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.     

The long-term course of chronic hepatitis B.

The aim of this study was to assess the long-term outcome in hepatitis B virus (HBV)-infected patients according to HBV, hepatitis C virus (HCV), and hepatitis D virus (HDV) replication, focusing on survival, liver failure, and hepatocellular carcinoma (HCC). A cohort of 302 hepatitis B surface antigen (HBsAg)-positive subjects (mean age, 34 +/- 15.3 years; male/female 214/88; 39 subjects under 14 years) with biopsy-proven chronic hepatitis (86 with cirrhosis) was prospectively assessed, with a median follow-up of 94 +/- 37.6 months. One hundred nine patients received interferon alfa (IFN). At baseline, 86 subjects (28.5%) were hepatitis B e antigen (HBeAg)-positive (wild-type HBV), 80 (26.5%) were HBeAg-negative, HBV-DNA-positive, 76 (25.2%) had HDV infection, 43 (14.2%) had dual HBV/HCV infection, and 17 (5.6%) were negative for HBV-DNA, anti-HCV, and anti-HDV. During follow-up, decompensation of disease occurred in 46 subjects: 8 developed HCC, 36 developed ascites, and 2 developed jaundice. Five patients underwent transplantation. Thirty-five subjects died: 33 of hepatic and 2 of nonhepatic causes. Overall mortality was 5.2-fold that of the general population (95% CI: 3.6-7.3; 35 deaths observed, 6.7 expected; P <.0001). By Cox regression analysis, survival was independently predicted by young age, absence of cirrhosis at baseline, and sustained normalization of aminotransferases during follow-up. Survival without decompensation was independently predicted by the same factors and by IFN treatment. Chronic hepatitis B infection increases mortality in comparison with the general population in our area regardless of specific virological profiles at presentation. Presence of cirrhosis and persistent necroinflammation markedly increase the risk of death.     

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.     

Natural history of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection can cause chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Chronic hepatitis B is characterized by an early replicative phase with hepatitis B e antigen (HBeAg) positivity, high serum HBV-DNA levels and disease activity (HBeAgpositive chronic hepatitis), and a late inactive phase with anti-HBe seroconversion, low or undetectable serum HBV-DNA, and liver disease remission (inactive carrier state). Another form is characterized by active disease due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). Both types of chronic hepatitis B can lead to cirrhosis and its complications. The incidence of cirrhosis is two to five per 100 person-years, but may be as high as eight to 10 in HBeAg-negative cases. The incidence of HCC varies geographically and increases with the duration and severity of liver disease (0.1 to 8 per 100 person-years). The prognosis is reasonably good in compensated cirrhosis, but very poor following decompensation. Viral and environmental factors influence the natural history of chronic hepatitis B and explain the heterogeneity of its clinical outcomes.     

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.     

The long-term outcome of interferon-alpha treated and untreated patients with HBeAg-negative chronic hepatitis B

BACKGROUND/AIMS: This study aimed to evaluate the effect of interferon-alpha therapy on the long-term outcome of HBeAg-negative chronic hepatitis B. METHODS: A cohort of 209 interferon-alpha treated and 195 untreated patients with histologically documented HBeAg-negative chronic hepatitis B were closely followed for a mean of 6 (1-13.5) years. Patients with decompensated liver disease and/or hepatocellular carcinoma at presentation were excluded. RESULTS: Survival and complication (liver decompensation and/or hepatocellular carcinoma) -free survival were significantly worse in patients with compared to those without baseline cirrhosis and in patients older compared to those younger than 45 years (P < 10(-4)). Sustained biochemical remission was achieved in 57 treated patients. Sustained responders had significantly better survival and complication-free survival than non-sustained responders (P = 0.027 and P = 0.019, respectively) or than untreated patients (P = 0.048 and P = 0.012, respectively). Multivariate analysis showed that absence of baseline cirrhosis, younger age, and sustained biochemical remission were independently associated with an improved outcome. CONCLUSION: In patients with HBeAg-negative chronic hepatitis B, sustained biochemical remission induced by interferon-alpha is associated with improved long-term outcome, even in the presence of cirrhosis and old age, both known factors associated with worse survival. Therefore, long-term biochemical remission appears to represent a satisfactory therapeutic target in this setting.     

Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver.

