Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

Long-term prognosis of cirrhotics with an upper gastrointestinal bleeding episode: Does infection play a role?

Background and Aim:  We evaluated the effect of infection on the short- and long-term outcome of cirrhotic patients with upper gastrointestinal bleeding (UGIB), in a series of patients not submitted to antibiotic prophylaxis.
Methods:  The cirrhotic patients hospitalized for UGIB were prospectively followed up until the last visit, death, or transplantation. A standard screening protocol was used for bacterial infection at admission.
Results:  In total, 205 patients were included in the study. Antibiotics were administered in 79 (38.5%) patients and an infection was documented in 64 (31.4%) patients. In total, 130 (63.4%) patients died after a mean (SD) follow up of 23.8 (30.9) months. Six-week mortality was higher in the infected patients ( P  < 0.0001). The mortality of patients who were alive 6 weeks after admission was not different between the infected and non-infected patients. Antibiotic use or bacterial infection, the Child–Pugh score, hepatocellular carcinoma, and creatinine were the independent predictors of 6-week mortality. Age and the Child–Pugh score were the only predictors of mortality of the patients who had survived for more than 6 weeks after acute bleeding. In total, 51 (24.9%) patients rebled, 37 (18.1%) within 5 days of admission. Rebleeding was more frequent (41.8% vs 14.3%, P  < 0.0001) in infected patients, mostly due to differences in early rebleeding (31.6% vs 9.5%, P  = 0.0001).
Conclusion:  Bacterial infection is associated with failure to control UGIB and early mortality in cirrhotic patients, but does not seem to affect the outcome of patients who overcome the bleeding episode.     

Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi-center study

Aim:  The differing efficacies of radiofrequency ablation and microwave coagulation for hepatocellular carcinoma (HCC) are unknown. Therefore, we performed a multi-center study to assess the factors contributing to survival and local recurrences of HCC among patients with solitary tumors who underwent endoscopic thermal ablation as their primary treatment.
Methods:  From six institutions, 391 patients with solitary HCC who were first treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. We investigated age, gender, location of tumor, longest diameter of tumor, method of anesthesia, type of endoscope, method of thermal ablation, Child–Pugh classification, the Japan Integrated Staging score and the Cancer of the Liver Italian Program score. Statistical analyses were performed using univariate analysis with log–rank test and multivariate analysis with the Cox proportional hazards model.
Results:  On univariate analysis, advanced Child–Pugh score, advanced Italian Program score and local recurrences were significant predictors of poor survival. Young age (≤70), large tumor (>30 mm) and the use of the thoracoscopic approach were significant predictors for the development of local recurrence. On multivariate analysis, local anesthesia and advanced Child–Pugh score were independent predictors of poor survival. Young age, large tumor, local anesthesia and the use of the thoracoscopic approach were independent predictors for the development of local recurrence. The method of thermal ablation did not influence survival or local recurrence.
Conclusions:  Differences in the effect on survival and local recurrence between microwave and radiofrequency were not observed in this retrospective, multi-center study of endoscopic thermal ablation for HCC.     

Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C

Background and Aim:  Ethnic differences in non-alcoholic steatohepatitis (NASH) are well-documented, but there has been no study on the prognosis of Japanese NASH patients with cirrhosis. Accordingly, we compared cirrhotic NASH with liver cirrhosis caused by chronic hepatitis C (LC-C) to clarify its clinical features and define the risk factors for death.
Methods:  A prospective evaluation of the outcomes of NASH patients with severe fibrosis was started in 1990. Data on age- and sex-matched patients with biopsy-proven LC-C were collected retrospectively and used as the control.
Results:  There were 68 patients with cirrhotic NASH and 69 with LC-C. The Child–Turcotte–Pugh (CTP) class was similar in these two groups. Although the outcome of the NASH group was better than that of the LC-C group, cirrhotic NASH followed a similar course to that of LC-C; that is, complications of cirrhosis developed, including hepatocellular carcinoma (HCC; the 5-year HCC rate was 11.3% for NASH and 30.5% for HCV) and death (the 5-year survival rates were 75.2% and 73.8%, respectively). HCC was the leading cause of death in both groups (NASH, 47%; HCV, 68%). The occurrence of HCC and the CTP class were significant risk factors for mortality in NASH patients according to a multivariate analysis (HCC: hazard ratio [HR] 7.96, 95% confidence interval [CI] 2.45–25.88, CTP class A: HR 0.17, 95% CI 0.06–0.50).
Conclusion:  In conclusion, the present study confirmed that cirrhotic NASH has a similar course to LC-C. The occurrence of HCC was the strongest predictor of mortality in the NASH groups. These findings may be helpful when deciding on therapeutic interventions for NASH and also for the daily management of these patients.     

