Background: Identifying risk factors for the development of complications of chronic hepatitis B (CHB) is important for setting up treatment criteria. Aim: To determine risk factors for the development of complications in Asian CHB patients. Patients and methods: A total of 3233 Chinese CHB patients (mean follow up 46.8 months) were monitored for liver biochemistry, viral serology, hepatitis B virus (HBV) DNA levels, acute exacerbation, hepatitis B e antigen (HBeAg) seroconversion, and development of cirrhotic complications and hepatocellular carcinoma. Results: Median age for HBeAg seroconversion and development of complications was 35 years and 57.2 years, respectively. Patients with alanine aminotransferase (ALT) levels of 0.5-1 times the upper limit of normal (ULN) and 1-26 ULN had an increased risk for the development of complications compared with patients with ALT levels ,0.56 ULN (p,0.0001 for both). HBeAg/antibody to hepatitis B e antigen status, and number of episodes, duration, and peak ALT levels of acute exacerbations were not associated with an increased risk of complications. In patients with complications, 43.6% had HBV DNA levels less than 1.42610 5 copies/ml. Male sex, stigmata of chronic liver disease, old age, low albumin, and high a fetoprotein levels on presentation were independently associated with increased cumulative risk of complications. Male sex, presence of hepatitis symptoms, old age, low albumin level, and presence of complications on presentation were independently associated with shorter survival. Conclusion: Prolonged low level viraemia causing insidious and continual liver damage, as reflected by ALT levels of 0.5-26 ULN, is the most likely pathway for the development of complications in Asian CHB patients.

From 1996 to 1998, listed companies in China were required to achieve a minimum return on equity (ROE) of 10 percent in each of the previous three years before they could apply for permission to issue additional shares. As a result of this rule, there was a heavy concentration of ROEs in the area just above 10 percent. We show that the Chinese regulators appear to have scrutinized firms using excess amounts of nonoperating income to reach the 10 percent hurdle. In addition, their ability to do so seems to have improved over time, which allows them to be better able to identify firms that subsequently performed better. However, many firms were still able to gain rights issue approval through excess nonoperating income. We show that these firms subsequently underperformed other approved firms that did not use the same practice, indicating that the Chinese regulators' objective of guiding capital resources toward the well-performing sectors is partially compromised by earnings management.

a b s t r a c tUsing a sample of 185 Chinese IPO firms listed on the Shanghai Stock Exchange during the period 1999-2001, we show that related-party (RP) sales of goods and services could be used opportunistically to manage earnings upwards in the pre-IPO period. We also provide evidence that such behavior may be motivated by the prospect of tunneling opportunities in the post-IPO period, i.e., exploiting economic resources from minority shareholders for the benefit of the parent company. We provide evidence of one such opportunistic tunneling tool: non-repayment by Chinese parent companies of net outstanding corporate loans made to them by their newly listed subsidiaries. Furthermore, we provide evidence in support of our assertion of an association between such tunneling behavior in the post-IPO period and earnings management via abnormal RP sales in the pre-IPO period. Finally, we demonstrate the apparent failure of investors in Chinese IPOs to perceive the link between the two phenomena. The results enhance 0278-4254/$ -see front matter Ó journal homepage: www.elsevier.com /locate/jaccpubpol understanding of the motives for and consequences of earnings manipulation during the IPO process. They highlight a potential additional investment risk facing foreign investors in China's capital markets as well as in Chinese firms cross-listed in non-Chinese stock exchanges, and have policy implications for China and other emerging markets which need to improve the protection of minority shareholders' rights.

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add‐on liraglutide, sitagliptin, or insulin glargine in this 26‐week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging–estimated proton density fat fraction (MRI‐PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent‐to‐treat population. MRI‐PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI‐PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI‐PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.