To evaluate indications for new therapies such as liver transplantation and antiviral therapy, survival of histologically proven hepatitis B surface antigen (HBsAg)-positive cirrhosis of the liver was assessed in a cohort of 98 patients followed up for a mean of 4.3 years. The overall survival probability was 92% at 1 year, 79% at 3 years, and 71% at 5 years. Variables significantly associated with the duration of survival were age, serum aspartate aminotransferase levels, presence of esophageal varices, and all five components of the Child-Pugh index (bilirubin, albumin, coagulation factors, ascites, encephalopathy). Multivariate analysis showed that only age, bilirubin, and ascites were independently related to survival. Survival of patients with decompensated cirrhosis (determined by the presence of ascites, jaundice, encephalopathy, and/or a history of variceal bleeding) and those with compensated cirrhosis at 5 years was 14% and 84%, respectively. For patients with compensated liver cirrhosis, hepatitis B e antigen (HBeAg) positivity was also a prognostic factor with a 5-year survival of 72% for HBeAg-positive cirrhosis and 97% for HBeAg-negative cirrhosis; the risk of death was decreased by a factor of 2.2 when HBeAg seroconversion occurred during follow-up. It is concluded that liver transplantation should be considered for patients with decompensated HBsAg-positive liver cirrhosis and antiviral therapy for patients with HBeAg-positive compensated cirrhosis.     

Natural history and prognosis of hepatitis B

The natural history of hepatitis B virus (HBV) infection is complex and variable and is greatly influenced by the age at infection, the level of HBV replication, and host immune status. Chronic HBV infection generally consists of an early replicative phase with active liver disease (hepatitis B e antigen [HBeAg]-positive chronic hepatitis) and a late low or nonreplicative phase with HBeAg seroconversion and remission of liver disease (inactive carrier state). After HBeAg seroconversion, some patients may have active hepatitis due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). Morbidity and mortality are linked to development of cirrhosis and hepatocellular carcinoma. Survival is reasonably good (about 85% probability at 5 years) in compensated cirrhosis but very poor in decompensated cirrhosis. Both cirrhotic and noncirrhotic patients with sustained reduction of HBV replication and normalization of aminotransferase after interferon alfa therapy have a reduced risk for liver-related complications.     

Natural history of hepatitis B

The natural course of hepatitis B virus (HBV) chronic infection is variable, ranging from an inactive HBsAg carrier state to a more or less progressive chronic hepatitis, potentially evolving to cirrhosis and hepatocellular carcinoma (HCC). Chronic hepatitis may present as typical HBeAg-positive chronic hepatitis B or HBeAg-negative chronic hepatitis B. HBeAg-positive chronic hepatitis is due to wild type HBV; it represents the early phase of chronic HBV infection. HBeAg-negative chronic hepatitis is due to a naturally occurring HBV variant with mutations in the precore or/and basic core promoter regions of the genome; it represents a late phase of chronic HBV infection. The latter form of the disease has been recognized as increasing in many countries within the last decade and it represents the majority of cases in many countries. HBeAg-negative chronic hepatitis B is generally associated with a more severe liver disease with a very low rate of spontaneous disease remission and a low sustained response rate to antiviral therapy. Longitudinal studies of patients with chronic hepatitis B indicate that, after diagnosis, the 5-year cumulative incidence of developing cirrhosis ranges from 8-20%. Morbidity and mortality in chronic hepatitis B are linked to evolution to cirrhosis or HCC. The 5-year cumulative incidence of hepatic decompensation is approximately 20%. The 5-year probability of survival is approximately 80-86% in patients with compensated cirrhosis. Patients with decompensated cirrhosis have a poor prognosis (14-35% probability of survival at 5 years). HBV-related end-stage liver disease or HCC are responsible for at least 500,000 deaths per year.     

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.     

Usefulness of non-invasive markers for predicting liver cirrhosis in patients with chronic hepatitis B

Background and Aim:  Recently, various non-invasive blood markers and indices have been studied to overcome the limitations of liver biopsy, such as its invasiveness and sampling errors. However, the majority of these studies have focused on patients with chronic hepatitis C. Accordingly, this study was performed to evaluate the significances of various non-invasive serum markers in terms of predicting the presence of liver cirrhosis in chronic hepatitis B.
Methods:  We included 125 chronic hepatitis B patients who had undergone liver biopsy. Fibrosis stage was assessed using the METAVIR scoring system (F0–F4), which defines liver cirrhosis as F4. In addition, we measured various blood markers at times of liver biopsy.
Results:  Thirty four of the 125 patients (27.2%) were rated as F4 by liver biopsy. Age, platelet, white blood cells, aspartate aminotransferase (AST), alanine aminotransferase, haptoglobin, apolipoprotein-A1 (Apo-A1), collagen-IV, hyaluronic acid, α2-macroglobulin, matrix metalloproteinase-2, and YKL-40 were significantly different between patients with chronic hepatitis and those with liver cirrhosis. However, multivariate analysis showed that only platelet, AST, haptoglobin, and Apo-A1 independently predicted the presence of liver cirrhosis. Having identified these four factors, we devised a system, which we refer to as platelet count, AST, haptoglobin, and Apo-A1 (PAHA). The area under the receiver-operating characteristics (AUROC) of PAHA indices for the presence of liver cirrhosis was 0.924 (95% confidence interval, 0.877–0.971), which was significantly greater than the AUROC of other indices of fibrosis.
Conclusion:  The devised PAHA system was found to be useful for predicting the presence of liver cirrhosis in patients with chronic hepatitis B.     

