Evaluation of changes of serum hepatitis B surface antigen from a different perspective.

AIM: To investigate the dynamic changes of serum hepatitis B surface antigen (HBsAg) levels apportioned by the same hepatic parenchyma cell volume (HPCV), namely, hepatic cell quantities. METHODS: Serum HBsAg levels were detected by electrochemiluminescence and serum HBsAg levels apportioned by the same HPCV were figured out according to the theory of sphere geometry. HBsAg levels were compared among different liver inflammation grades, as well as different hepatic fibrosis stages. RESULTS: In hepatitis B e antigen-negative chronic hepatitis B, serum HBsAg levels in liver histological inflammation grades 1-4 were 3.66 ± 0.40, 3.74 ± 0.35, 3.74 ± 0.26 and 3.71 ± 0.34 log10 COI (cut off index), respectively, and there were no differences before apportion (P = 0.640). Serum HBsAg levels apportioned by the same HPCV were 5.57 ± 0.62, 5.98 ± 0.65, 6.59 ± 0.50 and 6.81 ± 0.84 log10 COI, respectively, and there were significant differences after apportion (P < 0.001). Serum HBsAg levels in hepatic fibrosis stages I-IV were 3.66 ± 0.43, 3.75 ± 0.33, 3.71 ± 0.28 and 3.75 ± 0.26 log10 COI, respectively, and there were no differences before apportion (P = 0.513). Serum HBsAg levels apportioned by the same HPCV were 5.53 ± 0.66, 5.98 ± 0.53, 6.29 ± 0.46 and 7.06 ± 0.48 log10 COI, respectively, and there were significant differences after apportion (P < 0.001). CONCLUSION: Serum HBsAg levels apportioned by the same HPCV (hepatic cell quantities), rather than serum HBsAg levels, increase with liver inflammation grades and hepatic fibrosis stages.

Serum HBsAg level and its clinical significance in lamivudine treatment for patients with HBeAg-negative acute-on-chronic liver failure.

OBJECTIVES: To investigate the dynamics and clinical significance of hepatitis B surface antigen (HBsAg) levels in hepatitis B e antigen (HBeAg)-negative acute-on-chronic liver failure (ACLF) patients receiving lamivudine. METHODS: Fifty-nine nucleoside-naïve patients with HBeAg-negative ACLF were enrolled and treated with 100mg of lamivudine daily. The dynamics of serum levels of HBsAg and HBV DNA were analyzed at baseline and at week 12, or before death if the patient died within 12 weeks. RESULTS: Twenty-eight cases died within 12 weeks and 31 cases survived after treatment. HBsAg levels of patients who survived were significantly higher than those of patients who died both pre- and post-treatment (all p<0.05). There were 33 patients with pretreatment HBsAg levels above 4000 COI and 26 cases with levels below this value. The 12-week survival rate of those with levels ≥4000 COI was significantly higher than that of patients with levels <4000 COI (66.7% (22/33) vs. 34.5% (9/26), Chi-square = 5.991, p=0.014). Regardless of the pretreatment HBsAg level, there was no significant difference in HBV DNA levels between survivors and those who died, and no correlation was observed between HBV DNA and HBsAg (all P>0.05). CONCLUSIONS: Changes in HBsAg level could be a useful parameter for predicting the short-term outcome of lamivudine monotherapy in HBeAg-negative ACLF.

Pretreatment HBsAg level and an early decrease in MELD score predict prognosis to lamivudine treatment for HBeAg-negative acute-on-chronic liver failure.

