Questionnaire survey on knowledge, attitudes, and behaviour towards viral hepatitis among the Hong Kong public.

INTRODUCTION: We aimed to identify gaps in knowledge, attitudes, and behaviours towards viral hepatitis among the Hong Kong public and provide insights to optimise local efforts towards achieving the World Health Organization's viral hepatitis elimination target. METHODS: A descriptive, cross-sectional, self-reported web-based questionnaire was administered to 500 individuals (aged ≥18 years) in Hong Kong. Questionnaire items explored the awareness and perceptions of viral hepatitis-related liver disease(s) and associated risk factors in English or traditional Chinese. RESULTS: The majority (>80%) were aware that chronic hepatitis B and/or C could increase the risks of developing liver cirrhosis, cancer, and/or failure. Only 55.8% had attended health screenings in the past 2 years, and 67.6% were unaware of their family's history of liver diseases. Misperceptions surrounding the knowledge and transmission risks of viral hepatitis strongly hint at the presence of social stigmatisation within the community. Many misperceived viral hepatitis as airborne or hereditary, and social behaviours (casual contact or dining with an infected person) as a transmission route. Furthermore, 62.4% were aware of hepatitis B vaccination, whereas 19.0% knew that hepatitis C cannot be prevented by vaccination. About 70% of respondents who were aware of mother-to-child transmission were willing to seek medical consultation in the event of pregnancy. Gaps in knowledge as well as the likelihood of seeking screening were observed across all age-groups and education levels. CONCLUSIONS: Comprehensive hepatitis education strategies should be developed to address gaps in knowledge among the Hong Kong public towards viral hepatitis, especially misperceptions relevant to social stigmatisation and the importance of preventive measures, including vaccination and screening, when exposed to risk factors.

Ethnic influence on nonalcoholic fatty liver disease prevalence and lack of disease awareness in the United States, 2011-2016.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a rising global disease associated with clinical and economic burdens. OBJECTIVES: We aimed to quantify NAFLD prevalence and awareness to provide stakeholders necessary information to combat NAFLD burden. METHODS: This study utilizes data from the National Health and Nutrition Examination Survey 2011-2016 and included 4538 adult participants who did not have heavy drinking or viral hepatitis history. The US fatty liver index defined NAFLD and NAFLD fibrosis score defined fibrosis. NAFLD awareness was captured by questionnaire. RESULTS: Amongst the study population of 4538 persons, NAFLD prevalence was 32.5%, lowest in non-Hispanic Blacks (18.0%) and Asians (18.1%), highest amongst Mexican Americans (48.4%). Within the NAFLD group, advanced fibrosis was highest in non-Hispanic Blacks (28.5%) and lowest amongst non-Hispanic Asians (2.7%). Of the 1473 (97.5%) NAFLD participants who answered NAFLD awareness question, 90% visited a healthcare centre at least once in the past year, but only 5.1% were aware of having NAFLD. On weighted population estimates, 77.33 million persons had NAFLD, 17.63 million had advanced fibrosis, and 73.39 million NAFLD participants were not aware of having NAFLD. CONCLUSIONS: Of 77.33 million people in the United States have NAFLD with 17.63 million having advanced fibrosis, with lowest prevalence in non-Hispanic Asians and highest in Mexican Americans. A conundrum exists amongst non-Hispanic Blacks who have low NAFLD prevalence but highest prevalence of advanced fibrosis. Awareness of NAFLD was low across all ethnicities. Effort is needed to improve disease awareness whilst addressing NAFLD clinical burden across ethnicities.

Carbohydrate knowledge, lifestyle and insulin: an observational study of their association with glycaemic control in adults with type 1 diabetes.

