Evaluation of quantitative portal venous, hepatic arterial, and total hepatic tissue blood flow using xenon CT in alcoholic liver cirrhosis-comparison with liver cirrhosis related to hepatitis C virus and nonalcoholic steatohepatitis

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 related to nonalcoholic steatohepatitis (NASH), (NASH-LC), and hepatitis C virus (HCV), (C-LC). Methods: Xe-CT was performed on 22 patients with AL-LC, 7 patients with NASH-LC, and 24 patients with C-LC. Severity of LC was classified according to Child-Pugh classification. Correlations between hepatic TBF, Child-Pugh classification, and indocyanin green retention (ICG) rate after 15 minutes (ICG15R) were examined. Correlations of hepatic TBF in Child-Pugh class A to AL-LC, NASH-LC, and C-LC were also examined. Results: Portal venous TBF (PVTBF) displayed a significant negative correlation with Child-Pugh score and ICG15R (r = −0.432, p < 0.01, r = −0.442, p < 0.01, respectively). Moreover, ICG15R displayed a significant positive correlation with Child-Pugh score (r = 0.661, p < 0.001). Meanwhile, mean PVTBF and total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC (p < 0.05). Mean PVTBF was significantly lower in Child-Pugh class A to AL-LC and NASH-LC than in that to C-LC (p < 0.05). Similarly, mean THTBF was significantly lower in Child-Pugh class A to NASH-LC than in that to C-LC (p < 0.05). 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.     

Xenon computed tomography shows hemodynamic change during the progression of chronic hepatitis C

Aim: Xenon computed tomography (Xe-CT) is a non-invasive method of quantifying and visualizing tissue blood flow (TBF). Xe-CT allows separate measurement of hepatic arterial and portal venous flow. The aim of this study was to investigate correlations between the progression of fibrosis and hemodynamic changes in chronic hepatitis C (CHC) patients using Xe-CT. Methods: Separate measurements of portal venous TBF (PVTBF) and hepatic arterial TBF (HATBF) were performed using Xe-CT, and total hepatic TBF (THTBF) was calculated as the sum of PVTBF and HATBF. A total of 50 patients with CHC underwent Xe-CT. Liver biopsy was performed on 42 of the 50 patients, and hepatic fibrosis was classified as mild (F1), moderate (F2), severe (F3) or Child-Pugh class A cirrhosis (F4a). In addition, eight patients with Child-Pugh class B cirrhosis (F4b) were evaluated. Results: Significant negative correlations were identified between PVTBF and progression of stage (r(s) = -0.622, P < 0.0001) and between THTBF and progression of stage (r(s) = -0.458, P = 0.0041). Conclusion: Separate measurement of PVTBF and HATBF using non-invasive Xe-CT provided quantitative and visual information regarding hemodynamics of the entire liver in CHC patients. PVTBF decreases with the progression of fibrosis, even in CHC patients.     

Xenon computed tomography can evaluate the improvement of hepatic hemodynamics before and after endoscopic injection sclerotherapy

Background

Xenon computed tomography (Xe-CT) provides quantitative information on tissue blood flow (TBF). In the present study, Xe-CT was performed in patients with esophagogastric varices (EGV) before and after endoscopic injection sclerotherapy (EIS) to evaluate hepatic blood flow (HBF), hepatic arterial TBF (HATBF) and portal venous TBF (PVTBF).

Methods

Subjects comprised of 88 patients with EGV (49 men, 39 women, average age 65.8 ± 11.5 years, median age 68 years, 30–86 years) and liver cirrhosis related to either hepatitis C virus (C) (n = 33), hepatitis B virus (B) (n = 3), alcohol (AL) (n = 22), AL + C (n = 7), AL + B (n = 1), B + C + AL (n = 1), nonalcoholic steatohepatitis (NASH) (n = 4), autoimmune hepatitis (AIH) (n = 5), primary biliary cirrhosis (PBC) (n = 2), or cryptogenic (n = 10) were enrolled. All patients, who were enrolled in this study, were performed EIS for prophylaxis. Xe-CT and measurement of the retention rate of indocyanine green 15 min after administration (ICG R15) were performed before and after EIS. Total hepatic TBF (THTBF) and PVTBF/HATBF ratio (P/A) were also calculated.