BACKGROUND AND OBJECTIVE: Few data are available about the predictability of HBsAg quantification to nucleos(t)ide analogues treatment in acute-on-chronic liver failure (ACLF). The aim of this study was to investigate HBsAg level combined with the model for end-stage liver disease (MELD) score for predicting prognosis to lamivudine monotherapy in HBeAg-negative ACLF. METHODS: Fifty-seven nucleoside-naïve patients with HBeAg-negative ACLF were treated with 100mg of lamivudine daily. Serum levels of HBsAg, HBV DNA and biochemical items were detected at baseline, before death (patients died within 3months) or month 3 meanwhile MELD score was calculated. Dynamic of these items and 3-month mortality were analyzed. RESULTS: HBV DNA level significantly decreased while HBsAg level did not after treatment. Twenty-six patients died within 3months and the others survived. Regardless pre- or post-treatment, HBsAg level of survival group was significantly higher than that of dead group meanwhile MELD scores of the former were significantly lower than those of the latter (all P<0.05). Post-treatment MELD scores of 32 patients with pretreatment HBsAg levels above 4000 COI were significantly lower than those of 25 patients below to it (t=-2.116, P=0.044) and the 3-month mortality of the formers was significantly lower than that of the latter (34.3% [11/32] vs 64.0% [16/25], χ(2)=4.941, P=0.026). CONCLUSIONS: In HBeAg-negative ACLF, patient with higher pretreatment HBsAg levels and early decrease in MELD score has lower 3-month mortality than one without it during lamivudine monotherapy.

Influence of chronic HBV infection on superimposed acute hepatitis E.

AIM: To investigate the influence of chronic hepatitis B virus (HBV) infection [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on superimposed acute hepatitis E. METHODS: A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University, from January 2003 to January 2012. The patients were classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and an HEV group (a group with acute hepatitis E, n = 176). We retrospectively analyzed and compared the clinical features of the two groups. Statistical analyses were performed using the χ(2) test or Fisher's exact test for categorical variables and the Student's t test for continuous variables. A P value < 0.05 was considered statistically significant. RESULTS: The peak values of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease scores were significantly higher in the HBV + HEV group. More patients in the HBV + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of the HBV + HEV group showed that there were no significant differences in complication occurrence, liver failure incidence, or mortality between patients with different HBeAg and HBV DNA statuses. However, in patients with underlying cirrhosis, complication occurrence and liver failure incidence significantly increased. In total, 12.7% of the patients in the HBV + HEV group received anti-HBV treatment, but this therapy failed to reduce mortality in patients who developed liver failure. CONCLUSION: The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.

[Dynamic change of hepatitis B surface antigen expression in chronic hepatitis B patients during the natural recovery course and the short-term antivirus treatment].

OBJECTIVE: To investigate the dynamic quantitative changes in expression of hepatitis B virus (HBV) surface antigen (HBsAg) that occurs during the natural recovery course and the short-term antivirus treatment period of patients suffering from flares in chronic hepatitis B (CHB). METHODS: CHB patients presenting for treatment of flare-ups were randomly assigned to receive treatment with Entecavir antiviral (group A, n = 39) or to naturally resolve the acute condition (group B, n = 22). All patients MELD scores were calculated and HBsAg levels and HBV DNA loads were measured upon admission (baseline), at worst-condition stage, and end of treatment/flare-up (discharge). Pairwise comparisons of intergroup differences were made to evaluate the change in the three disease parameters over time in response to the management approach. RESULTS: The levels of HBsAg were not significantly different between the two groups at baseline, worst-condition stage and discharge (group A: (3.68+/-0.45), (3.84+/-0.19) and (3.69+/-0.58) log10 cut-off index (COI) respectively; group B: (3.59+/-0.54), (3.47+/-0.76) and (3.43+/-0.68) log10 COI respectively; all P more than 0.05). However, the HBV DNA loads were significantly lower in group A than in group B at the worst-condition stage and at discharge (all P less than 0.05). In group A, the MELD scores were significantly higher at baseline and at worst-condition stage than at discharge (all P = 0.000), but the difference between baseline and worst-condition stage was not significant. Also in group A, the HBV DNA load showed a gradually decreasing trend over time (baseline more than worst-condition stage more than discharge, all P less than 0.05). No significant differences were observed over time in the HBsAg levels of group A. In group B, the MELD scores were significantly higher at baseline and at worst-condition stage than at discharge (all P = 0.000), but the difference between baseline and worst-condition stage was not significant (P = 0.619). Also in group B, the HBV DNA loads were significantly higher at baseline and worst-condition stage than at discharge (P = 0.000 and P = 0.003 respectively), but the difference between baseline and worst-condition stage was not significant. Finally, no significant differences were observed over time in the HBsAg levels of group B. CONCLUSION: Natural recovery from an acute flare-up of CHB is not accompanied by a change in HBsAg levels. In addition, short-term antiviral treatment to resolve the flare-up has no influence on HBsAg level.