BACKGROUND: The ability to achieve optimal glycaemic control varies widely among individuals with type 1 diabetes. The present study aimed to explore the factors that are associated with optimal glycaemic control compared to suboptimal control. METHODS: An observational study design was used to explore the association of various factors with glycaemic control. Surveys were completed by individuals who attended the type 1 diabetes clinic at a tertiary hospital in New South Wales (NSW), Australia. Clinical and demographic information and attendance at dietary review were also collected. RESULTS: One hundred and three individuals completed the survey. Those with optimal control [glycated haemoglobin ≤7.0% (53 mmol mol-1 )] had a significantly shorter mean (SD) duration of diabetes [10.1 (12.6) years versus 18.8 (12.8) years, P = 0.005), were less likely to omit basal and bolus insulin (18.2% versus 47.5%, P = 0.016; 36.4% versus 61.8%, P = 0.034, respectively), and were less likely to report low confidence in managing their diabetes (9.1% versus 35.4%, P = 0.017). Participants who were able to identify carbohydrate sources were significantly more likely to have attended dietary review in the past 12 months (60.5% versus 20.0%, P = 0.001). However, they were not more likely to have better glycaemic control. CONCLUSIONS: The present study identified that consistency in taking insulin and confidence in self-management was associated with better glycaemic control. An association was also found between recent dietary review and better carbohydrate knowledge, although this did not translate into better glycaemic control. Future investigation into the application of carbohydrate knowledge is required.

Introduction of New South Wales adult subcutaneous insulin-prescribing chart in a tertiary hospital: its impact on inpatient glycaemic control.

BACKGROUND: Erratic blood glucose levels (BGL) are commonly observed amongst patients with diabetes mellitus during hospital admission. Patients on insulin therapy often do not have their doses titrated adequately by their team doctors during admission, and insulin is well known to be a high-risk medication prone to administration error. AIM: To assess the impact of a state-wide adult subcutaneous insulin-prescribing chart (ASCIPC) on glycaemic control and insulin-prescribing pattern in a tertiary hospital. METHODS: An audit on the clinical records of inpatients who were on subcutaneous insulin therapy in the first week of July 2014 (prior to ASCIPC, n = 56) and in the first week of July 2015 (10 months after introducing ASCIPC, n = 62) was conducted at Liverpool Hospital. RESULTS: Following the introduction of ASCIPC, fewer BGL readings were missed (9.1 vs 11.6%, P = 0.032), and medical officers were more likely to adjust insulin dosage (71.0 vs 42.6%, P = 0.002) when compared to baseline. Glycaemic control improved, with lower mean BGL (9.4 ± 2.0 vs 10.4 ± 2.6 mmol/L, P = 0.021) and a greater proportion of BGL within the normal range of 5-10 mmol/L (56.2 vs 47.7%, P = 0.041). Omission of insulin doses after ASCIPC remained common, with over 40% of patients having at least one dose of insulin omitted during the audit week. CONCLUSION: Our study showed that the introduction of ASCIPC had positive impacts on glycaemic management for patients on subcutaneous insulin therapy during admission. More work is required to reduce the rate of insulin omission and to improve further glycaemic control for inpatients.

The rtA181S mutation of hepatitis B virus primarily confers resistance to adefovir dipivoxil.

The study aimed to clarify clinical significance of hepatitis B virus (HBV) rtA181S mutation in Chinese HBV-infected patients. A total of 18 419 patients with chronic HBV infection from Beijing 302 Hospital were investigated. HBV complete reverse transcriptase region of polymerase was screened by direct sequencing, and the results were verified by clonal sequencing. Replication-competent mutant and wild-type HBV genomic amplicons were constructed and transfected into the HepG2 cells and cultured in the presence or absence of serially diluted nucleos(t)ide analogues. Intracellular HBV replicative intermediates were quantitated for calculating the 50% effective concentration of the drug (EC(50)). The rtA181S was detected in 98 patients with 12 kinds of mutational patterns. Genotype C and genotype B HBV infection occupied 91.8% and 8.2% in rtA181S-positive patients, in contrast to 84.6% and 15.4% in rtA181S-negative patients (P < 0.01). All rtA181S-positive patients had received nucleos(t)ide analogues. rtA181S was detected in multiple patients with virologic breakthrough. Phenotypic analysis of patient-derived viral strains showed that rtA181S, rtA181S+N236T, rtN236T and rtA181V strains had 68.5%, 49.9%, 71.4% and 66.2% of natural replication capacity of wild-type strain, and 3.7-fold, 9.8-fold, 7.9-fold and 5.6-fold increased EC(50) to adefovir dipivoxil (ADV). The rtA181S strain remained susceptible to lamivudine, entecavir and tenofovir, and ADV susceptibility was restored after the mutation was eliminated through site-directed mutagenesis. Rescue therapy with entecavir or combination therapy was effective in rtA181S-related ADV-refractory patients. The rtA181S mutation confers moderate resistance to ADV. It could be induced by either lamivudine or ADV and contribute ADV treatment failure.

