Kevin Sh Liu

Patterns of hepatitis B surface antigen decline and HBV DNA suppression in Asian treatment-experienced chronic hepatitis B patients after three years of tenofovir treatment

BACKGROUND & AIMS Patterns of serum hepatitis B surface antigen (HBsAg) decline during nucleos(t)ide analogue (NA) therapy have not been well investigated. METHODS We determined the cumulative serologic, virologic, and biochemical outcomes of 142 Asian CHB patients, with at least 6 months exposure to other NAs, receiving tenofovir with or without lamivudine for up to 3 years. Liver biochemistry, serum HBV DNA, and HBsAg levels were determined at baseline, 6 months and yearly from years 1 to 3. RESULTS 142, 123 (86.6%), and 70 (49.3%) CHB patients were followed up for 1, 2, and 3 years, respectively. Two phases of HBsAg decline were observed. Patients with baseline HBsAg ≥3 log IU/ml, when compared to patients with baseline HBsAg < 3 log IU/ml, had a greater median rate of HBsAg reduction through 3 years of treatment (0.155 and 0.039 log IU/ml/year respectively, p < 0.001). Among patients with 3 years of follow-up, there was a significantly greater median rate of HBsAg reduction during the first year when compared to the second and third years (0.220, 0.136, and 0.081 log IU/ml/year respectively, p < 0.001). HBeAg status, HBV genotype, and concomitant lamivudine therapy were not important determinants of HBsAg kinetics (all p > 0.05). The 3-year cumulative virologic suppression rate was 93.3%, with no cases of resistance detected. CONCLUSIONS Serum HBsAg levels in NA-experienced patients receiving tenofovir demonstrated a variable pattern of decline, with slower rates of reduction noted in patients with lower baseline HBsAg levels, and could explain the rarity of HBsAg seroclearance during NA therapy.

Detection of Colorectal Adenoma by Narrow Band Imaging (HQ190) vs. High-Definition White Light Colonoscopy: A Randomized Controlled Trial

OBJECTIVES:The benefits of narrow band imaging (NBI) on enhancing colorectal adenoma detection remain questionable. We tested whether the new generation of NBI (190-NBI), which is twice as bright as the previous version, would improve adenoma detection when compared with high-definition white light (HD-WL) colonoscopy.METHODS:It was a randomized controlled trial with tandem colonoscopy. We recruited patients who underwent colonoscopy for symptoms, screening, or surveillance. Patients were randomized for the use of either 190-NBI or HD-WL on withdrawal. Tandem colonoscopy was performed by using the same assigned colonoscope and withdrawal method. Lesions detected on first-pass and second-pass examination were used for adenoma detection and miss rates, respectively. The primary outcomes were adenoma and polyp detection rates.RESULTS:A total of 360 patients were randomized to undergo either 190-NBI or HD-WL colonoscopy. Both the adenoma and polyp detection rates were significantly higher in the 190-NBI group compared with the HD-WL group (adenoma: 48.3% vs. 34.4%, P=0.01; polyps: 61.1% vs. 48.3%, P=0.02). The mean number of polyps detected per patient was higher in the 190-NBI group (1.49% vs. 1.13, P=0.07). There was no significant difference in the adenoma miss rates between the two groups (21.8% vs. 21.2%). Multivariate analysis showed that the use of 190-NBI (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.10–3.12), withdrawal time (OR 1.29; CI 1.19–1.38), patients age (OR 1.04; CI 1.01–1.06), and male gender (OR 2.38; CI 1.42–3.99) were associated with adenoma detection.CONCLUSIONS:190-NBI colonoscopy was superior to the conventional HD-WL in detecting colorectal adenomas or polyps, but there was no significant difference in adenoma miss rates.

Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and secondline treatment for Helicobacter pylori in Chinese patients: an open label, randomised, crossover trial

Objective Treatments with sequential therapy (SEQ) or bismuth quadruple (QUAD) therapy have been proposed as empirical firstline regimens for Helicobacter pylori. We compared the efficacy and tolerability of 10 day SEQ with 10 day modified QUAD as both firstline and secondline treatments for H pylori in a randomised crossover study. Design H pylori positive and treatment naïve patients were randomly assigned to receive either 10 day SEQ (esomeprazole for 10 days, amoxicillin for an initial 5 days, followed by clarithromycin and metronidazole for a subsequent 5 days) or modified QUAD (esomeprazole, bismuth subcitrate, tetracycline and metronidazole). H pylori eradication was confirmed by urea breath test at 8 weeks. Patients who failed the initial assigned treatment were crossed over to receive the alternate regimen. The primary outcome was eradication rates of firstline treatment by intention to treat (ITT) and per protocol (PP) analyses. Results 357 patients were randomised to receive either SEQ or QUAD. The PP eradication rates of the SEQ and QUAD groups were 95.2% and 98.8%, respectively (p=0.10). Based on ITT analysis, the corresponding eradication rates were 89.4% and 92.7%, respectively (p=0.36). Eight (4.8%) patients in the SEQ and two (1.2%) patients in the QUAD who failed the firstline treatment were crossed over to the alternate regimen with 100% retreatment success. The overall incidence of adverse events was higher in the QUAD (16.7%) than in the SEQ (8.1%; p=0.032) group. Conclusions Ten day sequential and modified bismuth quadruple therapies are both highly effective as empirical firstline therapies for H pylori in Chinese patients. ClinicalTrials.gov NCT 01760824

Outcome of lamivudine-resistant chronic hepatitis B after up to 5 years of combination therapy with adefovir.

BACKGROUND There is a paucity of data on the long-term efficacy of combination lamivudine and adefovir therapy in patients with lamivudine-resistant chronic hepatitis B. METHODS We determined the cumulative virological, serological and biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir for up to 5 years. Resistance profiles using a line probe assay were determined among patients with detectable viraemia. The significance of different baseline and on-treatment virological parameters was analysed. RESULTS The median age and duration of follow-up were 45.1 years and 37.1 months, respectively. The cumulative rates of HBV DNA undetectability (<20 IU/ml), alanine aminotransferase normalization and hepatitis B e antigen seroconversion up to 5 years were 74.0%, 95.1% and 44.4%, respectively. One patient achieved hepatitis B surface antigen seroclearance. The 5-year cumulative resistance rate to adefovir was 10.2%. Among different baseline and on-treatment virological parameters, week 24 HBV DNA<200 IU/ml was associated with an increased chance of long-term virological suppression (P<0.001, OR 13.89, 95% CI 3.90, 49.46). Primary non-response and high baseline viral titres were not useful in predicting long-term virological outcomes. The 5-year cumulative rate of serum creatinine elevation >0.5 mg/dl was 4.1%. CONCLUSIONS Combination lamivudine and adefovir therapy for up to 5 years achieved modest rates of virological suppression, but resistance developed in only 10.2% of patients. Week 24 HBV DNA<200 IU/ml was predictive of favourable long-term virological outcomes and could be used to assist treatment decisions on continuing lamivudine and adefovir or switching to more potent therapy.

The Effects of IL-28B and ITPA Polymorphisms on Treatment of Hepatitis C Virus Genotype 6

To the editor: We read with interest a review article by Clark et al. (1). Two single-nucleotide polymorphisms (SNPs; rs12979860 and rs8099917) around the interleukin (IL)-28B gene locus were found by genome-wide association studies (GWAS) to be independent predictors of treatment response for hepatitis C virus (HCV) genotype 1. Other SNPs of interest identified by GWAS in HCV are the inosine triphosphatase (ITPA) gene polymorphisms (one of which is rs1127354). It is associated with protection from ribavirin-induced hemolytic anemia in genotype 1 patients (2).

Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial

Background Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin‐naproxen‐oseltamivir combination for treatment of serious influenza. Methods From February to April 2015, we conducted a prospective open‐label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2‐day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30‐day mortality. The secondary end points were 90‐day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase‐inhibitor‐resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. Results Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30‐day follow‐up. The combination treatment was associated with lower 30‐day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1‐3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1‐2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30‐day mortality (OR, 0.06; 95% CI, 0.004‐0.94; P = .04). Conclusions Combination treatment reduced both 30‐ and 90‐day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. Trial Registry BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879

Longitudinal profiles of highly sensitive hepatitis B surface antigen levels: re-evaluation of HBsAg seroclearance

Serologic profiles after hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) have not been well‐studied.