Short-term entecavir versus lamivudine therapy for HBeAg-negative patients with acute-on-chronic hepatitis B liver failure.

BACKGROUND: Selection of drugs for antiviral therapy of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains difficult. This study was undertaken to evaluate the short-term efficacy of entecavir versus lamivudine on hepatitis B e antigen (HBeAg)-negative patients with ACLF. METHODS: The data of 182 HBeAg-negative patients with ACLF were retrospectively collected from patient profiles of the hospital. In these patients, 93 HBeAg-negative patients with ACLF were treated orally with 0.5 mg of entecavir and 89 were treated orally with 100 mg of lamivudine every day. The gender and age were matched between the two groups. Biochemical items, the model for end-stage liver disease (MELD) score, and HBV DNA level were matched at baseline between the two groups and monitored during treatment. The 3-month mortalities of the two groups were compared. RESULTS: No significant differences were found in biochemical items, MELD score, and HBV DNA level at baseline (P>0.05). HBV DNA level decreased within 3 months in both groups (P<0.05), regardless of the pretreatment MELD score. In patients with the same range of pretreatment MELD scores, treatment duration, posttreatment HBV DNA levels, percentage of HBV DNA level <2.7 lg copies/mL, biochemical items, MELD scores and 3-month mortality were similar in the two groups (all P>0.05). Pretreatment MELD score was not related to posttreatment HBV DNA levels (P>0.05), but related to a 3-month mortality in both groups (both P<0.001). CONCLUSIONS: In HBeAg-negative patients with ACLF, the short-term efficacy of entecavir versus lamivudine was similar. The degree of pretreatment liver failure significantly affected the outcome of treatment.

[To investigate the opportunity of entecavir treatment for HBeAg-negative acute-on-chronic liver].

OBJECTIVE: To explore relations between the opportunities and effects of internal general treatment added Entecavir on acute-on-chronic liver failure (ACLF) of HBeAg-negative chronic hepatitis B in different score ranges of acute-on-chronic liver failure severity. METHODS: A total of 108 ACLF of HBeAg-negative chronic hepatitis B patients with different ACLF severity score were treated with internal general treatment added Entecavir. The liver failure severity scores, HBV-DNA loads during the initiation of therapy, recovery phase and in deathbed phase, courses of Entecavir administration and mortalities were studied. RESULTS: For 19 patients with high ACLF score (> or = 12), the difference in ACLF score between pre and post-treatment was not significant. The difference in HBV-DNA load between pre and post-treatment was not significant and the mortality was 18/19. For 30 patients with higher intermediate ACLF score (8-11), the difference in ACLF score between pre and post-treatment was not significant. The difference in HBV-DNA load between pre and post-treatment was significant, and the mortality was 66.67% (20/30). For 36 patients with lower intermediate ACLF score (5-7), the difference in ACLF score between pre and posttreatment was not significant. The difference in HBV-DNA load between pre and post-treatment was significant, and the mortality was 30.56% (11/36). For 23 patients with low ACLF score (< or = 4), the difference in ACLF score between pre and post-treatment was significant. The difference in HBV-DNA load between pre and post-treatment was significant, and the mortality was 8.70% (2/23). CONCLUSIONS: A novel acute-on-chronic liver failure scoring system can syllabify differentiate the relations between the opportunities and efficacies on the Entecavir treatment for HBeAg-negative ACLF.

[Dynamic expression profile of HBsAg according to hepatic parenchyma cells' volume at different liver fibrosis stages in the immune clearance phase].

