Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population.

BACKGROUND AND AIMS: The aim of the present study was to determine the population prevalence of occult hepatitis B (OHB) infection and its clinical profile in a highly endemic area of chronic hepatitis B virus disease. METHODS: OHB was first identified by individual sample testing for hepatitis B surface antigen (HBsAg) followed by nucleic acid testing (NAT) and vice versa for 3044 (cohort 1, stored sera from donation within 1 year) and 9990 (cohort 2, prospective study) blood donors, respectively. OHB was confirmed meticulously by ≥2 out of 3 tests with detectable hepatitis B virus (HBV) DNA using a sensitive standardised assay. Detailed serology and viral load in the serum and liver were studied. RESULTS: The prevalence of OHB was 0.13% (4/3044) and 0.11% (11/9967) for cohort 1 and 2, respectively. In cohort 2, 10 out of 11 OHB samples were positive for anti-HBc (hepatitis B core antigen) antibody (all were immunoglobulin G). Seven had detectable anti-HBs. The serum HBV DNA levels were extremely low (highest 14.1 IU/ml). Of the six donors who underwent liver biopsies, all had normal liver biochemistry, extremely low liver HBV DNA (highest 6.21 copies/cell) and nearly normal liver histology. For those with viral sequence generation, none had the common HBsAg mutant G145R. CONCLUSIONS: The prevalence of OHB in a highly endemic area of chronic HBV was very low, thus implying a low impact on transfusion services. To implement universal screening, the high cost of NAT should be taken into account. OHB blood donors had very low HBV replication, and normal liver biochemistry and histology, conferring a favourable prognosis.

Clarithromycin-amoxycillin-containing triple therapy: a valid empirical first-line treatment for Helicobacter pylori eradication in Hong Kong?

BACKGROUND: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin-clarithromycin-containing triple therapy as first-line treatment have fallen below 80%. Levofloxacin-containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7-day clarithromycin-containing triple therapy against the 7-day levofloxacin-containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first-line treatment for H. pylori infection in Hong Kong. METHODS: Three hundred consecutive H. pylori-positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by (13)C-urea breath test 6 weeks after treatment. Patients who failed either of the first-line eradication therapy were invited to undergo H. pylori susceptibility testing. RESULTS: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention-to-treat and per-protocol analysis. More patients in the clarithromycin- than the levofloxacin-containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 microg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 microg/mL). CONCLUSIONS: The standard 7-day clarithromycin-containing triple therapy is still valid as the most effective empirical first-line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first-line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.

Quality of life in patients with laryngopharyngeal reflux.

BACKGROUND: Laryngopharyngeal reflux (LPR) disease is an extraesophageal manifestation of gastroesophageal reflux disease (GERD). The impact of GERD-related LPR on the psychological well-being and quality of life (QOL) in Chinese is not known. AIM: To assess the QOL in patients with LPR disease. METHODS: 76 LPR and 73 healthy subjects were recruited. Psychological well-being was assessed by the Hospital Anxiety and Depression Score and QOL was assessed by SF-36. RESULTS: 51/76 (67.1%) patients had GERD-related LPR. More LPR subjects had taken sick leave (36.2 vs. 5.6%, p = 0.001) and reported adverse social life impact (60.5 vs. 38.9%, p = 0.013). LPR patients showed significantly worse results on the Voice Handicap Index (47.8 vs. 7.6, p = 0.001), were more anxious and had worse QOL in social functioning, pain and general health perception domains of SF-36. GERD-related LPR subjects had a higher depression score (4.8 vs. 3.8, p = 0.014) and a lower mental summary score (41.8 vs. 48.4, p = 0.01) in SF-36 compared with those without GERD. CONCLUSIONS: LPR had a negative impact on psychological status, social functioning and QOL. GERD symptoms appeared to be the main contributor to decrease QOL. GERD-related LPR patients had a significant impact on the mental component of their QOL.

Gastroesophageal reflux disease is associated with poor asthma control, quality of life, and psychological status in Chinese asthma patients.