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approach

Background and Aim:  Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis.
Methods:  Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis.
Results:  The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P  = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index ( P  = 0.53 and 0.34, respectively), Child–Pugh classification ( P  = 0.73 and 0.78, respectively) or glucagon levels ( P  = 0.59 and 0.62, respectively).
Conclusions:  The present data show no correlation between the presence or the severity of PHG and portal pressure, Child–Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.     

Evaluation of Quantitative Portal Venous, Hepatic Arterial, and Total Hepatic Tissue Blood Flow Using Xenon CT in Alcoholic Liver Cirrhosis: Comparison With Liver Cirrhosis C

Background/Aims: Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis C (C-LC).
Methods: Xenon computed tomography was performed on 12 patients with AL-LC and 17 patients with C-LC. The severity of LC was classified according to Child–Pugh classification. Correlations between hepatic TBF and Child–Pugh classification were examined. Correlations of hepatic TBF in Child–Pugh class A to C-LC and AL-LC were also examined.
Results: The mean portal venous TBF (PVTBF) was significantly lower in AL-LC than in C-LC ( p =0.0316). Similarly, the mean total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC ( p =0.0390). PVTBF displayed a significant negative correlation with Child–Pugh score ( r =−0.396, p =0.0368).
Conclusions: Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease.     

Clinical features and survival in Chinese patients with hepatitis B e antigen-negative hepatitis B virus-related cirrhosis

Aim:  To compare the clinical features of hepatitis B e antigen (HBeAg)-negative and HBeAg-positive cirrhosis, and to define the survival and prognostic indicators of Chinese HBeAg-negative hepatitis B virus (HBV)-related cirrhosis.
Methods:  Two hundred and seventeen patients with chronic hepatitis B cirrhosis were studied. Survival was calculated using the Kaplan–Meier method. Proportional hazards Cox regression procedure was used to identify independent predictors of survival. The relationship between HBV-DNA viral load and prognosis was also investigated.
Results:  The mean follow-up time was 35 months (3–47 months). HBeAg-negative liver cirrhosis patients comprised the greatest number of cirrhosis patients. Median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, median total leukocytes (WBC), hemoglobin (Hb), platelet (Plt) and HBV-DNA levels and the proportion of HBV-DNA > 10⁵ copies/mL were lower in HBeAg-negative patients. There were fewer complications in patients treated with lamivudine than in other patients. Survival rates were significantly reduced in patients with HBeAg-negative cirrhosis ( P  = 0.0024). The baseline Child–Pugh scores and more than one decompensation during follow up were independent variables correlated with survival of HBeAg-negative liver cirrhosis patients ( P  = 0.006 and P  = 0.001, respectively). The HBV-DNA viral load did not correlate with any complications or mortality rates of HBeAg-negative patients.
Conclusions:  The clinical features of HBeAg-negative and -positive liver cirrhosis differ. Survival was significantly reduced for Chinese patients with HBeAg-negative than -positive cirrhosis. Factors contributing to the prognosis were baseline Child–Pugh scores and the presence of more than one decompensation during follow up.     

Ascitic fluid infection in patients with hepatitis B virus-related liver cirrhosis: Culture-negative neutrocytic ascites versus spontaneous bacterial peritonitis

Background and Aim:  Ascitic fluid infection (AFI) consists of culture-negative neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The present study compared the clinical characteristics and prognosis of CNNA and SBP in hepatitis B virus (HBV)-related cirrhotic patients.
Methods:  We analyzed 130 consecutive patients hospitalized due to the first episode of AFI between January 1998 and December 2007.
Results:  The mean age of the patients was 52.3 years (88 men, 42 women). Ninety-three patients (71.5%) had CNNA and 37 patients (28.5%) had SBP; 117 patients (90.0%) died after a median survival period of 6.4 months. Patients with CNNA and SBP survived for a median period of 6.9 months and 5.4 months, respectively ( P  = 0.417). Patients with SBP showed higher in-hospital mortality than those with CNNA (16.2 vs 4.3%; P  = 0.031). Binary logistic regression analysis showed that culture positivity of ascitic fluid (CNNA vs SBP) was the only independent predictor of in-hospital mortality ( P  = 0.042). In a Cox regression model for the 120 patients (92.3%) who survived the first episode of AFI, only the Child–Pugh score remained significant for survival ( P  = 0.007), whereas no association was observed for culture positivity of ascitic fluid (CNNA vs SBP) during the first episode of AFI ( P  = 0.752).
Conclusions:  Although in-hospital mortality was higher in patients with SBP than CNNA, the clinical course of the two groups was similar after the first episode of AFI. Thus, liver transplantation should be considered, irrespective of culture positivity of ascitic fluid.     