The aim of this study was to determine the dynamic expression profile of hepatitis B surface antigen (HBsAg) according to hepatic parenchyma cells' volume at different stages of liver fibrosis during the immune clearance phase. Eighty-nine patients with HBeAg-positive chronic hepatitis B (CHB) in the immune clearance stage were recruited for study. Each patient's serum HBsAg levels were detected by electrochemiluminescence. The serum HBsAg levels were apportioned according to hepatic parenchyma cells' volume at liver fibrosis stages 1, 2, 3, and 4 and compared by ANOVA. The unapportioned serum HBsAg levels (IU/mL) at liver fibrosis stages 1 (227.2+/-237.7), 2 (211.0+/-131.4), 3(300.1+/-144.6), and 4 (278.7+/-148.8) were not significantly different (all comparisons, P range: 0.061 to 0.759). However, when the serum HBsAg levels were apportioned by the same hepatic parenchyma cells' volume at liver fibrosis stages 1 (343.9+/-359.8), 2 (336.4+/-209.5), 3 (508.7+/-245.1), and 4 (525.2+/-274.8), the levels were significantly different (all comparisons, F = 3.045 and P = 0.033; stage 1 vs. 3, P = 0.041; stage 1 vs. 4, P = 0.046; stage 2 vs. 3, P = 0.028; stage 2 vs. 4, P = 0.034). During the immune clearance phase of chronic hepatitis B, increased HBsAg expression is associated with increased hepatic parenchyma cells' volume and progressive liver fibrosis stage.

[Dynamics of serum HBV DNA levels during the terminal phases of acute-on-chronic hepatitis B liver failure with different HBeAg status].

OBJECTIVE: To investigate the dynamics and clinical significance of serum hepatitis B virus (HBV) DNA levels during the terminal phase of acute-on-chronic liver failure (ACLF) with different hepatitis B e antigen (HBeAg) status. METHODS: One-hundred-and-seven patients with terminal ACLF were tested for HBeAg status by electrochemiluminescence immunoassay and serum HBV DNA levels by real-time PCR at three chronological time ranges, representing increasing severity of disease phases prior to death (day 0): 29-56 d, 15-28 d, and 0-14 d. RESULTS: In the 37 HBeAg(+) patients, HBV DNA levels at above-mentioned phases were 6.10+/-1.63, 5.61+/-1.50, and 5.29+/-1.96 log10 copies/mL. In the 70 anti-HBe(+) patients, HBV DNA levels were 4.63+/-1.82, 5.81+/-1.78, and 4.93+/-1.73 log10 copies/mL. Phase to phase comparisons revealed that the HBV DNA level in the HBeAg(+) group was significantly higher than that in the anti-HBe(+) group at 29-56 d (P less than 0.05), and that 15-28 d and 0-14 d were not significantly different (P more than 0.05). Intragroup comparisons of phases revealed no significant differences in the HBeAg(+) group (P more than 0.05), but a significant difference between 15-28 d and 0-14 d (P less than 0.05) for the anti-HBe(+) group. CONCLUSION: Serum levels of HBV DNA in patients with HBeAg positivity are higher than those in patients with anti-HBe positivity as the disease phase of ACLF nears fatality. Following the deterioration to liver failure, the HBV DNA load in HBeAg(+) patients remains stable while that in anti-HBe(+) patients decreases.

What MELD score mandates use of entecavir for ACLF-HBV HBeAg-negative patients?

AIM: To investigate optimal timing for therapeutic efficacy of entecavir for acute-on-chronic hepatitis B liver failure (ACLF-HBV) in hepatitis B e antigen (HBeAg)-negative patients. METHODS: A total of 109 inpatients with ACLF-HBV were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University from October 2007 to October 2010. Entecavir 0.5 mg/d was added to each patient's comprehensive therapeutic regimen. Patients were divided into three groups according to model for end-stage liver disease (MELD) score: high (≥ 30, 20 males and 4 females, mean age 47.8 ± 13.5 years); intermediate (22-30, 49 males and 5 females, 45.9 ± 12.4 years); and low (≤ 22, 28 males and 3 females, 43.4 ± 9.4 years). Statistical analysis were performed using SPSS 11.0 software. Data with normal distribution were expressed as mean ± SD and comparisons were made with Student's t tests. A value of P < 0.05 was considered statistically significant. Viral loads were related exponentially and logarithmic data were used for analysis. RESULTS: For 24 patients with MELD score ≥ 30, treatment lasted 17.2 ± 16.5 d. Scores before and after treatment were significantly different (35.97 ± 4.87 and 40.48 ± 8.17, respectively, t = -2.762, P = 0.011); HBV DNA load was reduced (4.882 ± 1.847 copies log(10)/mL to 3.685 ± 1.436 copies log(10)/mL); and mortality rate was 95.83% (23/24). Of 54 patients with scores of 22-30, treatment lasted for 54.0 ± 43.2 d; scores before and after treatment were 25.87 ± 2.33 and 25.82 ± 13.92, respectively (t = -0.030, P = 0.976); HBV DNA load decreased from 6.308 ± 1.607 to 3.473 ± 2.097 copies log(10)/mL; and mortality was 51.85% (28/54). Of 31 patients with scores ≤ 22, treatment lasted for 66.1 ± 41.9 d; scores before and after treatment were 18.88 ± 2.44 and 12.39 ± 7.80, respectively, (t = 4.860, P = 0.000); HBV DNA load decreased from 5.841 ± 1.734 to 2.657 ± 1.154 copies log(10)/mL; and mortality was 3.23% (1/31). CONCLUSION: For HBeAg-negative patients with ACLF-HBV, when entecavir was added to comprehensive therapy, a MELD score ≥ 30 predicted very poor prognosis due to fatal liver failure.

