levels can be considered as a marker of inflammatory activity and severity of disease in children with hepatitis-B-related chronic liver disease.     

Aspartate aminotransferase : alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis?

BACKGROUND: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST:ALT > or = 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST:ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. METHODS: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST:ALT. RESULTS: In 30 patients with cirrhosis, the mean AST:ALT (0.99 +/- 0.06) was higher than in 123 patients without cirrhosis (0.60 +/- 0.02; P < 0.001). A ratio > or = 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. CONCLUSION: Although relatively insensitive, an AST:ALT > or = 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients.     

Splanchnic and renal extraction of circulating hyaluronan in patients with alcoholic liver disease

Splanchnic and renal extraction of hyaluronan was determined in patients with alcoholic cirrhosis (n = 9), non-cirrhotic alcoholic liver disease (n = 5), and controls without liver disease (n = 19) in the supine fasting condition. Arterial plasma concentration of hyaluronan was significantly increased in patients with cirrhosis (mean 480 micrograms/l) as compared to non-cirrhotic patients (29 micrograms/l, P less than 0.001) and controls (25 micrograms/l, P less than 0.001), whereas no difference was present between the two last-mentioned groups. In patients with liver disease, circulating hyaluronan was inversely correlated to indocyanine green clearance (r = -0.85, P less than 0.001) and to galactose elimination capacity (r = -0.62, P less than 0.02), but positively correlated to portal pressure (determined as wedged-to-free hepatic vein pressure) (r = 0.92, P less than 0.001). Splanchnic extraction ratio (arterio-hepatic venous extraction ratio) had a mean value of 0.14 in patients with cirrhosis as compared to 0.36 in non-cirrhotic patients (P less than 0.05) and 0.34 in controls (P less than 0.025). Splanchnic hyaluronan extraction was not correlated to liver function tests or portal pressure. In patients with alcoholic liver disease no significant renal hyaluronan extraction was found as compared to an extraction ratio of 0.17 in controls (P less than 0.05). Our results suggest that the increased level of circulating endogenous hyaluronan found in patients with cirrhosis is caused by a combination of increased supply to and decreased extraction from plasma.     

原发性肝癌合并与不合并肝硬化患者年龄及乙型肝炎病毒血清学特点比较

目的探讨原发性肝癌（PHC）合并肝硬化与无肝硬化患者年龄及HBV血清学特点。方法回顾性分析经影像学检查及甲胎蛋白（AFP）测定诊断为PHC的患者547例,分为有肝硬化和无肝硬化两组,统计分析并比较其年龄分布及HBV血清学标记的特点。结果合并肝硬化与无肝硬化患者分别为265例及282例,两组伴HBV感染者分别为221例、256例。合并肝硬化的肝癌患者男女比例为7.83∶1;60岁以下的男性肝癌患者年龄分布无明显差异,无肝硬化的男性肝癌患者60岁以上比例明显高于有肝硬化者（P〈0.005）。合并肝硬化的男性肝癌患者HBV感染率40岁以下年龄组最高（96.67%）,而HBeAg血清学转换率以40～60岁年龄段最高（89.47%）;无肝硬化者HBV感染率40～60岁年龄段最高（90.43%）,但HBeAg血清学转换率最低（80%）。结论合并肝硬化的PHC患者中,男性占大多数,而且早年HBV感染率高;无肝硬化的PHC患者中,老年人占多数;HBeAg血清学转换率高的人群肝癌发病率相对较高。     