Results

PVTBF, HATBF, THTBF, P/A and ICG R15 before EIS were 28.3 ± 8.91, 22.5 ± 14.4 and 50.8 ± 17.6 ml/100 ml/min, 1.62 ± 0.71 and 28.8 ± 12.7 %, respectively and those after EIS were 31.9 ± 10.0, 19.3 ± 11.6, and 51.2 ± 17.0 ml/100 ml/min, 1.92 ± 0.84 and 23.6 ± 11.3 %, respectively. PVTBF and P/A after EIS were significantly higher than those before EIS (p = 0.00444, p = 0.0179, respectively), and HATBF and ICG R15 after EIS were significantly lower than those before EIS (p = 0.00129, p < 0.001, respectively).

Conclusions

Xenon computed tomography showed that PVTBF increased after EIS for EGV and HATBF decreased in response to an increase in PVTBF.     

Regulation of Hepatic Thrombopoietin Production by Portal Hemodynamics in Liver Cirrhosis

Objective: This study was designed to clarify how thrombopoietin (TPO) functions in and, to some extent, causes thrombocytopenia complicating liver cirrhosis and portal hypertension.
Methods: Our study population consisted of 19 cirrhotic and six noncirrhotic patients who underwent percutaneous transhepatic portography (PTP) and hepatic venography.
Results: The platelet counts of the cirrhotic patients were significantly lower than those of the noncirrhotic patients (  8.7 ± 4.1 vs 17.4 ± 7 × 10⁴/μl  ;   p < 0.01  ). The flow direction in the splenic vein was confirmed by PTP. Ten hepatofugal and nine hepatopetal flow directions in the splenic vein were noted among the cirrhotics. The hepatofugal group showed lower portal venous pressure (  20 ± 10 vs 32 ± 4 cm H₂O  ;   p < 0.01  ) than the hepatopetal group and had a higher incidence of hepatic encephalopathy (six of 10 vs zero of nine;   p < 0.01  ). The hepatic vein-portal difference in TPO did not differ substantially between the cirrhotics and noncirrhotics (  0.12 ± 0.04 vs 0.24 ± 0.07  fmol/ml). Comparisons of this value among the three groups showed the TPO difference to be lowest in the hepatofugal group (hepatofugal:  0.04 ± 0.03  , hepatopetal:  0.21 ± 0.07  , noncirrhotic:  0.24 ± 0.07  ;   p < 0.05  ).
Conclusions: Our findings suggest that TPO production in the cirrhotic liver is regulated by the portal blood supply to the liver. Thus, portal hemodynamics may play a critical role in the development of thrombocytopenia.     

Pathophysiological analysis of nonalcoholic fatty liver disease by evaluation of fatty liver changes and blood flow using xenon computed tomography: can early-stage nonalcoholic steatohepatitis be distinguished from simple steatosis?

Introduction

Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS.

Materials and methods

We used Fick’s principle and the Kety–Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt’s classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups.

Results

LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups.

Conclusions

In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means.     

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.     

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.     

Abnormality of the hepatic vein waveforms in cirrhotic patients with portal hypertension and its prognostic implications

Background and Aim:  We investigated the prognostic significance of changes in the Doppler hepatic vein (HV) waveforms in cirrhotic patients with portal hypertension and the mechanisms of these changes.
Methods:  A total of 103 consecutive patients were included in this study and their HV waveforms were classified into four types: type I, triphasic waveform; type II, biphasic waveform; type III, biphasic waveform with reduced phasic oscillations; and type IV, a flat waveform.
Results:  Type I was observed in 34, type II in 40, type III in 23, and type IV in six patients. The 5-year survival rates were 90%, 89%, 41%, and 0% in type I, II, III, and IV, respectively. Five variables including the Child–Pugh score, albumin, bilirubin, ascites, and HV waveform significantly correlated with the survival in a univariate analysis. A multivariate analysis only identified the HV waveform (type III and IV) to be an independent prognostic value. Even in Child–Pugh class B patients, the 5-year survival rate for type III or IV was as poor as 26% in comparison to 92% for type I or II. In contrast, in Child–Pugh class C patients, the 5-year survival rate for type I or II was as good as 63% in comparison to 25% for type III or IV. Furthermore, the changes in HV waveforms correlated with the extent of hepatic fibrosis, the increase in portal perfusion per liver volume, or the decrease in portal vascular resistance.
Conclusions:  Analyzing the HV waveforms was thus found to be a simple method for accurately assessing the prognosis in cirrhotic patients with portal hypertension.     