BACKGROUND: Both asthma and gastroesophageal reflux disease (GERD) are common, often coexist, and have significant impact on a patient's quality of life. Our aim was to determine the prevalence of GERD in asthmatic patients at a major hospital in Hong Kong, and to examine the impact of GERD and its association with asthma control. METHODS: Patients with asthma who attended the respiratory clinic at Queen Mary Hospital, Hong Kong, were recruited. Demographic data were collected, and a validated Chinese GERD questionnaire was used. The Medical Outcomes Study 36-item short form (SF-36) was used to assess quality of life, and the Hospital Anxiety and Depression Scale (HADS) was used to assess psychological status. Asthma control was assessed by the asthma control test. RESULTS: A total of 218 patients were recruited; 40.4% of asthmatic patients (88 patients) had GERD, as defined by the GERD questionnaire. Compared with those patients without GERD, those with GERD had significantly worse asthma control (p = 0.022), worse quality of life in all domains of the SF-36 (all p < 0.01), and more anxiety (6.82 vs 4.90, respectively; p < 0.001) and depression (6.09 vs 4.05, respectively; p < 0.001) as reflected by HADSs. CONCLUSIONS: A significant proportion of asthmatic patients in Hong Kong have GERD, and this is associated with poorer asthmatic control, quality of life, and psychological status.

Quality of life and psychological impact in patients with noncardiac chest pain.

BACKGROUND: Chest pain is common and data regarding noncardiac chest pain (NCCP) in Asia are lacking. AIM: To determine the differences in clinical presentations, psychologic impact, and quality of life between patients with NCCP and cardiac chest pain (CCP), and to identify any factors that impacted on these patients. METHODS: Consecutive patients undergoing coronary angiography for the evaluation of chest pain were recruited in Hong Kong and Wuhan, China. One hundred and forty patients with abnormal and 141 patients with normal angiography were included in the study. The validated gastroesophageal reflux disease questionnaire, the Hospital Anxiety-Depression Scale, and the 12-item Short Form Health Survey (SF-12) were used for assessment. RESULTS: NCCP patients reported similar days-off work and impairment of their social life compared with those with CCP. No difference was found in the anxiety and depression scores between the 2 groups. NCCP patients with reflux symptoms had higher anxiety score (7.19 vs. 5.74, P=0.044), reported more interruption of their social life (26% vs. 5%, P<0.0001), and had taken more sick leaves (17% vs. 5%, P=0.018) compared with those without gastroesophageal reflux disease. CONCLUSIONS: The quality of life and psychologic impact of patients with NCCP were as significant as those with CCP. NCCP patients with reflux symptoms were more anxious and were impaired in their productivity and social life.

Factors affecting physicians' practices related to Helicobacter pylori infection: effect of experience and mode of practice.

BACKGROUND: Studies found that guidelines on the management of Helicobacter pylori were not always followed in clinical practice. This study investigated factors that were responsible for the deviation. METHODS: A cross-sectional survey using a structured self-administered questionnaire was used to ask physicians whether they would offer testing and treatment for H. pylori infection in different clinical scenarios. RESULTS: 170 medical practitioners completed the questionnaires. Respondents in the private sector were significantly more likely to test and treat than those in the public sector for patients with a history of peptic ulcer, gastric cancer or no symptom (p = 0.018, <0.001 and 0.041, respectively). Significant differences in practice were noted amongst practitioners of different specialty and seniority, but not qualification. Medical practitioners in the private sector complied with the guidelines significantly better than those in the public sector (p = 0.002) and so did senior practitioners compared with junior practitioners (p < 0.001). The specialty and qualification of the respondents, however, did not have a significant effect. CONCLUSION: There were significant differences in the management of H. pylori amongst medical practitioners from the private and public sectors and amongst senior and junior practitioners. Published guidelines were not completely followed. Further educational campaigns are needed.

Management and outcome of peptic ulcers or erosions in patients receiving a combination of aspirin plus clopidogrel.