[The relationship of HBeAg status with HBV DNA loads, MELD scores in patients with acute-on-chronic hepatitis B liver failure during terminal phases].

OBJECTIVE: To investigate the relationship and clinical significances of HBeAg status with serum HBV DNA loads, model for end-stage liver disease (MELD) scores in patients with acute-on-chronic hepatitis B liver failure during terminal phase. METHODS: 120 fatal patients were enrolled. At three phases of 0 -14 d, 15-28 d and 29-90 d before death, they were detected serum HBeAg, HBV DNA loads order meanwhile MELD scores were calculated. RESULTS: In 51 patients with HBeAg positive, HBV DNA levels were (5.25 +/- 1.99), (5.45 +/- 1.47) and (6.06 +/- 1.77) log10 copies/ml while MELD scores were (30.33 +/- 5.25), (26.36 +/- 6.43) and (20.13 +/- 6.47) respectively. In 69 patients with HBeAg negative,HBV DNA loads were (5.14 +/- 1.84), (5.49 +/- 1.75 ) and (4.62 +/- 1.65) log10 copies/ml while MELD scores were 32.38 +/- 9.95, 28.17 +/- 6.82 and 26.19 +/- 5.56 in sequence. Compared with the same phase between HBeAg-positive group and HBeAg-negative group, significant differences in both HBV DNA loads and MELD scores were found only at the phase of 29-90 d (P < 0.05). In multiple comparisons among three phases, regardless of the HBeAg status,there wasn't significant difference for HBV DNA loads (P > 0.05). But increasing MELD scores are associated with the disease exacerbation and significant differences were found (P < 0.05). CONCLUSIONS: To initiate acute-on-chronic hepatitis B liver failure, serum HBV DNA loads of HBeAg-positive patients are higher than that of HBeAg-negative ones. Once ACLF has been initiated,sustained high HBV DNA loads may promote the disease worsened and be fatal regardless of the HBeAg status.

Development of a sensitive prognostic scoring system for the evaluation of severity of acute-on-chronic hepatitis B liver failure: a retrospective cohort study.

PURPOSE: The purpose of the current study was to establish an objective, simple, and sensitive prognostic scoring system for estimating the severity of acute-on-chronic liver failure in hepatitis B (ACLFB). METHODS: A novel prognostic scoring system was calculated from six clinical indices including total bilirubin (TB), prothrombin activity (PTA), creatinine (Cr), hepatic encephalopathy (HE), infections, and the depth of ascites from 726 patients with ACLFB. Indices were scored from 1 to 4 according to their severity. Groups of the same patients were scored with three-indices (TB, PTA and Cr), four-indices (TB, PTA, Cr and HE), five-indices (TB, PTA, Cr, HE and the depth of ascites) or six-indices (TB, PTA, Cr, HE, the depth of ascites, and infections). The differences in the sensitivity and specificity of four scoring systems were analyzed. RESULTS: The demarcation points of the three-, four-, five- and six-indices scoring systems were 4.62, 6.12, 7.88 and 9.57, respectively. The analysis of the areas under the receiver operating characteristic (ROC) curve indicated that the four-, five- and six-indices scoring systems were more exact, and objective than the three-indices prognostic scoring system. In the six-indices scoring system, the survival rates of patients with scores from 2 to 6 was 98.31% (233/237), and the mortality rate of patients with scores of 16 and above was 100.00% (140/140), while the mortality rates were 8.33% (3/36) and 96.43% (27/28) for those with scores from 7 to 15, respectively. CONCLUSION: A six-indices scoring system is an objective, pertinent, and sensitive system, and may be useful for the prognostic evaluation of ACLFB.