Clinical Characteristics of Portal Hemodynamics in Alcoholic Liver Cirrhosis

Background: Low incidence of reversal blood flow at the portal vein has been reported by measurement in larger and extrahepatic blood vessels but not in intrahepatic blood vessels in patients with liver cirrhosis. Moreover, there is little information regarding the incidence of reversal blood on the basis of the cause of liver cirrhosis. The aim of this study was to measure the reversal blood flow in the portal vein including intrahepatic branches in patients with alcoholic and viral cirrhosis.
Methods: The blood flow in the portal vein and existence of portosystemic shunt were studied in 52 and 27 patients with alcoholic and viral cirrhosis, respectively, by Doppler ultrasonography. The parameters of liver function test and the prevalence of ascites and esophageal varices were compared between patients with and without reversal blood flow.
Results: Reversal blood flow at the portal vein was found only in patients with only alcoholic cirrhosis (17 of 52 patients) but not in any patients with viral cirrhosis (0 of 27 patients; p < 0.05). The incidence of portosystemic ascites and red color of esophageal varices was also higher in patients with alcoholic cirrhosis with reversal blood flow in the portal vein compared with patients without reversal blood flow ( p < 0.05).
Conclusions: Reversal blood flow in the portal vein is a characteristic feature of alcoholic cirrhosis. The presence of reversal blood flow indicates severe liver diseases, and this feature may have prognostic importance for patients with alcoholic cirrhosis.     

Nicardipine Infusion Improved Hepatic Function But Failed to Reduce Hepatic Venous Pressure Gradient in Patients with Cirrhosis

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.     

Intrahepatic Heterogeneity of Hepatic Venous Pressure Gradient in Human Cirrhosis

Background: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension. Methods: We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls). Results: In the controls, the two measurements differed by 0.0 ± 1.8 mmHg (mean ± s , n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s ). HVPG ranged from-0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within ± 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature. Discussion: Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.     

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.     

Hepatic arterial pulsatility index in cirrhosis: correlation with portal pressure.

BACKGROUND/AIMS: Determination of the pulsatility index by means of duplex sonography provides the opportunity to evaluate the vascular resistance of the hepatic artery noninvasively. The aim of this study was to investigate the relationship between the hepatic arterial pulsatility index and the hepatic venous pressure gradient in cirrhosis. METHODS: In 50 patients with cirrhosis, hepatic venous pressure gradient was determined in the fasting state. Immediately thereafter, hepatic arterial pulsatility index and portal blood flow velocity were measured by duplex sonography with no knowledge of hepatic venous pressure values. In addition, the duplex parameters were determined in 20 controls. RESULTS: Hepatic arterial pulsatility index was significantly higher in patients with cirrhosis than in controls (0.92+/-0.1 vs. 1.14+/-0.18; p<0.001) and directly correlated with the hepatic venous pressure gradient (r = 0.7; p<0.001). Furthermore, weak correlations were found between hepatic arterial pulsatility index and Child-Pugh score (r = 0.49; p<0.01) and between portal blood flow velocity and hepatic venous pressure gradient (r = -0.48; p<0.01). CONCLUSION: In cirrhosis the hepatic arterial vascular resistance seems to increase parallel to the rise of the portal pressure. Therefore, duplex sonographic determination of the hepatic arterial pulsatility index may contribute to the noninvasive evaluation of portal hypertension.     

Assessment of hepatic steatosis and hepatic tissue blood flow by xenon computed tomography in nonalcoholic steatohepatitis

Aim:  The diagnosis of non-alcoholic steatohepatitis (NASH) can be difficult using blood tests and imaging studies. Histological diagnosis by liver biopsy remains the gold standard of NASH diagnosis. There is an urgent need to develop and validate simple, reproducible, noninvasive tests to accurately assess NASH stage and grade. We assess the usefulness of xenon computed tomography (Xe-CT), as a non-invasive method of quantitatively and visually determining hepatic tissue blood flows (TBFs), and xenon solubility (λ value) simultaneously with TBF, in the evaluation of NASH pathophysiology.
Methods:  Histological severity of fatty changes and severity of fibrosis based on Brunt's classification were determined in 38 NASH patients. We evaluated correlations between the grade of fatty changes and λ value, and correlations between the stage of fibrosis and TBFs.
Results:  The λ value showed significant positive correlations with both grade of steatosis ( r  = 0.813, P  < 0.001) and each 10% range of histological fatty infiltration ( r  = 0.926, P  < 0.001). A significant negative correlation was seen between λ value and the liver : spleen ratio ( r  = −0.835, P  < 0.001). Portal venous tissue blood flow and total hepatic tissue blood flow showed significant negative correlations with the progression of fibrosis ( r  = −0.465, P  < 0.01; r  = −0.433, P  < 0.01, respectively). Total hepatic tissue blood flow tended to decrease with progressing grade of steatosis.
Conclusion:  Xe-CT offers a convenient and objective method for evaluating fatty infiltration and changes in blood flow in the entire liver, and appears useful for detailed evaluation of patients with NASH.     