Combination therapy of interferon and nucleotide/nucleoside analogues for chronic hepatitis B.

Chronic hepatitis B is one of the leading causes of cirrhosis and hepatocellular carcinoma globally. At present, seven drugs, including two interferons and five oral nucleos(t)ide analogues (NAs), have been approved for the treatment of chronic hepatitis B. Interferon works by immunomodulation, but is successful in less than a third of treated patients and is a relatively weak antiviral. NAs directly suppress the hepatitis B virus but have limited durability. Based on current data, combination of NA and interferon results in greater viral suppression but does not translate to off-treatment sustained response. Concomitant or sequential treatment also does not make a difference. Combining telbivudine and interferon also runs the risk of severe peripheral neuropathy. On the other hand, interferon switch or additional therapy in patients well controlled with NAs appears to improve the durability of off-treatment response. This article reviews current data on interferon and NA combination and discusses potential future developments.

Hand hygiene and risk of influenza virus infections in the community: a systematic review and meta-analysis.

Community-based prevention strategies for seasonal and pandemic influenza are essential to minimize their potential threat to public health. Our aim was to evaluate the efficacy of hand hygiene interventions in reducing influenza transmission in the community and to investigate the possible modifying effects of latitude, temperature and humidity on hand hygiene efficacy. We identified 979 articles in the initial search and 10 randomized controlled trials met our inclusion criteria. The combination of hand hygiene with facemasks was found to have statistically significant efficacy against laboratory-confirmed influenza while hand hygiene alone did not. Our meta-regression model did not identify statistically significant effects of latitude, temperature or humidity on the efficacy of hand hygiene. Our findings highlight the potential importance of interventions that protect against multiple modes of influenza transmission, and the modest efficacy of hand hygiene suggests that additional measures besides hand hygiene may also be important to control influenza.

Gestational diabetes mellitus in five ethnic groups: a comparison of their clinical characteristics.

AIMS: The prevalence of gestational diabetes mellitus has been shown to vary between ethnic groups. The differences in the clinical characteristics and outcomes of women with gestational diabetes mellitus from various ethnic groups have not been clearly defined. METHODS: A retrospective review of women with gestational diabetes mellitus from a single institution between 2007 and 2010 was conducted. The clinical profiles of women from five ethnic groups (South-East Asian, South Asian, Middle Eastern, Anglo-European and Pacific Islander) were documented, including the outcomes of their pregnancy. RESULTS: In this cohort of 827 women from these five ethnic groups, South-East Asians had the lowest BMI, lowest fasting (yet highest 2-h) glucose level on 75-g glucose tolerance test, lowest need for insulin therapy and lowest rate of macrosomia. South Asians had the lowest parity but strongest family history of diabetes. Their offspring also had the lowest birthweight. Women from Pacific Islands had the highest parity, BMI, fasting glucose levels on 75-g glucose tolerance test, HbA(1c) (at diagnosis of gestational diabetes mellitus as well as at 36 weeks' gestation) and greatest need for insulin therapy. Their offspring also had the highest birthweights. CONCLUSION: This study highlighted the significant differences in clinical characteristics of women with gestational diabetes mellitus among five ethnic groups. These differences may need to be considered in the management of gestational diabetes mellitus, especially in the interpretation of normality for pregnancy.

Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection.

The study investigated the hepatitis B virus (HBV) genotypic resistance profile in 1803 nucleos(t)ide analogue (NA)-experienced Chinese patients with chronic HBV infection. Serum HBV DNA was extracted, and the reverse transcriptase region was analysed by a high-sensitive direct PCR sequencing and verified by clonal sequencing if necessary. Drug-resistant mutations were detected in 560 of the 1803 patients, including 214 of 490 patients who received lamivudine (LAM), 35 of 428 patients who received adefovir (ADV), five of 18 patients who received telbivudine and 306 of 794 patients who received various sequential/combined NA therapies. ADV-resistant mutations were detected in 36 of 381 patients who received LAM and then switched-to ADV in contrast to one of 82 patients who received ADV add-on LAM. Entecavir (ETV)-resistant mutations were detected not only in LAM- and ETV-treated patients but also in LAM-treated ETV-naïve patients. Double mutations rtM204I and rtL180M were detected more frequently in genotype C than in genotype B virus, and patients infected with this mutant had higher alanine transaminase levels than those infected with mutant containing the rtM204I substitution alone. Multidrug-resistant HBV strains were identified in eight patients, including two novel strains with mutational patterns rtL180M + A181V + S202G + M204V + N236T and rtL180M + S202G + M204V + N236T. The results provide new information on HBV genotypic resistance profiles in a large cohort of Chinese patients with chronic HBV infection and may have important clinical implication for HBV drug resistance management in China.