BACKGROUND: This multicenter retrospective study investigated the management and outcome of patients with peptic ulcer/erosion-related aspirin and clopidogrel (A + C) cotherapy. METHODS: From January 2002 to September 2006, patients with endoscopically proven peptic ulcers/erosions after receiving A + C cotherapy were analyzed. RESULTS: This group consisted of 106 patients (age, 69.3 +/- 11.7 years). Ulcers/erosions developed in 27 patients during hospitalization for cardiac events and in 79 patients after hospital discharge. Of 27 patients hospitalized for acute cardiac events, gastrointestinal (GI) bleeding and dyspepsia occurred in 24 and three, respectively. The most common lesion was gastric ulcer. Of 79 discharged patients, GI bleeding and dyspepsia occurred in 64 and 15, respectively. The most common bleeding and dyspeptic lesions were gastric ulcer and gastritis, respectively. Overall, 17 patients underwent endoscopic hemostasis all successfully. A + C cotherapy was continued in 57 patients for a median (interquartile range) of 3.0 (6.2) months. Most were coprescribed a proton pump inhibitor (PPI) (53, 93%). No recurrent GI bleeding was observed. CONCLUSIONS: After A + C cotherapy, gastric ulcer or gastritis were the most common endoscopic lesions. The combination of a PPI and endoscopic treatment for ulcer bleeding was highly successful. After patient stabilization, continuation of A + C cotherapy with a PPI appears to be safe.

Prevalence of fibrosis and cirrhosis in chronic hepatitis B: implications for treatment and management.

OBJECTIVE: To document the prevalence and factors associated with severe fibrosis and cirrhosis in a large population of Asian chronic hepatitis B (CHB) patients. METHODS: Transient elastography was performed in unselected CHB patients. Liver stiffness score of <8.1 kPa was used as a cut-off for the presence of severe fibrosis or liver cirrhosis. RESULTS: 1315 patients were recruited, of which 951 (72%) were treatment-naive. Of these, 319 (34%) had severe fibrosis, with higher prevalence seen in males compared with females (39% vs 24% respectively, p < 0.01. Severe fibrosis was seen with increasing age from 20% in patients <25 years to 81% in those >65 years. Higher prevalence of severe fibrosis was seen in HBeAg(+) patients compared to HBeAg(-) patients age >45 years (58% vs 43% respectively, p = 0.03), in patients with HBV DNA levels >or=4 log compared with <4 log copies/ml (41% vs 27% respectively, p < 0.01), and in patients with stepwise increase of ALT levels (<0.5 x ULN vs 0.5-1 x ULN vs 1-2 x ULN; 11% vs 30% vs 48% respectively, p < 0.01). After multivariate analysis, gender, age and ALT levels were significant factors associated with severe fibrosis. Patients who received antiviral treatment had lower ALT, stiffness score and prevalence of cirrhosis compared to treatment-naive patients [25 vs 35 U/L (p < 0.01), 6.2 vs 6.7 kPa (p = 0.031) and 14% vs 22% (p = 0.008) respectively]. CONCLUSION: The overall prevalence of severe fibrosis in CHB patients was 34% with higher rates seen in older age groups, males, and in patients with higher ALT levels.

Treatment of Helicobacter pylori and prevention of gastric cancer.

Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue.

Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.