A Novel prognostic scoring system to predict 3-month mortality risk in patients with acute-on-chronic liver failure in hepatitis B: a retrospective cohort study.

PURPOSE: The present study was done to establish an objective, sensitive prognostic scoring system and to determine the applicability of this model in predicting the 3-month mortality of patients with acute-on-chronic liver failure in hepatitis B (ACLFB). METHODS: We developed a novel prognostic scoring system, calculated from six clinical indices including serum total bilirubin, prothrombin activity, serum creatinine, hepatic encephalopathy, infections, and the depth of ascites from 499 patients with ACLFB. Differences in the sensitivity, specificity, and practicality of a Novel prognostic scoring system and the model of end-stage liver disease (MELD) were analyzed. RESULTS: The areas under the receiver operating characteristic curve (ROC) for the Novel scoring systems and MELD scoring systems were 0.967 (95% CI, 0.956-0.977) and 0.900 (95% CI, 0.878-0.922), respectively. The analysis of the ROC curve indicated that the Novel scoring systems were an exact, pertinent, and objective prognostic model with greater accuracy than the MELD. In the Novel scoring systems, the survival rate of these patients whose scores ranged from 2 to 6 was 98.80%, while for those whose scores point at 7 and 15, the mortality rates were 8.70% (2/23) and 95.45% (21/22), respectively, and the mortality rate of these patients whose scores were 16 and above was 100.00%. However, in the MELD prognostic scoring systems, there were no score ranges with 100.00% survival rate. CONCLUSIONS: We developed an objective, pertinent, and sensitive prognostic scoring system that predicted the 3-month mortality of patients with ACLFB with greater accuracy than the MELD.

Collagen proportionate area of liver tissue determined by digital image analysis in patients with HBV-related decompensated cirrhosis.

BACKGROUND: The accurate assessment of the degree of hepatic fibrosis plays a critical role in guiding the diagnosis, treatment and prognostic assessment of chronic liver diseases. Liver biopsy is currently the most reliable method to evaluate the severity of hepatic fibrosis. However, liver biopsy is an invasive procedure associated with morbidity and mortality, and has several limitations in patients with decompensated cirrhosis. There is no report on the collagen proportionate area (CPA) of liver tissue in the decompensated stage of cirrhosis. This study aimed to determine the CPA of resected liver tissue samples from patients with HBV-related decompensated cirrhosis using digital image analysis, and to analyze the relationship between the CPA and liver functional reserve. METHODS: Fifty-three resected liver tissue samples from liver transplant patients with chronic hepatitis B-induced decompensated cirrhosis were stained with Masson's trichrome, and the CPA in these samples was quantitatively determined using digital image analysis. The values of relevant liver function just before liver transplantation, the CPA in liver tissue, and their correlation were analyzed. RESULTS: The mean CPA at the decompensated stage of cirrhosis was 35.93+/-14.42% (11.24%-63.41%). The correlation coefficients of the CPA with a model for end-stage liver disease score, serum total bilirubin and international standard ratio of prothrombin B were 0.553, 0.519 and 0.533, respectively (P<0.001). With increasing CPA values, the three indices reflecting liver functional reserve also changed significantly. CONCLUSIONS: The degree of fibrosis may be correlated with the functional reserve. With the advancement of fibrosis, the liver functional reserve is attenuated accordingly.

[Discussion on the meaning of MELD score in the opportunity of the entecavir treatment of HBeAg-negative acute-on-chronic liver failure].