Analysis of Hepatic Vein Waveform by Doppler Ultrasonography in 100 Patients with Portal Hypertension

Objectives : We classified the Doppler waveform seen in patients with portal hypertension and examined the associations of the waveform type with the diagnosis of Budd-Chiari syndrome and severity of the liver cirrho-sis. Methods : The Doppler pattern of right and left hepatic veins in 100 consecutive Japanese patients with portal hypertension and esophagogastric varices was classified into six types: 1, triphasic waveform; IF, bi-phasic waveform without reversed flow; III, decreased amplitude of phasic oscillations; IV, flat waveform with fluttering; V, completely flat waveform with fluttering; VI, no waveform. All patients underwent computed tomography and magnetic resonance imaging. Patients in whom hepatic vein waveform showed type IV, type V, or type VI, positively underwent hepatic venography and inferior vena cavography. Resuits: Type I was seen in 31 of 100 patients, type II in 35, type III in 17, type IV in eight, type V in four, and type VI in five. Types I-IV waveform indicated no lesion in hepatic veins and inferior vena cava, type V indicated stenosis of hepatic veins or occlusion of inferior vena cava, and type VI, occlusion of hepatic veins. For one patient with type V hepatic veins, halloon angioplasty was done, and the waveform changed from type V to type II. Examining the relationship between hepatic vein waveform and the Child-Pugh score, liver function of type IV cases was worse than tbat of type I cases in 66 cirrhotie patients witbout bepatocellular carcinoma(p < 0.05). Tbere was no clear relutionship between bepatic vein waveform and portal venous perfusion, as based on Nordlinger's grade. Conclusions: Our classiflcation of hepatic vein waveform in Doppler ultrasonography is useful in di-agnosing Budd-Cbiari syndrome, in judging the effi-ciency of treatment for bepatic vein lesions, and in assessing severe liver function in cirrbotic patients.     

Urinary bile acid sulfate levels in patients with hepatitis C virus-related chronic liver diseases

Aim:  Urinary bile acids are mainly conjugated with sulfuric acid, and urinary sulfated bile acid (USBA) levels in hepatobiliary diseases have been reported. However, the relationship between USBA and fasting serum total bile acid (TBA) has not been studied in hepatobiliary diseases. In the present study, we measured USBA levels in patients with hepatitis C virus-related chronic liver diseases, and the relationship between TBA and various laboratory tests was studied.
Methods:  USBA was measured using an automatic assay kit in 66 patients with chronic hepatitis and 28 patients with liver cirrhosis, and its relationship between TBA and various laboratory tests was studied.
Results:  The median USBA level was 10.7 µmol/g creatinine in patients with chronic hepatitis and 41.1 µmol/g creatinine in liver cirrhosis ( P  = 0.000). More patients with chronic hepatitis had elevated USBA levels (61%) compared to TBA level (39%) ( P  = 0.002). USBA level was well correlated with TBA (r_s = 0.680), and negatively correlated with albumin (r_s = −0.488), prothrombin time (r_s = −0.385) and platelet counts (r_s = −0.394). In patients with liver cirrhosis, USBA was significantly elevated in Child–Pugh class B compared to Child–Pugh class A ( P  = 0.036).
Conclusion:  Although the metabolic pathways of USBA and TBA are different, these levels correlated very well, and USBA is considered to be a useful indicator of hepatic function like TBA in patients with chronic hepatitis C.     