An electron microscopic and morphometric study of ursodeoxycholic effect in primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease that results in cholestasis and bile duct loss. Ursodeoxycholic acid (UDCA) has been shown to reduce hepatocellular damage in PBC. The study attempted to quantify perisinusoidal collagenization and the number of apoptotic bodies in PBC liver biopsies from patients in a randomized control trial treated with UDCA compared to those who received placebo. METHODS: Twenty-eight patients with PBC (10 cirrhotic, 18 non-cirrhotic; 13 treated with UDCA, 15 treated with placebo) were compared with 32 controls with normal hepatic histology on light microscopy. Liver biopsies were examined for degree of perisinusoidal fibrosis and apoptotic activity using electron microscopy. RESULTS: The degree of perisinusoidal fibrosis and apoptotic activity was similar in pretreatment biopsies of UDCA and placebo-treated patients. After two years of placebo, patients showed a significant increase in fibrosis (P < 0.001). In contrast, there were no changes in non-cirrhotic and a decrease in fibrosis in cirrhotic patients given UDCA. At baseline, PBC patients had higher numbers (apoptotic cells/100 hepatocytes +/- SE) of apoptotic cells (7 +/- 3), than controls (2 +/- 0.5) (P < 0.05), with no difference between cirrhotic and non-cirrhotic patients in the two groups of patients. After two years, the numbers of apoptotic cells in UDCA-treated patients decreased significantly compared to baseline (3 +/- 2) (P < 0.05); with placebo patients the number of apoptotic cells increased (12 +/- 5) (P < 0.05). CONCLUSION: Treatment with UDCA prevents the deposition of perisinusoidal collagen and reduces the apoptotic activity in PBC patients after 2 years of therapy.     

Oxidative stress in chronic hepatitis C: not just a feature of late stage disease

BACKGROUND/AIMS: Chronic hepatitis C infection is a major world-wide problem, frequently progressing to cirrhosis, liver failure or hepatoma. The pathological mechanisms of disease progression are unclear but oxidant stress may play a role.METHODS: Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood or urine from 42 chronic hepatitis C patients. Fibrosis was graded histologically in a subgroup of 33 patients.RESULTS: The lipid peroxidation marker 8-isoprostane and the ratio of oxidized to reduced glutathione were significantly elevated (P<0.001, P=0.006). The antioxidants glutathione, selenium and vitamins A, C and E were significantly decreased (all P<0.001) compared to age and sex matched controls. Abnormal values were more marked in cirrhotics, but significant changes were also observed in the non-cirrhotic group. The fibrosis score correlated positively with urinary 8-isoprostane and type III procollagen peptide and negatively with vitamin A.CONCLUSIONS: Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of hepatitis C infection. Although more severe in the cirrhotic group, there was clear evidence of oxidant stress in non-cirrhotic patients. Antioxidant therapy may therefore have a role in slowing disease progression to cirrhosis.     

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.RESULTS The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 28.4%, P 0.001) and mortality rate(21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012), alcohol consumption(OR: 6.4, P = 0.020), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.     

Changes in distribution of splenic venous flow in the patients with cirrhotic liver

BACKGROUND/AIMS: The aim of this study is to prove the hemodynamic change in distribution of splenic venous flow in the liver, especially in the cirrhotic liver, and to reveal and evaluate a participation of splenic venous flow in regeneration or enlargement of the hepatic lobe. METHODOLOGY: We studied the distribution of splenic venous flow in the liver of patients with normal liver (NL group, n=15), chronic hepatitis (CH group, n=8), and liver cirrhosis (LC group, n=13) with the technique of scintiphotosplenoportography after percutaneous intrasplenic injection of Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin. The index of splenic venous flow volume per unit hepatocytes (Vunit) was calculated in each hepatic lobe. To compare V value of the left lobe (VLunit) with that of the right lobe (VRunit), predominant index of the left lobe (L/R index) was defined as L/R index = VLunit/VRunit. RESULTS: The median (interquartile range) of L/R index of the LC group; 1.22 (1.06-1.70) was significantly higher than that of the NL group; 0.83 (0.66-0.92), p<0.001 and the CH group; 0.79 (0.69-0.92), p<0.001. CONCLUSIONS: L/R index reflects the change of portal hemodynamics in cirrhotic liver and is useful for discrimination between noncirrhosis and cirrhosis. These results suggest that in the liver exposed to continuous damages, splenic venous blood promotes liver fibrosis in the right lobe and eventually flows more into the left lobe with milder fibrosis.     