Few studies have examined Chinese patients with chronic hepatitis B who exhibit hepatitis B surface antigen (HBsAg) seroclearance. We comprehensively studied the biochemical, virological, histological, and clinical aspects of 92 patients with HBsAg seroclearance (median follow-up, 126 months). Ninety-two HBsAg-positive controls matched for age, sex, and duration of follow-up were also recruited. Liver biochemistry, serum hepatitis B virus (HBV) DNA levels, and development of clinical complications were monitored. Intrahepatic total and covalently closed circular (ccc) HBV DNA were measured quantitatively in 16 patients. HBV genotype was determined in 30 patients. The mean age at HBsAg seroclearance was 48.8 (؉ 13.81) years. There was a significant improvement in serum alanine aminotransferase levels after HBsAg seroclearance (p<0.0001). Patients with genotype B had a higher chance of HBsAg seroclearance than those with genotype C (P ‫؍‬ .014). Ninety-eight percent of patients had undetectable serum HBV DNA. Thirty-seven percent of patients had low titer of intrahepatic HBV DNA, mainly in the form of cccDNA (71%-100%). All 14 patients with liver biopsies had near normal histology. There was no difference in the risk of development of hepatocellular carcinoma (HCC) between patients with and without HBsAg seroclearance. However, the mean age of HBsAg seroclearance was significantly older in patients with HCC than in patients without HCC (P ‫؍‬ .016). In conclusion, patients with HBsAg seroclearance had favorable biochemical, virological, and histological parameters. Intrahepatic HBV DNA level was low and predominantly in the form of cccDNA. However, HCC could still develop, particularly in patients with cirrhosis who had HBsAg seroclearance at an older age. (HEPATOLOGY 2004;39:1694 -1701.) H epatitis B surface antigen (HBsAg) seroclearance is a rare event in Chinese patients with chronic hepatitis B virus (HBV) infection who acquire the disease early in life. The estimated annual incidence of HBsAg seroclearance is 0.1% to 0.8%. 1,2 Undetectable HBsAg in the serum is usually due to a decrease in viremia rather than the emergence of HBsAg mutants. 3 Some studies demonstrate a favorable outcome in terms of histological features and development of hepatocellular carcinoma (HCC). 2,4 However, these findings are not confirmed by other studies. 5,6 The presence of HBV DNA within the liver in patients with HBsAg seroclearance has been demonstrated in some studies, 7-9 but it is not known whether the intrahepatic HBV DNA is replicative or nonreplicative-that is, in the form of covalently closed circular (ccc) DNA. Also, it is uncertain how much residual virus is in extrahepatic reservoirs like peripheral blood mononuclear cells (PBMC).Therefore, we sought to determine the factors associated with and the significance of HBsAg seroclearance in Chinese HBV patients by examining the following parameters: (1) liver biochemistry, (2) HBV DNA in the serum and PBMC, (3) HBV genotypes, (4) intrahepatic total and cccDNA, (5) liver h...

The pathologic role of hepatitis B virus (HBV) genotype in Chinese patients with HBV infection is largely unknown. We examined the relationship between HBV genotypes, and hepatitis B e antigen (HBeAg) seroconversion, acute exacerbation, cirrhosis-related complications, and precore/core promoter mutations. Three hundred forty-three HBV patients (288 were asymptomatic, 55 presented with cirrhosis-related complications) were recruited. HBV genotypes and precore/core promoter mutations were determined by line probe assays. Genotypes B and C were the 2 most common genotypes, contributing 28% and 60%, respectively. The median age of HBeAg seroconversion for patients with genotype B was 9 years earlier than patients with genotype C (P ‫؍‬ .011). There were no differences in the liver biochemistry, HBV DNA level, and cumulative risk of acute exacerbation (defined as increased alanine aminotransferase level >1.5 ؋ upper limit of normal) between patients with genotypes B and C. There was a trend for patients with genotype B to have a higher cumulative rate of HBeAg seroconversion compared with patients with genotype C at the initial follow-up of 6 years (P ‫؍‬ .053), but this difference became insignificant during subsequent follow-up. The prevalence of both genotypes was the same in patients with and without cirrhosis-related complications and/or hepatocellular carcinoma. Genotype B was associated with precore mutations (P < .0001), whereas genotype C was associated with core promoter mutations (P < .0001). In conclusion, although patients with genotype B had earlier HBeAg seroconversion, there was no significant reduction in the risk of development of complications. Genotypes B and C are associated with high prevalence of precore and core promoter mutations, respectively. (HEPATOLOGY 2003;37:562-567.) S eventy-five percent of the estimated 400 million patients with chronic hepatitis B virus (HBV) infection in the world are Asians. 1,2 Genotypes B and C are the 2 most common genotypes prevailing in Asia. 3,4 The role of HBV genotype has been examined by several studies, suggesting that genotype C is associated with a lower rate of hepatitis B e antigen (HBeAg) seroconversion and more serious liver disease compared with genotype B. 3,[5][6][7][8][9] Further studies are required to address the apparently more deleterious effects of genotype C. Another reason for investigation is the relationship between HBV genotypes and precore and core promoter mutations. Some studies have shown that core promoter mutations occur predominantly with genotype C, whereas others have suggested that precore mutations may be more common with genotype B. 9-12 Confirmatory studies are required. Furthermore, the effect of HBV genotypes on the chance of acute exacerbation and HBeAg seroconversion has not been fully examined in a longitudinal manner. There is only one recent study that demonstrates that patients with genotype B have a higher cumulative rate of HBeAg seroconversion compared with patients with genotype C. 8 The primary aim of this st...