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.     

Comparison of outcomes between patients with alcoholic cirrhosis and those with hepatitis C virus-related cirrhosis

Background and Aim:  The natural history of alcoholic cirrhosis, especially in Asian countries, has not been completely understood thus far.
Methods:  We retrospectively compared the outcomes of compensated cirrhosis between Japanese alcoholic and hepatitis C virus (HCV)-infected patients.
Results:  A total of 227 patients (75 alcoholic and 152 HCV-infected patients) with compensated cirrhosis were enrolled. The median follow-up period was 4.9 years. The cumulative rates of hepatocellular carcinoma (HCC) development were significantly lower in the alcoholic patients than in the HCV-infected patients (6.8% vs 50.3% at 10 years, P  = 0.0003), while the cumulative rates of hepatic decompensation (37.4% vs 51.7% at 10 years) and survival (53.8% vs 47.4% at 10 years) did not significantly differ between the two groups (Kaplan-Meir analysis). The main causes of death were hepatic failure and non-hepatic diseases in the alcoholic patients and HCC and hepatic failure in the HCV-infected patients. Multivariate analyses using the Cox proportional hazard model revealed that the risk of HCC was lower in alcoholic cirrhosis than in HCV-related cirrhosis (hazard ratio (HR), 0.46), while the risk of hepatic decompensation and mortality was the same. Predictors of decreased survival were non-abstinence (HR, 2.53) in the alcoholic patients and low serum albumin level (1.58) in the HCV-infected patients.
Conclusions:  Survival of patients with alcoholic cirrhosis was similar to that of patients with HCV-related cirrhosis. The risk of HCC development was lower in alcoholic cirrhosis than in HCV-related cirrhosis. Abstinence from alcohol was important for improving the survival of patients with alcoholic cirrhosis.     

Serum hepatitis B virus DNA levels differentiating inactive carriers from patients with chronic hepatitis B

OBJECTIVE: We compared serum hepatitis B virus (HBV)-DNA levels in different states of hepatitis B infection, and investigated whether there is an HBV-DNA value that can be used for differentiating inactive carriers from patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis. METHODS: A retrospective study using sera at a followed endpoint from 64 Japanese patients with chronic HBV infection seen in Kobe University Hospital between 1989 and 2002. Sera of patients were assayed using a polymerase chain reaction-based assay. RESULTS: Genotype C was dominant (95.4%). Patients with chronic hepatitis with an elevation of the serum alanine aminotransferase (ALT) level had significantly higher HBV-DNA levels than patients with persistently normal ALT. For one time observation at a followed endpoint, the mean HBV-DNA level of HBeAg-negative inactive carriers was significantly lower than that of HBeAg-negative chronic hepatitis patients (3.6+/-1.0 versus 4.8+/-1.5 log copies/ml, P<0.005). The use of a cutoff value of 4.5 or 5.0 log copies/ml misclassified 23 and 18% of HBeAg-negative inactive carriers and 50 and 55% of patients with HBeAg-negative chronic hepatitis. If testing were performed on two occasions with approximately a 4-month interval, the cutoff values of 4.5 and 5.0 log copies/ml would misclassify 20 and 10% of HBeAg-negative inactive carriers and 28.6 and 28.6% of patients with HBeAg-negative chronic hepatitis. CONCLUSIONS: The measurement of serum HBV DNA more than twice is useful for assessing chronic hepatitis B surface antigen carriers and confirms that 10 copies/ml may be an appropriate level of HBV for characterizing the inactive carrier state.     