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

AIM:To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis(AL-LC).METHODS:The subjects included 35 patients with ALLC(34 men,1 woman;mean age,58.9±10.7 years;median age,61 years;range:37-76 years).All patientswere enrolled in this study after obtaining written informed consent.Liver function was measured with tests measuring albumin(Alb),prothrombin time(PT),brain natriuretic peptide(BNP),branched amino acid and tyrosine ratio(BTR),branched chain amino acid(BCAA),tyrosine,ammonia(NH3),cholinesterase(Ch E),immunoreactive insulin(IRI),total bile acid(TBA),and the retention rate of indocyanine green 15 min after administration(ICG R15).Hepatic blood flow,hepatic arterial tissue blood flow(HATBF),portal venous tissue blood flow(PVTBF),and total hepatic tissue blood flow(THTBF)were simultaneously calculated using xenon computed tomography.RESULTS:PVTBF,HATBF and THTBF were 30.2±10.4,20.0±10.7,and 50.3±14.9 m L/100 m L/min,respectively.Alb,PT,BNP,BTR,BCAA,tyrosine,NH3,Ch E,IRI,TBA,and ICG R15 were 3.50±0.50 g/d L,72.0%±11.5%,63.2±56.7 pg/m L,4.06±1.24,437.5±89.4μmol/L,117.7±32.8μmol/L,59.4±22.7μg/d L,161.0±70.8 IU/L,12.8±5.0μg/d L,68.0±51.8μmol/L,and 28.6%±13.5%,respectively.PVTBF showed a significant negative correlation with ICG R15(r=-0.468,P<0.01).No significant correlation was seen between ICG 15R,HATBF and THTBF.There was a significant correlation between PVTBF and Alb(r=0.2499,P<0.05),and NH3 tended to have an inverse correlation with PVTBF(r=-0.2428,P=0.0894).There were also many significant correlations between ICG R15 and liver function parameters,including Alb,NH3,PT,BNP,TBA,BCAA,and tyrosine(r=-0.2156,P<0.05;r=0.4318,P<0.01;r=0.4140,P<0.01;r=0.3610,P<0.05;r=0.5085,P<0.001;r=0.4496,P<0.01;and r=0.4740,P<0.05,respectively).CONCLUSION:Our investigation showed that there is a close correlation between liver function and hepatic blood flow.     

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.     

Reduction of Portal Pressure by Chronic Administration of Isosorbide Dinitrate in Patients with Cirrhosis: Effects on Systemic and Splanchnic Hemodynamics and Liver Function

We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with 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.     

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.     

Baseline and salt-stimulated paraoxonase and arylesterase activities in patients with chronic liver disease: relation to disease severity

Background: It has been recently reported that serum paraoxonase (PON1) and arylesterase (ARE) activities may be significantly reduced in patients with chronic liver disease. The aim of the study was to investigate the relations between serum PON1 and ARE activities and the degree of liver damage in patients with chronic liver injury.
Methods: We studied a total of 75 patients with chronic liver disease (50 patients with cirrhosis and 25 patients with chronic hepatitis) and 25 healthy comparison subjects. Baseline and salt-stimulated PON1 and ARE activities were determined in all study participants.
Results: Baseline and stimulated PON1 and ARE activities were significantly lower in patients with chronic liver disease than in controls. Cirrhotic patients in Child–Pugh classes B and C subgroups had significantly reduced PON1 and ARE activities compared with Child–Pugh class A patients (both P -values <0.01). Receiver operating characteristic curve analysis showed that serum ARE activity was the most efficient test for identifying the presence and severity of chronic liver injury.
Conclusion: Baseline and stimulated PON1 and ARE activities are reduced in patients with chronic liver disease. Serum ARE activity could be a suitable biomarker for the evaluation of the presence and severity of chronic liver damage.