BackgroundCalorie restriction (CR), which has a potent anti-inflammaging effect, has been demonstrated to induce dramatic changes in the gut microbiota. Whether the modulated gut microbiota contributes to the attenuation of inflammation during CR is unknown, as are the members of the microbial community that may be key mediators of this process.ResultsHere, we report that a unique Lactobacillus-predominated microbial community was rapidly attained in mice within 2 weeks of CR, which decreased the levels of circulating microbial antigens and systemic inflammatory markers such as tumour necrosis factor alpha (TNF-α). Lactobacillus murinus CR147, an isolate in the most abundant operational taxonomic unit (OTU) enriched by CR, downregulated interleukin-8 production in TNF-α-stimulated Caco-2 cells and significantly increased the lifespan and the brood size of the nematode Caenorhabditis elegans. In gnotobiotic mice colonized with the gut microbiota from old mice, this strain decreased their intestinal permeability and serum endotoxin load, consequently attenuating the inflammation induced by the old microbiota.ConclusionsOur study demonstrated that a strain of Lactobacillus murinus was promoted in CR mice and causatively contributed to the attenuation of ageing-associated inflammation.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0440-5) contains supplementary material, which is available to authorized users.

Background and aim: Clinical data on spontaneous hepatitis B e antigen (HBeAg) seroconversion and acute exacerbation of chronic hepatitis B (CHB) virus infection from large population studies are lacking. In the present study we examined the clinical features and significance of HBeAg seroconversion and acute exacerbation in 3063 Chinese CHB patients. Methods: Clinical assessment, liver biochemistry, hepatitis B virus (HBV) serology and HBV DNA, time of HBeAg seroconversion, and acute exacerbation were monitored. Results: Median age at HBeAg seroconversion was 34.5 years. The cumulative HBeAg seroconversion rate significantly increased with alanine aminotransferase (ALT) levels on presentation (p<0.0001). For patients with ALT levels more than twice the upper limit of normal (ULN) on presentation, the HBeAg seroconversion rate at the fifth year of follow up was 72.4%. After HBeAg seroconversion, 65.2% (73/110) of patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay. Of these, 78.1% still had HBV DNA levels detectable by the Amplicor HBV Monitor Test. We found that 37.5% antibody to HBeAg (anti-HBe) positive patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay before acute exacerbation. Acute exacerbations of longer duration, with higher peak ALT, bilirubin, and α fetoprotein levels were associated with an increased HBeAg seroconversion rate (p<0.0001-0.045). Acute exacerbation with peak ALT levels more than five times the ULN carried a 46.4% chance of HBeAg seroconversion within three months. HBeAg seroreversion and mortality occurred in 2.7% and 0.7% of acute exacerbations, respectively. Conclusion: In the present study we have provided information on HBeAg seroconversion and acute exacerbation, which are important in decision making for CHB treatment and in designing clinical trials.