Yuan-Jen Wang

Analysis of clinical, biochemical and viral factors associated with early relapse after lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B patients in Taiwan.

Summary.  The efficacy of lamivudine for HBeAg‐negative chronic hepatitis B (CHB) Chinese patients has not been fully investigated. The role of the Hepatitis B virus (HBV) genotype on the treatment effect of lamivudine is controversial. Thirty‐two consecutive patients with HBeAg‐negative CHB were enrolled. All patients were treated with lamivudine 100 mg once daily of 7–12 months duration. The mean total period of follow‐up since entry for all patients was 24 ± 3.5 months. HBV genotypes were classified by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and verified by sequencing. Precore (G1896A) and basic core promoter (BCP, A1762T & G1764A) mutations were determined by PCR and direct sequencing. Twenty‐one (65.6%) patients were infected by genotype B and, 11 (34.4%) by genotype C. G1896A was predominant in genotype B infected patients (95.2%vs 63.6%, P = 0.037). At the end of treatment, 31 (96.8%) and 14 (43.8%) patients achieved biochemical and virological responses, respectively. The biochemical and virological response rates were 40.6 and 0% at 12 months after treatment. Eighteen (56.3%) patients had biochemical relapse within 12 months after withdrawal of lamivudine. By multivariate analysis, the pretreatment serum level of HBV DNA ≥12 Meq/mL was the only factor associated with early biochemical relapse (Odds ratio = 9.333, 95% CI = 1.497 ∼ 58.197, P = 0.017). In conclusion, the virological effect of lamivudine for HBeAg‐negative CHB is transient. Most patients had biochemical relapse within 12 months after lamivudine treatment regardless of HBV genotype. A high pretreatment viral load is the determinant for early biochemical relapse.

Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up.

Background Although many studies have attempted to clarify the association between hepatitis B virus (HBV) infection and fatty liver disease, no prior studies have emphasized the relationship of HBV and fatty liver regarding different demographics of age and body mass index (BMI). Aim To investigate the correlation of HBV and fatty liver in the different demographics of age and BMI. Methods We enrolled consecutive subjects who had received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009 and ultrasonography was used to diagnose fatty liver according to the practice guidelines of the American Gastroenterological Association. Results Among the 33,439 subjects enrolled in this study, fatty liver was diagnosed in 43.9% of the population and 38.9% of patients with chronic HBV infection. Multivariate analysis showed that BMI, age, waist circumference, systolic blood pressure, fasting glucose, cholesterol, alanine aminotransferase (ALT) levels, and platelet counts were positively associated, while hepatitis B surface antigen (HBsAg) positivity was inversely associated with fatty liver, especially for subjects with BMI>22.4 kg/m2 and age>50 years. On the contrary, HBV infection was positively correlated with the presence of elevated serum ALT levels in subjects with fatty liver disease regardless of their age and BMI. Conclusions Metabolic factors are important determinants for the prevalence of fatty liver. Patients with HBV infection were inversely associated with fatty liver disease than the general population, especially in older and obese patients. Furthermore, metabolic factors and HBV infection were associated with elevated serum ALT levels in fatty liver disease.

Long-term follow-up of hepatitis A vaccination in children

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.

Patients with nonalcoholic fatty liver disease have higher risk of colorectal adenoma after negative baseline colonoscopy.

The study aimed to determine whether nonalcoholic fatty liver disease (NAFLD) is an independent risk factor of adenoma after negative baseline colonoscopy.

Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C

Background and Aims: The clinical outcomes of adult‐acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness.

A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.

Durability of Nucleos(t)ide Analogues Treatment in Patients With Chronic Hepatitis B