XIAP-associated factor 1 (XAF1) is a novel tumor suppressor and interferon stimulated gene (ISG). Interferon beta (IFNbeta) exerts anti-proliferative effect and induces apoptosis through the Jak-Stat signaling cascade by the type I Interferon receptor (IFN-R), which initiates gene transcription of those biological effectors of IFNbeta. The aim of this study is to determine the effect of IFNbeta on XAF1 expression and the putative mechanisms mediated by the critical role of signal transducers and activators of transcription 1 (Stat1). Gene expression was detected by RT-PCR and Western blot analysis. The promoter activity of XAF1 was examined by luciferase reporter assay. The activity of interferon stimulated response element (ISRE) was assessed by electrophoretic mobility shift assay (EMSA) and quantitative chromatin immunoprecipitation assay (Q-ChIP). Results showed that IFNbeta stimulated XAF1 promoter activity in colon cancer cell line DLD1 in a time- and dose-dependent manner. A high affinity ISRE binding element (ISRE-XAF1) was located in -55 to -66 nt upstream of the first ATG site of XAF1 gene. Deletion of ISRE-XAF1 completely abrogated basal and IFNbeta-induced promoter activity. IFNbeta-induced XAF1 expression was mediated by Stat1 through the interaction with ISRE-XAF1. Knocking down of the Stat1 expression and blocking its phosphorylation decreased IFNbeta-induced XAF1 expression. Results suggested that induction of an immediate early response gene-XAF1 by IFNbeta was mediated by the transcription regulator Stat1 through the ISRE site within the promoter region of XAF1 gene in colon cancer.

Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease.

CONTEXT: Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. OBJECTIVES: To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. DESIGN, SETTING, AND PARTICIPANTS: Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. MAIN OUTCOME MEASURES: The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. RESULTS: The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by chi2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD. CONCLUSIONS: In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.

Symptom resolution does not predict healing of erosive oesophagitis in Chinese.

BACKGROUND: Previous studies suggested that Chinese have a milder spectrum of gastro-oesophageal reflux disease and a lower dose of proton pump inhibitors (PPI) is sufficient for the control of symptoms as compared with the Western population. AIMS: To determine if 8 weeks of esomeprazole 20 mg daily would be adequate for both symptom resolution and oesophagitis healing in Chinese patients and the predictive factors for the response. METHODS: 66 patients with oesophagitis were included. Oesophagitis severity was graded by Los Angeles (LA) classification. 61 patients underwent 24-hour ambulatory pH study at baseline. All were given esomeprazole 20 mg daily for 8 weeks. Symptom response and healing of oesophagitis was assessed at the end of the treatment period. RESULTS: 75.8% of the patients had complete reflux symptom resolution but only 48% had complete healing of the oesophagitis at endoscopy after 8 weeks of treatment. LA classification grading at baseline endoscopy (p < 0.0001) and total number acid reflux episodes on 24-hour pH monitoring prior to treatment (p = 0.007) were both good predictors of oesophagitis healing but not for symptom resolution. CONCLUSIONS: Our results suggested that 8 weeks of lower dose PPI is not sufficient for oesophagitis healing. Symptom resolution with PPI does not predict oesophagitis healing in Chinese.

Noncardiac chest pain--an Asia-Pacific survey on the views of primary care physicians.

Noncardiac chest pain (NCCP) is common and has a significant impact on health care. Primary care physicians (PCPs)' attitudes, clinical approach, preference of diagnostic tests, referral patterns, and comfort in managing patients with NCCP in the Asia-Pacific region are not known. Consequently, we performed this survey in the Asia-Pacific region. The self-completed questionnaire was sent to PCPs in the Asia-Pacific region. A 28-item questionnaire contained questions on demographic information, characteristics of practice, preferences of diagnostic tests, referral patterns, treatment plans, and opinion on Helicobacter pylori and NCCP. A total of 108 (74%) PCPs returned the questionnaire. A mean of 18% of the patients were diagnosed with NCCP by PCPs in the past 6 months. Ninety-four percent of PCPs had treated NCCP patients in the last 6 months. Only 38% of the PCPs were comfortable in diagnosing NCCP but 85.2% believed that they should manage NCCP patients. PCPs in Malaysia and Philippines were more likely to refer patients to subspecialists. Fifty-seven and four-tenths percent of PCPs believed that H. pylori infection plays a role in the development of NCCP. The study demonstrates clearly that the understanding, diagnostic strategies, and treatment strategies of NCCP in the Asia-Pacific region are suboptimal and thus highlights the importance of educational and training programs tailored for PCPs in NCCP.

Helicobacter pylori eradication for gastric cancer prevention.