Factors for hepatitis B vaccination and abnormal liver function in Chinese patients with inflammatory bowel disease: A single center experience

We aimed to determine the prevalence of chronic and past hepatitis B virus (HBV) infection in Chinese patients with inflammatory bowel disease (IBD), and to determine the risk factors associated with having received no vaccination for HBV and abnormal liver function among our patients.

Inverse relationship between hepatic steatosis and hepatitis B viremia: Results of a large case‐control study

The potential interaction between chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD), two of the most prevalent liver diseases worldwide, has not been well defined. We performed liver stiffness (LS) and controlled attenuation parameter (CAP) measurements using transient elastography in 1202 CHB patients. Of these, 601 steatotic patients were matched with nonsteatotic controls in a 1:1 ratio by age, gender, nucleoside analogue treatment status, and treatment duration. Severe fibrosis was defined according to EASL‐ALEH criteria, and steatosis was defined as CAP ≥222 dB m−1. Anthropometric measurements and metabolic‐related parameters were recorded. The mean age of the 1202 patients (51.4% male) was 51.8 years. 696 patients (57.9%) were on nucleoside analogues for a median duration of 76.2 months. Among treatment‐naïve patients, median serum HBV DNA was lower in steatotic individuals than in controls (3.0 vs 3.4 log IU mL−1, P < .05), with this inverse relationship remaining significant in multivariate analysis (odds ratio 0.859, 95% CI 0.743‐0.994, P < .05). With increased steatosis severity, there was a stepwise decrease in median HBV DNA levels (3.1 and 2.6 log IU mL−1 in no steatosis and severe steatosis, respectively, P = .032). Steatosis was associated with a higher median LS (5.4 kPa vs 5.0 kPa, P < .001). Severe steatosis, when compared to mild/moderate steatosis, was associated with an increased percentage of severe fibrosis (23.2% and 12.6%, respectively, P = .005). We conclude that severe steatosis was associated with increased fibrosis in CHB patients. Increasing steatosis was independently associated with lower serum HBV DNA levels, suggesting its potential negative effects on viral replication.

Association Between Hepatic Steatosis, Measured by Controlled Attenuation Parameter, and Fibrosis Burden in Chronic Hepatitis B

Background & Aims The interaction between chronic hepatitis B (CHB) and hepatic steatosis is poorly understood. We investigated whether measurement of controlled attenuation parameter (CAP), a non‐invasive method to quantify steatosis, can assist in monitoring patients with CHB. Methods We performed transient elastography, to measure liver stiffness, and made CAP measurements in 1606 patients with CHB (898 treated with nucleoside analogues, for a median 75.4 months) in Hong Kong, from January 2015 through September 2016. We also collected information on patients’ medical history, current treatment, and smoking and alcohol habits, anthropometric measurements. We obtained and analyzed fasting blood samples. Severe liver fibrosis was defined, according to guidelines, as a liver stiffness measurement greater than 9.0 kPa in patients with normal level of alanine aminotransferase (ALT) or greater than 12.0 kPa in patients with a level of ALT 1–5‐fold the upper limit of normal. Steatosis was defined as a CAP measurement of 248 dB/m or more, and severe steatosis as a CAP measurement or 280 dB/m more. We performed multivariate analysis to identify factors associated with severe fibrosis. Results The prevalence of steatosis, severe steatosis, and severe fibrosis in our cohort were 40.8%, 22.6%, and 14.1%, respectively. A higher proportion of patients with severe steatosis had severe fibrosis (21.4% vs 11.9% in the overall cohort; P < .001). In multivariate analysis, severe steatosis was associated with severe fibrosis in treatment‐naïve patients (odds ratio, 3.60, 95% CI, 1.21–10.75) and in patients receiving treatment (odds ratios: 1.95 [1.06‐3.61] for 3 or more years of treatment, 2.28 [1.13‐4.61] for 5 or more years of treatment, and 2.79 [1.17‐6.62] for 7 or more years of treatment). With every increase in CAP value of 10 dB/m, the risk of severe fibrosis increased by 15% in treatment‐naïve patients and by 7%–8% in patients receiving treatment. Conclusions Severe steatosis, determined by CAP measurement, is associated with severe fibrosis in treatment‐naïve patients with CHB and in patients receiving treatment. Longitudinal studies are required to investigate if steatosis control, in addition to antiviral treatment, can reduce the burden fibrosis in patients with CHB.