AbstractLong-term nucleos(t)ide analogues (NUCs) treatment is usually required for patients with chronic hepatitis B (CHB). However, whether discontinuation of NUCs is possible in selected patients remains debated. The aim of this study was to assess the durability of NUCs and predictors of sustained response after cessation of NUCs.Ninety-three CHB patients (29 HBeAg-positive and 64 HBeAg-negative) from 2 medical centers in Taiwan with discontinuation of NUCs after a median of 3 years’ treatment were retrospectively reviewed. Fifteen (51.7%) HBeAg-positive and 57 (89.1%) HBeAg-negative patients achieved APASL treatment endpoints. Virological relapse (VR) and clinical relapse (CR) were defined according to APASL guidelines.Achieving APASL endpoint was associated with longer median time to CR in HBeAg-positive patients, but not in HBeAg-negative cases. The cumulative 1-year VR and CR rates were 55.3% and 14.4% in HBeAg-positive patients, and 77.7% and 41.9% in HBeAg-negative patients, respectively. In HBeAg-negative patients, baseline HBV DNA >105 IU/mL was the only predictor of VR (hazard ratio [HR] = 2.277, P = 0.019) and CR (HR = 3.378, P = 0.014). HBsAg >200 IU/mL at the end of treatment (EOT) was associated with CR (HR = 3.573, P = 0.023) in patients developing VR. HBeAg-negative patients with low baseline viral loads and low HBsAg levels at EOT had minimal risk of CR after achieving APASL treatment endpoint (P = 0.016).The VR rate is high, but the risk of CR is low within 1 year with consolidation treatment after HBeAg seroconversion. Longer consolidation treatment to reduce the risk of VR should be considered in HBeAg-positive patients. As high risk of VR and CR, cessation of NUCs therapy could be considered only in selected HBeAg-negative patients.

CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study.

Background and Aims There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR. Methods Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment. Results Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 107 IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 107 IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%). Conclusions Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.

Changes of sex hormone levels in patients with hepatitis B virus-related postnecrotic cirrhosis: Relationship to the severity of portal hypertension

The effect of portal hypertension on plasma sex steroid levels was studied in 49 patients with hepatitis B virus-related postnecrotic cirrhosis. In accordance with the Child-Pugh classification, 18 patients were classified as grade A, 15 grade B and 16 grade C. At the same time, 25 males who were admitted for physical check-up served as normal controls. Serum testosterone levels decreased (3.31 +/- 2.03 vs. 5.65 +/- 0.13 ng/ml) and estrone levels increased (0.16 +/- 0.08 vs. 0.09 +/- 0.02 ng/ml) significantly in patients with cirrhosis compared to the levels obtained in the controls. Moreover, these changes were associated with an increased severity of cirrhosis (P < 0.05 when severity increased from grade A to C). Hemodynamic values regarding hepatic venous pressure gradient and cardiac output demonstrated significant differences in patients from grade A to C, but the correlation between these two parameters was poor (r = 0.3242). The hepatic venous pressure gradient, the only direct measurement of portal hypertension, did not correlate with any of the measured hormone levels in patients with cirrhosis. There was, however, a highly significant negative correlation between cardiac output and testosterone levels (r = -0.8754, P < 0.01) and a positive correlation between cardiac output and estrone levels (r = 0.7522, P < 0.05) in grade C patients. On the basis of these results, we concluded that gonadal dysfunction is a common finding in patients with hepatitis B related postnecrotic cirrhosis, especially in those with decompensated liver function. The relationship between cardiac output and severity of liver disease suggests that the degree of portosystemic shunting probably increases as liver disease worsens.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis.

Information on the efficacy of pegylated interferon (PEG-IFN) treatment of chronic hepatitis B (CHB) patients and predictors of the response based on real-world data is limited. Consecutive 201 patients who underwent PEG-IFN treatment for CHB were reviewed. A virological response (VR) was defined as a serum HBV DNA of <2000 IU/mL, and a combined response (CR) was defined a VR accompanied by serological response for hepatitis B e antigen (HBeAg)-positive CHB. For HBeAg-positive CHB patients, the HBeAg seroconversion rate and CR rate were 30.5% and 21.2% at 48 weeks after end of treatment (EOT), respectively. Baseline alanine aminotransferase (ALT) level was associated with HBeAg seroconversion, while baseline hepatitis B s antigen (HBsAg) levels of <250 IU/mL and HBV DNA <2.5 × 107 IU/mL were strongly associated with sustained off-treatment CR. For HBeAg-negative CHB, the VR rates were 85.5%, and 27.7% at EOT, and 48 weeks after EOT, respectively; a baseline HBsAg <1,250 IU/mL was associated with sustained off-treatment VR. PEG-IFN treatment has durable HBeAg seroconversion in HBeAg-positive CHB, but results in a high risk of relapse among HBeAg-negative CHB patients. Pre-treatment HBsAg level is an important predictor of VR in CHB patients undergoing PEG-IFN treatment.