Hepatic phospholipids in alcoholic liver disease assessed by proton-decoupled 31P magnetic resonance spectroscopy

BACKGROUND/AIMS: Alteration of the phospholipid composition of hepatic biomembranes may be one mechanism of alcoholic liver disease (ALD). We applied proton-decoupled (31)P magnetic resonance spectroscopic imaging ({(1)H}-(31)P MRSI) to 40 patients with ALD and to 13 healthy controls to confirm that metabolic alterations in hepatic phospholipid intermediates could be detected non-invasively. METHODS: All patients underwent liver biopsy. Specimens were scored in non-cirrhosis [fatty liver (n=3), alcoholic hepatitis (n=2), fibrosis (n=4), alcoholic hepatitis plus fibrosis (n=16)], and cirrhosis (n=15). {(1)H}-(31)P spectra were collected on a clinical 1.5-Tesla MR system and were evaluated by calculating signal intensity ratios of hepatic phosphomonoester (PME), phosphodiester (PDE), phosphoethanolamine (PE), phosphocholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC) resonances. RESULTS: The signal intensity ratio GPE/GPC was significantly elevated in cirrhotic (1.19+/-0.22; P=0.002) and non-cirrhotic ALD patients (1.01+/-0.13; P=0.006) compared to healthy controls (0.68+/-0.04), while PE/PC and PME/PDE were significantly elevated in cirrhotic ALD patients compared to controls (1.68+/-0.60 vs. 0.97+/-0.31; P=0.02, and 0.38+/-0.02 vs. 0.25+/-0.01; P=0.002, respectively) and non-cirrhotic patients. CONCLUSIONS: The data support that {(1)H}-(31)P MRSI appears to distinguish cirrhotic from non-cirrhotic ALD patients and confirms changes in hepatic phospholipid metabolism observed in an animal model.     

Impact of cirrhosis on surgical outcome after pancreaticoduodenectomy

AIM:To elucidate surgical outcomes of pancreaticoduodenectomy(PD)in patients with liver cirrhosis.METHODS:We studied retrospectively all patients who underwent PD in our centre between January 2002and December 2011.Group A comprised patients with cirrhotic livers,and Group B comprised patients with non-cirrhotic livers.The cirrhotic patients had ChildPugh classes A and B(patient’s score less than 8).Preoperative demographic data,intra-operative data and postoperative details were collected.The primary outcome measure was hospital mortality rate.Secondary outcomes analysed included duration of the operation,postoperative hospital stay,postoperative morbidity and survival rate.RESULTS:Only 67/442 patients(15.2%)had cirrhotic livers.Intraoperative blood loss and blood transfusion were significantly higher in group A(P=0.0001).The mean surgical time in group A was significantly longer than that in group B(P=0.0001).Wound complications(P=0.02),internal haemorrhage(P=0.05),pancreatic fistula(P=0.02)and hospital mortality(P=0.0001)were significantly higher in the cirrhotic patients.Postoperative stay was significantly longer in group A(P=0.03).The median survival was 19 mo in group A and 24 mo in group B.Portal hypertension(PHT)was present in 16/67 cases of cirrhosis(23.9%).The intraoperative blood loss and blood transfusion were significantly higher in patients with PHT(P=0.001).Postoperative morbidity(0.07)and hospital mortality(P=0.007)were higher in cirrhotic patients with PHT.CONCLUSION:Patients with periampullary tumours and well-compensated chronic liver disease should be routinely considered for PD at high volume centres with available expertise to manage liver cirrhosis.PD is associated with an increased risk of postoperative morbidity in patients with liver cirrhosis;therefore,it is only recommended in patients with Child A cirrhosis without portal hypertension.     

Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis

OBJECTIVE: Thrombophilic gene mutations have been reported to be associated with the formation of portal vein thrombosis (PVT). This study aimed to investigate the role of thrombophilic gene mutations in cirrhotic patients with PVT. PATIENTS AND METHODS: A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and 19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations were analysed by restriction fragment length polymorphism. RESULTS: Aetiologies and Child-Pugh distribution of cirrhotic patients with and without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A mutation (P<0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%) non-cirrhotic patient with PVT and two (2.5%) controls had this mutation (P<0.05). The frequency of the homozygote methylenetetrahydrofolate reductase 677C-T mutation was similar in all four groups. CONCLUSIONS: Inherited thrombophilic gene mutations appear to increase the risk of PVT formation in cirrhotic patients but not in patients without liver disease in a cohort of Turkish patients.     

Noninvasive assessment of liver damage in chronic hepatitis B

AIM:To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index(APRI)and neutrophillymphocyte(N/L)ratio to predict liver damage in chronic hepatitis B(CHB).METHODS:We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects.Liver biopsy materials were stained with hematoxylin-eosin and Masson’s trichrome.Patients’fibrosis scores and histological activity index(HAI)were calculated according to the Ishak scoring system.Fibrosis score was recognized as follows:F0-1 No/early-stage fibrosis,F2-6 significant fibrosis,F0-4 non-cirrhotic and F5-6 cirrhotic.Significant liver fibrosis was defined as an Ishak score of≥2.APRI and N/L ratio calculation was made by blood test results.RESULTS:The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores(P<0.001).Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count.APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients.However,this significance was not confirmed by multiple logistic regression analysis.The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01with sensitivity,specificity,positive predictive value and negative predictive value of 62%(36%-86%),74%(62%-83%),29%(13%-49%)and 92%(82%-97%),respectively.In addition,correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI(r=-0.218,P=0.041).CONCLUSION:N/L ratio was negatively correlated with HAI.APRI score may be useful to exclude cirrhosis in CHB patients.     

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

AIM： To evaluate the prevalence of metabolic syndrome （MS）, obesity and type 2 diabetes mellitus （T2DM） in a group of Mexican Mestizo patients with cryptogenic cirrhosis （CC） and to compare this group with patients with cirrhosis secondary to other causes （disease controls）. METHODS： Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis （AIH） served as disease controls. RESULTS： A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years （range, 16-87）; 83 （61.9%） patients were female; 53 （39.6%） were Child A, 65 （48.5%） Child B, and 16 （11.9%） were Child C cirrhosis. The prevalence of MS （29.1% vs 6%; P 〈 0.001）, obesity （16.4% vs 8.2%; P = 0.04） and T2DM （40% vs 22.4%; P = 0.013） was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION： The prevalence of MS, obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis （NASH） plays an under-recognized role in CC.     

Prevalence of metabolic syndrome,obesity and diabetes type 2 in cryptogenic cirrhosis

AIM: To evaluate the prevalence of metabolic syndrome (MS),obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls).METHODS: Patients with CC,diagnosed between January,1990 and April,2005,were included in a retrospective study.Patients with cirrhosis caused by chronic hepatitis C,alcohol abuse or autoimmune hepatitis (AIH) served as disease controls.RESULTS: A total of 134 patients with CC were analyzed.Disease controls consisted of 81 patients with chronic hepatitis C,33 with alcohol abuse and 20 with AJH.The median age of patients with CC was 57 years (range,16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A,65 (48.5%) Child B,and 16 (11.9%) were Child C cirrhosis.The prevalence of MS (29.1% vs 6%; P ＜ 0.001),obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013)was higher in CC patients than in disease controls.There were no differences in sex,age or liver function tests between the two groups.CONCLUSION: The prevalence of MS，obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes.Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC.     