Outside of the intensive care unit: the safety and effectiveness of an insulin-dextrose infusion protocol.

A review of patients who were on an insulin-dextrose (I-D) infusion protocol in general hospital wards over a 6-month period was conducted to compare glycaemic control before, during and following I-D infusion. Among the 34 cases identified, blood glucose levels during the period of I-D infusion were significantly better than those before or after I-D infusion. This I-D infusion protocol was shown to be effective and safe in maintaining good glycaemic control for patients outside intensive care unit.

PPARgamma is essential for protection against nonalcoholic steatohepatitis.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates lipid metabolism and inflammatory responses. Certain PPARgamma ligands improve nonalcoholic steatohepatitis (NASH). The role of PPARgamma itself in NASH remains poorly understood. The functional consequences of PPARgamma in the development of steatohepatitis through gene deficiency or gene overexpression of PPARgamma delivered by adenovirus (Ad-PPARgamma) were examined. Our results show that PPARgamma-deficient (PPARgamma(+/-)) mice fed the methionine- and choline-deficient (MCD) diet developed more severe steatohepatitis than wild-type mice, and were unaffected by PPARgamma ligand rosiglitazone. Overexpression of PPARgamma delivered by Ad-PPARgamma attenuated steatohepatitis. This effect was associated with redistribution of fatty acid from liver to adipose tissue by enhancing expression of fatty acid uptake genes (fatty acid binding protein-4 (aP2), fatty acid translocase (CD36), lipoprotein lipase (LPL) and fatty acid transport protein-1 (FATP-1)) and lipogenic genes (sterol regulatory element binding protein isoform-1 (SREBP-1) and stearoyl-CoA desaturase isoform-1 (SCD-1)) in adipose tissue and to a lesser extent in liver. The anti-steatohepatitis action of PPARgamma was also mediated via regulating adipokines through suppressing tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and inducing adiponectin. Moreover, PPARgamma activation suppressed hepatic lipoperoxide and reduced hepatic pro-inflammatory cytokines (TNF-alpha and IL-6) production. In conclusion, PPARgamma is an important endogenous regulator and potential therapeutic target for nutritional steatohepatitis.

Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B.

Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B.

BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo.

Hepatic oxidative stress plays a critical role in metabolic forms of steatohepatitis. Phyllanthus urinaria, an herbal medicine, has been reported to have potential antioxidant properties. We tested the effects of P. urinaria on nutritional steatohepatitis both in vitro and in vivo. Immortalized normal hepatocytes (AML-12) or primary hepatocytes were exposed to control, the methionine-and-choline-deficient (MCD) culture medium, in the presence or absence of P. urinaria for 24 hours. Hepatocyte triglyceride, release of alanine aminotransferase, lipoperoxides, and reactive oxygen species production were determined. Age-matched C57BL/6 and db/db mice were fed control or MCD diet for 10 days with or without P. urinaria. Hepatic steatosis, necroinflammation, triglycerides, and lipid peroxide levels were determined. Hepatic expression of inflammatory factors and lipid regulatory mediators were assayed. P. urinaria reduced steatosis and alanine aminotransferase (ALT) levels in culture of hepatocytes in a dose-dependent manner. Phyllanthus prevented MCD-induced hepatic fat accumulation and steatohepatitis in mice. This effect was associated with repressed levels of hepatic lipid peroxides, reduced expression of cytochrome P450-2E1, pro-inflammatory tumor necrosis factor alpha, interleukin-6, dampened activation of inflammatory c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-kappaB), increased expression of lipolytic cytochrome P450 (Cyp4a10), and suppressed transcriptional activity of lipogenic CCAAT/enhancer binding protein beta (C/EBPbeta). Hepatic acyl co-enzyme A oxidase that regulated hepatic beta-oxidation of fatty acid and other lipid regulators were not affected by P. urinaria. In conclusion, P. urinaria effectively alleviated the steatohepatitis induced by the MCD, probably through dampening oxidative stress, ameliorating inflammation, and decreasing lipid accumulation.