OBJECTIVE: To explore the opportunity and effect of internal general treatment added entecavir on acute-on-chronic liver failure (ACLF) of HBeAg-negative chronic hepatitis B patients in different ranges of MELD score. METHODS: A total of 101 ACLF of HBeAg-negative chronic hepatitis B patients treated with internal general treatment added entecavir were divided into three groups according to the MELD score. The mortalities and HBV DNA loads during the initiation of therapy, recovery phase and in deathbed phase were studied. RESULTS: 20 of patients with high MELD score (> or = 30) received (14.6 +/- 14.1) days treatment. The difference in MELD score between pre-(36.03 +/- 5.01) and post-treatment (39.86 +/- 5.95) was significant (t = - 2.994, P = 0.007). There was no significant difference in HBV DNA load between pre-[(4.454 +/- 1.714) copies log10/ml] and post-treatment [(3.979 +/- 1.947) copies log10/ml] (t = 2.212, P = 0.051), the mortality was 100% (20/20). 47 of patients with moderate MELD score (22-30) received (51.5 +/- 41.6) days treatment. There was no significant difference in MELD score between pre-(25.71 +/- 2.47) and post-treatment (26.18 +/- 13.32) (t = - 0.263, P = 0.794). The difference in MELD score between pre-[(6.084 +/- 1.795) copies log10/ml] and post-treatment [(3.378 +/- 2.156) copies log10/ml] was significant (t =7.148, P = 0.000), the mortality was 53.19% (25/47). 34 of patients with low MELD score (< or = 22) received (67.2 +/- 40.9) days treatment. The difference in MELD score was significant between pre-(< or = 18.85 +/- 2.72) and post-treatment (11.68 +/- 7.23) (t = 5.983, P = 0.000). There was significant difference in HBV DNA load between pre-[(5. 945 +/- 1.635) copies log10/ml] and post-treatment [(2.725 +/- 1.194) copies log10/ml] (t = 9.962, P = 0.000), the mortality was 2.94% (1/34). CONCLUSIONS: The ACLF of HBeAg-negative chronic hepatitis B patients with a low score of MELD score (< or = 22) mostly survive with internal general treatment added entecavir. The mortality of the patients with a MELD score (22-30) is 53.19% (25/47). The patients with high MELD score (> or = 30) which almost lack the opportunity of treatment, is associated with fatal liver failure and need for emergency liver transplantation.

[Association between the serum HBV DNA loads normalized to hepatic parenchyma cell volume and the liver histopathologic inflammation gradings in the immune clearance phase].

OBJECTIVE: To investigate the relationship between the serum HBV DNA loads normalized to hepatic parenchyma cell volume and the liver histopathologic inflammation gradings in the immune clearance phase during the natural history of hepatitis B. METHODS: Serum HBV DNA loads were detected by fluorescence polymerase chain reaction and normalized to hepatic parenchyma cell volume. The association between normalized HBV DNA loads and liver inflammation histopathologic grade were analyzed. RESULTS: The serum HBV DNA loads in patients with liver inflammation histopathologic grading 1, 2, 3 and 4 were 8.20*10(5)+/-9.11*10, 1.36*10(6)+/-5.96*10, 8.12*10(5)+/-8.01*10 and 2.08*10(6)+/-3.69*10 copies/ml, respectively (P more than 0.05). But the serum HBV DNA loads normalized to hepatic parenchyma cell volume in their located fibrosis stage were 9.24*10(8)+/-935, 5.33*10(9)+/-756, 1.06*10(10)+/-1770 and 3.31*10(11)+/-518 copies/ml, respectively (P less than 0.05). CONCLUSION: The serum HBV DNA load normalized to hepatic parenchyma cell volume in patients with different fibrosis stages is associated with liver histopathologic inflammation gradings.

[Correlation of genetic polymorphisms of beta-catenin to hepatitis B virus-related hepatocellular carcinoma].