肝硬化合并高血压患者的临床特征分析

目的分析肝硬化患者合并高血压的临床特征。方法选取2008年1月-2010年12月于中国医科大学附属第一医院住院的797例肝硬化患者,比较肝硬化患者中高血压的患病率与普通人群高血压患病率的差异,以及合并高血压和不合并高血压与肝脏功能和血清离子之间的关系。结果肝硬化患者合并高血压组的患病率为4.14%,明显低于普通人群高血压患病率(18.80%)(χ2=112.064,P0.001);肝硬化合并高血压组血清门冬氨酸氨基转移酶(64.85±57.13)U/L、碱性磷酸酶(117.30±70.47)U/L和总胆汁酸(31.29±30.72)U/L等均低于肝硬化未合并高血压组,后者分别为(92.30±135.48)U/L(t=-2.159)、(147.19±135.98)U/L(t=-2.153)和(53.50±61.10)U/L(t=-3.227)(P均0.05),而血清白蛋白(33.98±11.29)g/L则高于肝硬化未合并高血压组(31.15±7.44)g/L(t=1.991,P0.05);胆红素代谢功能、凝血功能和血清离子等比较,在两组之间差异无统计学意义。结论肝硬化患者合并高血压的患病率明显低于普通人群,合并高血压时部分肝功能损伤低于未合并高血压者,合并高血压可能延缓肝硬化进展。     

Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients

BACKGROUND Reliable biomarkers of cirrhosis, hepatocellular carcinoma(HCC), or progression of chronic liver diseases are missing. In this context, Golgi protein-73(GP73) also called Golgi phosphoprotein-2, was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells. As a result, GP73 expression was found primarily in biliary epithelial cells, with only slight detection in hepatocytes. However, in patients with acute or chronic liver diseases and especially in HCC, the expression of GP73 is significantly up-regulated in hepatocytes. So far, few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA (QUANTA Lite~? GP73, Inova Diagnostics, Inc., Research Use Only) in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa, Greece(n = 366) and Debrecen, Hungary(n = 266). Aspartate aminotransferase(AST)/Platelets(PLT) ratio index(APRI) was also calculated at the relevant time points in all patients. Two hundred and three patients had chronic hepatitis B, 183 chronic hepatitis C, 198 alcoholic liver disease, 28 autoimmune cholestatic liver diseases, 15 autoimmune hepatitis, and 5 with other liver-related disorders. The duration of follow-up was 50(57) mo [median(interquartile range)]. The development of cirrhosis, liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines. In particular, the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP) determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73( 20 units) were detected at initial evaluation in 277 out of 632 patients(43.8%). GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4% vs 51.5%, P 0.001), decompensation of cirrhosis(60.3% vs 35.5%, P 0.001), presence of HCC(18.4% vs 7.9%, P 0.001) and advanced HCC stage(52.9% vs 14.8%, P = 0.002). GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score [Area under the curve(AUC)(95%CI): 0.909(0.885-0.934) vs 0.849(0.813-0.886), P = 0.003]. Combination of GP73 with APRI improved further the accuracy(AUC: 0.925) compared to GP73(AUC: 0.909, P = 0.005) or APRI alone(AUC: 0.849, P 0.001). GP73 levels were significantly higher in HCC patients compared to non-HCC [22.5(29.2) vs 16(20.3) units, P 0.001) and positively associated with BCLC stage [stage 0: 13.9(10.8); stage A: 17.1(16.8); stage B: 19.6(22.3); stage C: 32.2(30.8); stage D: 45.3(86.6) units, P 0.001] and tumor dimensions [very early: 13.9(10.8); intermediate: 19.6(18.4); advanced: 29.1(33.6) units, P = 0.004]. However, the discriminative ability for HCC diagnosis was relatively low [AUC(95%CI): 0.623(0.570-0.675)]. Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline, was prognostic of higher rates of decompensation(P = 0.036), HCC development(P = 0.08), and liver-related deaths(P 0.001) during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination. In combination with APRI, its diagnostic performance can be further improved. Most importantly, the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.