Fine-needle aspiration cytology to distinguish dysplasia from hepatocellular carcinoma with different grades

Background:  Distinguishing dysplasia from hepatocellular carcinoma (HCC) by fine-needle aspiration (FNA) cytology is difficult. The aim of this study was to diagnose HCC and the distinction of liver cell dysplasia from HCC with different grades by interpreting and scoring the cyto-morphological features.
Methods:  Eighty-three cirrhotic patients undertook a sonography-guided FNA and subsequent needle biopsy for the tumor. HCC was confirmed in 68 cases and cirrhosis with dysplasia in 15 cases by pathology and follow-up for longer than 2 years. Eighteen cytological features were scored as degree of one, two or three according to their presence or prominence.
Results:  Two cases of well-differentiated HCC were diagnosed as negative for HCC initially. The sensitivity, specificity, false positive, false negative and accuracy were 97%, 100%, 0%, 3% and 97.6% for FNA cytology in the diagnosis of HCC, respectively. The score of dysplasia was 20.8 ± 1.3 (mean ± SD) and lower than 26.2 ± 3.4 in Edmondson's grade I HCC ( P  < 0.01), 28.9 ± 2.9 in grade II HCC ( P  < 0.01), and 34.9 ± 4.3 in grade III/IV HCC ( P  < 0.01). The score was also significantly lower in grade II HCC than in grade III/IV HCC ( P  < 0.01).
Conclusions:  FNA yielded a high accuracy in the distinction of dysplasia from HCC with different grades. There is a good correlation in cyto-morphological scores of liver cell dysplasia and HCC with different grades. Dysplasia displayed the lowest score and the score increased in order from dysplasia to grade III/IV HCC.     

Prognostic Significance of Hepatic Vein Waveform by Doppler Ultrasonography in Cirrhotic Patients with Portal Hypertension

Objective: We prospectively evaluated the prognostic value of the flat hepatic vein waveform, measured by Doppler ultrasound, in cirrhotic patients with portal hypertension.
Methods: The Doppler pattern of right and left hepatic veins in a series of 120 consecutive cirrhotic patients with portal hypertension but without hepatocellular carcinoma was examined, together with clinical and biochemical parameters.
Results: Flat waveform of the right hepatic vein was recognized in nine patients and that of the left hepatic vein was seen in 13. After a mean follow-up of 13.6 ± 9.7 months, 17 patients died, all from liver failure. In the univariate analysis, variables significantly associated with the duration of survival were age, etiology of the liver cirrhosis, upper gastrointestinal bleeding after start of the study, Child-Pugh score, ascites, encephalopathy, prothrombin index, bilirubin, albumin, and flat Doppler waveform in the right and left hepatic veins. Multivariate analysis showed that flat Doppler waveform in the right hepatic vein, bilirubin, and prothrombin index were independently related to survival.
Conclusions: The prognostic accuracy in cases of cirrhosis with portal hypertension is significantly improved with acquistion of information obtained from hepatic vein waveform by Doppler ultrasound.     

Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study.

BACKGROUND AND AIMS: Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis. MATERIAL AND METHODS: In 76 patients with cirrhosis (69 men and seven women), both DI of Doppler HV waveform and HVPG were measured, and the relationship between them was analysed. DI was calculated by the minimum velocity/maximum velocity of the HV waveform. An HVPG>12 mmHg was defined as severe portal hypertension. In a subgroup of 19 patients receiving propranolol, changes in both DI and HVPG were evaluated after propranolol administration for 3 months. One author (S. K. B.) performed all DI of Doppler HV waveform studies. RESULTS: Abnormal HV waveforms were seen in 66 of 76 patients (86.8%). DI significantly correlated with the grade of HVPG, i.e. with higher HVPG increased DI was observed (P<0.01). By logistic regression analysis, DI>0.6 was significantly more likely to be severe portal hypertension (odds ratio: 14.19, 95% confidence interval: 4.07-49.55). Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9% and a specificity of 81.8% for the presence of severe portal hypertension. In 19 patients of the propranolol subgroup, change of DI following propranolol treatment also significantly correlated with that of HVPG (P<0.01). CONCLUSIONS: Damping index of the HV waveform by Doppler ultrasonography might be a non-invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis.     

Correlation of routinely used coagulation parameters and presence of portal vein thrombosis in patients with liver cirrhosis