Profile of hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Although chronic hepatitis B occurs in hepatitis B e antigen (HBeAg)-negative patients, its prevalence and clinical significance are not known. AIM: To determine the prevalence and profile of HBeAg-negative chronic hepatitis B virus (HBV) infection. METHODS: A retrospective analysis of 363 consecutive patients (mean age 36 y; 288 men) with chronic HBV infection was performed. All patients were HBsAg-positive. Tests for liver profile, HBeAg and anti-HBe antibody were performed in all patients. Serum HBV DNA was tested using branched DNA assay in 245 patients. The patients were classified into three groups: no cirrhosis with normal ALT levels, no cirrhosis with elevated ALT levels, and clinical or histological evidence of cirrhosis. RESULTS: Of 363 patients, 141 (39%) were HBeAg-positive and 222 (61%) HBeAg-negative. Of HBeAg-negative patients, 120 (54%) had normal ALT, 45 (20%) had elevated ALT and 57 (26%) had evidence of cirrhosis; corresponding figures in the HBeAg-positive patients were 40 (28%), 66 (47%) and 35 (25%). HBV DNA was positive in 53 of 131 (40%) HBeAg-negative patients tested; of these 53 patients, 9 (17%) had normal ALT, 20 (38%) had elevated ALT and 24 (45%) had cirrhosis. Thus, 72% of HBeAg-positive and 46% of HBeAg-negative patients had elevated ALT and/or cirrhosis. Among the latter group, 83% of HBV DNA-positive patients had elevated ALT and/or cirrhosis. Overall, 18% of HBsAg-positive patients had HBeAg-negative, HBV DNA-positive liver disease. CONCLUSION: HBeAg-negative chronic hepatitis B is not an uncommon and benign entity and chronic liver disease develops in a significant proportion of such patients.     

Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea

BACKGROUND/AIMS: The aims of this study were to determine the frequency of precore/core promoter mutations and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Korea. METHODS: Patients with chronic hepatitis B virus (HBV) infection were tested for HBeAg, anti-HBe, liver profile and HBV-DNA by a branched DNA (bDNA) assay. Serum HBV-DNA was amplified by a polymerase chain reaction and the precore/core promoter sequence was determined. RESULTS: Among the 413 consecutive HBeAg-negative patients, 19.6% were bDNA-positive. Evidence of liver disease was found in 90.1% of bDNA-positive and 41.7% of bDNA-negative patients. Overall, 17.7% of HBeAg-negative patients had e-CHB. Precore mutation (A1896) was detected in 93.7% of HBeAg-negative bDNA-positive and 93.9% of HBeAg-negative bDNA-negative patients. In 59 HBeAg-positive patients, 78% had wild-type and 22% had a mixture of wild-type and A1896 mutant. Core promoter TA mutation was detected in 89.9% of HBeAg-negative bDNA-positive patients, 89.8% of HBeAg-negative bDNA-negative patients, and 74.6% of HBeAg-positive patients. No correlation was found between the presence of precore/core promoter mutations and HBV-DNA levels or disease severity. CONCLUSIONS: In Korean patients infected with HBV genotype C, precore mutation occurred almost invariably along with HBeAg seroconversion and core promoter TA mutation was frequent irrespective of viral replication levels or disease severity.     

Hepatitis B e antigen-negative chronic hepatitis B in Hong Kong

Hepatitis B e antigen-negative chronic hepatitis B (e-CHB) has been reported in Asia but its prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of e-CHB in Hong Kong and the frequency of precore and core promoter mutations in these patients. A cross-sectional study was performed in 350 consecutive Chinese patients (230 men and 120 women; mean age +/-SD, 42 +/- 13 years) with chronic hepatitis B virus infection. A total of 243 (69%) patients were hepatitis B e antigen (HBeAg)-negative of whom 15% had clinical cirrhosis. In the remaining 85% of patients, 63% had normal and 22% had elevated transaminases. Serum hepatitis B virus (HBV) DNA was detectable using branched DNA assay in 46% of HBeAg-negative patients with clinical cirrhosis/elevated transaminases. Forty-five percent of the patients with e-CHB had the precore stop codon mutation, and an additional 41% had core promoter changes. There was no correlation between the presence of precore/core promoter mutations and liver disease or HBV-DNA levels. Overall, 17% of HBeAg-negative patients were viremic and had evidence of chronic liver disease (e-CHB) with mean HBV-DNA levels comparable with that in HBeAg-positive patients. In summary, we found that e-CHB may be present in up to 17% of HBeAg-negative patients seen in a tertiary referral center in Hong Kong. e-CHB may be a heterogeneous condition and is not invariably associated with the precore HBV mutant. Population studies are needed to determine the true prevalence of e-CHB in Asia and to assess its natural course and response to treatment.     

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.     

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.     

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.