Gastric cancer is the second most common fatal malignancy in the world. Its incidence is high in East Asia. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have established a strong causal relationship between H. pylori infection and gastric cancer. H. pylori eradication is therefore likely to be one of the most promising approaches to gastric cancer prevention. Animal studies have shown that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. However, the available data from human studies show that H. pylori eradication does not completely prevent gastric cancer and that it might be useful only in patients without atrophic gastritis or intestinal metaplasia at baseline. Longer follow-up and additional studies are needed to clarify this issue.

Gastroesophageal reflux disease in Asian countries: disorder of nature or nurture?

Gastroesophageal reflux disease (GERD) is less prevalent in Asia than in the West, but there is now evidence to suggest that its frequency is rapidly rising in Asia. The different prevalence rates reported in various Asian studies may represent different points in the 'rising' phase of GERD. The cause for the lower but increasing prevalence of GERD in Asia is not known, but genetics and to some extent environmental factors, may have initially protected Asians against GERD. However, with the recent globalization of economies, the associated lifestyle changes in many developing Asian countries may have tipped the balance in favor of the development of GERD.

Hepcidin is down-regulated in alcoholic liver injury: implications for the pathogenesis of alcoholic liver disease.

BACKGROUND: Alcoholic liver disease is known to be associated with abnormal iron homeostasis, and iron metabolism itself is regulated by the liver-derived peptide hepcidin. Both CCAAT enhancer binding protein alpha (C/EBPalpha) and interleukin 6 (IL-6) have been shown to regulate hepcidin gene transcription. AIM: To investigate mechanisms underlying alcohol-induced disturbances in iron homeostasis by measuring the expression of hepcidin and C/EBPalpha mRNA using in vivo and in vitro models of alcoholic liver injury. METHODS: Male rats were pair-fed an alcoholic liquid diet for 12 weeks. RT-PCR was performed on liver tissue using specific primers for hepcidin and C/EBPalpha. The effect of alcohol on hepcidin and C/EBPalpha gene expression was also determined in isolated hepatocytes, HuH-7 cells and HepG2 cells treated with 50 mM ethanol, 200 microM acetaldehyde, and/or 20 ng/ml IL-6. RESULTS: Hepcidin and C/EBPalpha mRNA expression were significantly decreased in alcohol-fed rats compared with pair-fed controls (6-fold p < 0.001 and 2.2-fold p < 0.0002 reduction, respectively) and hepatic lipid peroxidation was increased by 32.5% (p < 0.05) in alcohol-fed rats compared with controls. Hepcidin gene expression was not altered significantly in cells cultured in the presence of 50 mM ethanol. Following 24 hour stimulation by IL-6, there was a 4-fold increase in hepcidin expression in hepatocytes and a 9-fold increase in HuH-7 cells. Ethanol (50 mM) attenuated the IL-6-induced increase in hepcidin expression in HuH-7 cells (9-fold to a 4-fold increase) but not in hepatocytes. Acetaldehyde had no effect on hepcidin gene expression in cells in culture. CONCLUSION: The down-regulation of hepcidin and C/EBPalpha gene expression shown in vivo implies disturbed iron sensing contributing to the hepatosiderosis seen in alcoholic liver disease, possibly by mechanisms involving the IL-6 signaling cascade.

Hepatic hydropericardium.

A 41-year-old man with chronic hepatitis C and cirrhosis presented with pericardial effusion and tamponade requiring pericardiocentesis. Nine liters of pericardial fluid was drained with complete resolution of his ascites. He represented with recurrent pericardial effusions despite salt restriction and diuretic therapy. Subsequent radionuclide scans demonstrated a direct connection between the peritoneal and pericardial spaces. A pericardial window was formed but despite this there was recurrence of pericardial effusion and pleural effusion. The patient underwent orthotopic liver transplantation 7 months later and no recurrence of pleural or pericardial effusion was observed following transplantation. We believe this is the first case report of pericardial effusion secondary to cirrhotic ascites and a communication between the peritoneal and pericardial cavities.