Aim:  Portal vein thrombosis (PVT) is a serious complication in patients with liver cirrhosis. In patients with advanced stages of liver cirrhosis plasmatic coagulation and platelet count are often reduced. However, patients with normal coagulation status might carry a high risk for developing PVT. A correlation between coagulation status used in clinical routine and the incidence of PVT in patients with liver cirrhosis has been evaluated in the present retrospective analysis.
Methods:  88 patients with liver cirrhosis were identified by screening a database. Of these patients, 23 suffered from PVT. Patients were classified according to the Child–Pugh classification. Patients were subdivided into early stages (Child A) and advanced stages (Child B/C) of liver cirrhosis.
Results:  In patients with Child–Pugh A cirrhosis, there was no difference in activated partial thromboplastin time (apTT), international normalized ratio (INR), and platelet count between the PVT ( n  = 7) and the control group ( n  = 35). In contrast, the median apTT and INR were significantly lower in patients with Child B/C cirrhosis and PVT ( n  = 16) in comparison with patients without PVT (37 s vs 43 s [ P  = 0.017] and 1.25 vs 1.40 [ P  = 0.022]), respectively. Platelet count did not differ significantly in patients with advanced liver cirrhosis and PVT from those without PVT.
Conclusion:  Patients with advanced liver cirrhosis and PVT displayed lower apTT and INR compared with those without PVT. Therefore, patients with advanced liver cirrhosis and almost normal coagulation parameters might be at particular risk of developing PVT. The results suggest that regular monitoring using Doppler-ultrasound should be carried out in these patients, especially when liver transplantation is intended.     

Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction

Background and Aims:  Increased levels of nitric oxide (NO) are hypothesized to contribute to renal dysfunction in patients with decompensated cirrhosis. In this study, we examined whether splanchnic and/or peripheral NO levels and L-arginine (L-Arg) correlate with progressive renal dysfunction in cirrhotics.
Methods:  Serum NO metabolites (NOx) and L-Arg were measured in: controls ( n  = 10); organ donors ( n  = 12); compensated cirrhotics ( n  = 17), cirrhotics with ascites ( n  = 25), refractory ascites ( n  = 11) or hepatorenal syndrome type II (HRS) ( n  = 11) and chronic renal failure patients ( n  = 18).
Results:  Plasma NOx and L-Arg levels rose progressively with worsening renal function in decompensated cirrhotics. Both NOx and L-Arg levels were highest in patients with HRS ( P  < 0.001 and P  < 0.025, respectively). While there were no differences in NOx levels related to the site of sampling, L-Arg levels were lowest in hepatic venous blood. There were significant relationships of NOx and L-Arg with Model for End-Stage Liver Disease score and Child–Pugh scores ( P  < 0.04 and P  < 0.01, respectively). Multivariate analysis showed a significant relationship between NOx, L-Arg and HRS.
Conclusion:  Worsening renal function in decompensated cirrhosis is accompanied by progressive elevation in plasma NOx and L-Arg. These findings support the hypothesis that NO-mediated vasodilation is probably linked with the mechanism of progressive renal failure in decompensated cirrhotics.     

Validation of model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor in patients with cirrhosis

Aim:  To evaluate the prognostic ability of model for end-stage liver disease (MELD) to serum sodium (SNa) ratio (MESO) index and to compare the predictive accuracy of the MESO index with the MELD score and the modified Child–Turcotte–Pugh (CTP) score for short-term survival in cirrhotic patients.
Methods:  A total of 256 patients with cirrhosis were retrospectively evaluated. The predictive accuracy of the MESO index, MELD score and modified CTP score were compared by the area under the receiver–operator characteristic curve (AUC).
Results:  Using 1-month and 3-month mortality as the end-point, overall, MESO and MELD were significantly better than the CTP score in predicting the risk of mortality at 1 month (AUC, 0.866,0.819 vs 0.722, P  < 0.01) and 3 months (AUC, 0.875,0.820 vs 0.721, P  < 0.01). In the low MELD group, the AUC of MESO index (0.758, 0.759) and CTP score (0.754, 0.732) were higher than that of the MELD score (0.608, 0.611) at 1 month and 3 months, respectively ( P  < 0.01). However, in the high MELD group, the AUC of MESO index (0.762, 0.779) and MELD (0.737, 0.773) were higher than that of the CTP score (0.710, 0.752) at 1 month and 3 months, respectively, although there were no significant differences ( P  > 0.05). With appropriate cut-offs for the MESO index, the mortality rate of patients in high MESO was higher (57.1% at 1 month and 69.2% at 3 months) than that of the low MESO (5.5% at 1 month and 7.9% at 3 months) ( P  < 0.01).
Conclusions:  The MESO index, which adds SNa to MELD, is a useful prognostic marker and is found to be superior to the MELD score and modified CTP score for short-term prognostication of patients with cirrhosis.     