BACKGROUND AND OBJECTIVE: Wnt signaling pathway plays an important role in the carcinogenesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). beta-catenin protein is a pivotal regulator in the pathway. Genetic mutation has been observed in the codons 32-45 at exon 3 of beta-catenin gene in HCC tissues. This study was to investigate the correlation of genetic polymorphisms of beta-catenin to HBV-related HCC. METHODS: We conducted epidemiologic and genetic investigation in 162 patients with HBV-related HCC. According to matching requirements, patients with or without family history of HCC were paired with a ratio of 1:1. Exon 3 of beta-catenin gene was detected by polymerase chain reaction (PCR) and DNA sequencing. Single nucleotide polymorphism (SNP) rs28931588, rs28931589, codons 31-46 sequences and genetic investigation were analyzed. RESULTS: Among the 162 HCC patients, 16 (9.88%) had family history of HCC; 12 patients with family history of HCC and 12 without family history were matched. The 24 patients all showed G on rs28931588 and rs28931589. Three patients showed mutation in codons 32-46 and had genetic polymorphisms. Definite mutational regularity or characteristic mutational site was not observed. CONCLUSION: SNP rs28931588, rs28931589 and codons 31-46 sequences may not be the genetic markers in HBV-related HCC.

[A simple scoring system to evaluate the severity of acute-on-chronic liver failure in hepatitis B].

OBJECTIVE: To establish an objective, simple and sensitive scoring system to evaluate the severity of acute-on-chronic liver failure in hepatitis B. METHODS: The clinical data of patients (194 survivals and 215 deaths) with acute-on-chronic liver failure in hepatitis B were collected and analyzed prospectively. 7 clinical indexes, including the hepatic encephalopathy, creatinine, prothrombin activity, serum total bilirubin, infection, the dimension of liver, the maximum depth of ascites, were scored objectively and simply from 0 to 4 points according to their severity. Then we calculated every patient's total score and divided the 409 patients into two groups: the one was 309 patients and the other is 100 patients. The first group was to establish the severity scoring system and define the cut-off-point, the second group was to test the severity scoring system. RESULTS: The total score of the 144 patients in the survival group was 6.9 +/- 3.2, 165 patients in the dead group was 15.8 +/- 4.0, respectively. There were significant differences (P < 0.01) between the two groups. The area under ROC curve was 0.953. The cut-off-point is 9.5. The sensitivity was 0.97, the specificity was 0.82. The second group patients' total score were divided into two groups: the one is > or = 10 score and the other is < or = 9 score. The prognosis of the first group was much worse than the second group, it's mortality rate was 87.5%; the second was 2.3%. There were significant differences between the two groups (P < 0.01). CONCLUSIONS: This scoring system was simple, sensitive and objective to evaluate the severity of acute-on-chronic liver failure in hepatitis B.

Decline of serum HBV DNA and no change apportioned by the same hepatic parenchyma cell volume from hepatic fibrosis stage 1 to stage 4 during the natural history of chronic hepatitis B.

During the initial phase of chronic hepatitis B virus (HBV) infection, serum HBV DNA levels are high. Contrarily, fibrosis, cirrhosis and hepatocellular carcinoma have been found in patients with lower serum HBV DNA levels. The aim of this study is to clarify HBV DNA level dynamics of serum apportioned by the same hepatic parenchyma cell volume (HPCV) in hepatic fibrosis stages 1-4 during the natural history of chronic hepatitis B. Serum HBV DNA levels were evaluated by real-time polymerase chain reaction. Further, serum HBV DNA levels were apportioned by and compared with the same HPCV in hepatic fibrosis stages 1-4, respectively. Serum HBV DNA levels were 8.91 x 10(6) +/- 4.37 x 10(1), 8.13 x 10(6) +/- 7.41 x 10(1), 9.55 x 10(5) +/- 1.02 x 10(2), and 4.07 x 10(5) +/- 7.24 x 10(1) copies/ml, respectively; there were differences among hepatic fibrosis stages 1-4 (p < 0.021-0.000). However, serum HBV DNA levels apportioned by the same volume of hepatic parenchyma cells in hepatic fibrosis stages 1-4 were 3.47 x 10(10) +/- 8.71 x 10(2), 1.02 x 10(11) +/- 9.55 x 10(2), 1.41 x 10(10) +/- 2.57 x 10(3), and 3.72 x 10(10) +/- 3.02 x 10(3) with HPCV proportions 65.9, 62.7, 58.9, and 53.3%, respectively; there were no differences among hepatic fibrosis stages 1-4 (p > 0.203-0.967).Following the progression of hepatic fibrosis from stage 1 to 4, ongoing decline of HPCV is responsible for a declining trend of serum HBV DNA levels.