Platelet aggregation is significantly associated with cardiovascular mortality in elderly patients

Background:   The relationship between cardiovascular mortality and platelet function in elderly patients remains unclear.
Methods:   The outcomes for 347 consecutive patients aged 60 or older (mean age 77.5 years; 161 men and 186 women) who were treated without antiplatelet drugs on registration, were retrospectively studied after platelet aggregatability tests. The grading curve (GC) type, as an index of platelet aggregatability, was determined with an aggregometer and adenosine-5'-diphosphate as an agonist. Patients were classified into three groups according to GC type: Group I with suppressed aggregation ( n  = 40); Group II, normal aggregation ( n  = 208); and Group III, increased aggregation ( n  = 99). The mean follow-up was 3.9 years.
Results:   There were three deaths in Group I, 33 in Group II, and 30 in Group III. The mean annual mortality rate was 2.1% in Group I, 4.0% in Group II and 7.5% in Group III. Although the most common cause of death was pneumonia in all three groups, the annual mortality rates due to vascular events were 0.7% in Group I, 0.6% in Group II and 4.2% in Group III. Cox proportional hazards models for vascular death yielded a hazard ratio of 1.5 in the increased GC type.
Conclusion:   These findings indicated that elderly patients with accelerated aggregation had higher mortality rates due to vascular events. Therefore, accelerated aggregation in the elderly suggested not only the progress of arteriosclerosis, but indications of antiplatelet therapy to prevent vascular events.     

Treatment of patients with gastric variceal hemorrhage: Endoscopic N-butyl-2-cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration

Background and Aim:  Our study aimed to evaluate the therapeutic results of endoscopic N-butyl-2-cyanoacrylate injection (EBC) and balloon-occluded retrograde transvenous obliteration (BRTO) in patients with gastric variceal hemorrhage (GVH) and/or high-risk gastric varices (GV).
Methods:  Twenty-seven patients with GVH and/or high-risk GV (≥ 5 mm in diameter, those with red spots, and a Child–Pugh grading of B or C liver cirrhosis) who were treated with either EBC or BRTO from April 2005 to December 2007 were included in our study.
Results:  EBC or BRTO was initially used for the treatment of GVH in 14 and 13 patients, respectively. Technical success was achieved in all 14 patients (100%) initially treated with EBC, and 10 of 13 patients (76.9%) initially treated with BRTO. Significant rebleeding occurred in 10 patients (71.4%) of the EBC group, and two patients (15.4%) of BRTO group ( P  < 0.01). Five of six patients (83.3%) treated with rescue BRTO due to rebleeding after initial EBC achieved technical success, and all six patients who were treated with rescue BRTO had no rebleeding during the median follow up of 17 (range: 2–37) months. The cumulative survival rate of the EBC with the BRTO rescue group/BRTO group was significantly higher than the EBC group.
Conclusion:  The therapeutic efficacies of EBC and BRTO for the treatment of active GVH and/or high-risk GV appeared to be similar. However, EBC might be associated with a higher rebleeding rate than BRTO. BRTO could be an effective rescue treatment for patients with GVH after initial treatment of EBC.     

Intestinal metaplasia in portal hypertensive gastropathy: a frequent pathology

OBJECTIVE: To compare the frequency of intestinal metaplasia (IM) in patients with portal hypertensive gastropathy (PHG) to the control group with functional dyspepsia. METHODS: Two-hundred and eighty-nine cases were prospectively evaluated in three groups (controls:group I--123 patients; cirrhotics: group II--135 patients; noncirrhotic portal hypertensives: group III--31 patients). Mucosal biopsies (three antrum, one angulus, two corpus) were taken and examined for atrophy, IM, dysplasia, Helicobacter pylori (Hp) and histologic PHG. RESULTS: Frequencies of IM in groups I, II and III were 17.1% (type I, 3.3%; type II, 10.6%; type III, 3.3%), 34.3% (type I, 9.6%; type II, 17%; type III, 6.7%) and 33.3% (type I, 9.7%; type II, 12.9%; type III, 9.7%), respectively. In patients with PHG, frequency of IM was significantly higher than in control group (P<0.05) and correlated with the severity of PHG (P<0.05). The frequency of type III IM was not statistically different among the three groups. Frequency of atrophy in cirrhotic patients was higher than in control group (17.9% in group I, 32.6% in group II, 25.8% in group III; P<0.05). In the control group, Hp prevalence was significantly higher than in patients with PHG (P<0.05) and there was a positive correlation between Hp and atrophy (P<0.05). In multivariate analysis, PHG and age were found as independent predictors for IM; PHG, age and Hp for atrophy. CONCLUSION: Frequencies of atrophy and IM are higher in patients with PHG. PHG is a reliable marker for IM and atrophy in gastric mucosa.