Chronic hepatitis B is caused by persistent infection with the hepatitis B virus (HBV), a unique DNA virus that replicates through an RNA intermediate produced from a stable covalently closed circular DNA molecule. Viral persistence appears to be due to inadequate innate and adaptive immune responses. Chronic infection has a variable course after several decades resulting in cirrhosis in up to one‐third of patients and liver cancer in a proportion of those with cirrhosis. Sensitive assays for HBV DNA levels in serum have been developed that provide important insights into pathogenesis and natural history. Therapy of hepatitis B is evolving. Peginterferon induces long‐term remissions in disease in one‐third of patients with typical hepatitis B e antigen (HBeAg) positive chronic hepatitis B, but a lesser proportion of those without HBeAg. Several oral nucleoside analogues with activity against HBV have been shown to be effective in suppressing viral levels and improving biochemical and histological features of disease in a high proportion of patients with and without HBeAg, at least in the short term. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Long‐term therapy with nucleoside analogues may be the most appropriate approach to treatment, but the expense and lack of data on long‐term safety and efficacy make recommendations difficult. Clearly, many basic and clinical research challenges remain in defining optimal means of management of chronic hepatitis B. (HEPATOLOGY 2007;45:1056–1075.)

Management of hepatitis B: Summary of a clinical research workshop Potential conflict of interest: Dr. Lok is a consultant and received grants from GlaxoSmithKline, Bristol-Myers Squibb, Idenix, Gilead, Roche, and Innogenetics.

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

Summary Background Despite the existence of effective prevention and treatment interventions, hepatitis B virus (HBV) infection continues to cause nearly 1 million deaths each year. WHO aspires to global control and elimination of HBV infection. We aimed to evaluate the potential impact of public health interventions against HBV, propose targets for reducing incidence and mortality, and identify the key developments required to achieve them. Methods We developed a simulation model of the global HBV epidemic, incorporating data on the natural history of HBV, prevalence, mortality, vaccine coverage, treatment dynamics, and demographics. We estimate the impact of current interventions and scaling up of existing interventions for prevention of infection and introducing wide-scale population screening and treatment interventions on the worldwide epidemic. Findings Vaccination of infants and neonates is already driving a large decrease in new infections; vaccination has already prevented 210 million new chronic infections by 2015 and will have averted 1·1 million deaths by 2030. However, without scale-up of existing interventions, our model showed that there will be a cumulative 63 million new cases of chronic infection and 17 million HBV-related deaths between 2015 and 2030 because of ongoing transmission in some regions and poor access to treatment for people already infected. A target of a 90% reduction in new chronic infections and 65% reduction in mortality could be achieved by scaling up the coverage of infant vaccination (to 90% of infants), birth-dose vaccination (to 80% of neonates), use of peripartum antivirals (to 80% of hepatitis B e antigen-positive mothers), and population-wide testing and treatment (to 80% of eligible people). These interventions would avert 7·3 million deaths between 2015 and 2030, including 1·5 million cases of cancer deaths. An elimination threshold for incidence of new chronic infections would be reached by 2090 worldwide. The annual cost would peak at US$7·5 billion worldwide ($3·4 billion in low-income and lower-middle-income countries), but decrease rapidly and this would be accelerated if a cure is developed. Interpretation Scale-up of vaccination coverage, innovations in scalable options for prevention of mother-to-child transmission, and ambitious population-wide testing and treatment are needed to eliminate HBV as a major public health threat. Achievement of these targets could make a major contribution to one of the Sustainable Development Goals of combating hepatitis. Funding Medical Research Council.

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Requirements for global elimination of hepatitis B: a modelling study

Obstetrics and gynaecology.

The guideline of prevention and treatment for chronic hepatitis B (2010 version)

Hepatitis B is a major health concern in the Asia-Pacific region, and is endemic in China, Southeast Asia, and Africa. Chronic hepatitis B virus (HBV) infection may cause hepatic cirrhosis and liver cancer. It is estimated that there are more than 350 million chronic HBV carriers worldwide, of whom approximately one quarter will die of chronic hepatitis B-related liver diseases. HBV is transmitted horizontally through blood and blood products or by sexual transmission, and vertically from mother to infant. Perinatal infection is the predominant mode of transmission in countries with a high prevalence of hepatitis B surface antigen (HBsAg) carriage, and perinatal transmission leads to high rates of chronic infection. Therefore, it is important to prevent the mother-to-child transmission (MTCT) of HBV. Research has shown that pregnant women with high HBV DNA levels have an increased risk of MTCT. However, most of the obstetrics guidelines do not make a distinction between pregnant women with high HBV DNA levels and those who are HBsAg positive only. This review addresses the management of pregnant women with high levels of HBV viremia, in terms of antiviral therapy, use of hepatitis B immunoglobulin (HBIG), the combined application of hepatitis B vaccine and HBIG, choice of delivery mode and feeding practices.

Individualized management of pregnant women with high hepatitis B virus DNA levels.

AIM To compare smooth muscle cells, type I collagen, and apoptosis of the lower uterine segment of women who had/without a prior cesarean delivery METHODS Alpha smooth muscle actin (α-SMA), type I collagen, and nuclear apoptosis were compared between the groups from lower uterine segment Twenty-eight controls and 82 with one prior cesarean delivery were included The women with a prior cesarean section were classified by time since the surgery: ≤3 years, >3 and ≤5 years, >5 and ≤7 years, >7 and ≤9 years, and >9 years RESULTS Smooth muscle volume density (VD) % was significantly lower in women who had cesarean sections in first three groups than in the controls (all, P<001) Type I collagen VD% was similar among all groups and the controls The number of apoptotic nuclei in the lower uterine segment of the scarred group was greater up to 3 years after surgery and less than in the control at 7-9 years The number of non-apoptotic nuclei in the scarred group was greater than controls up to 7 years after surgery CONCLUSION The lower uterine segment scar becomes stable at 3 years after cesarean delivery, and by 9 years, the scar is mature

A preliminary study of uterine scar tissue following cesarean section.

The consumption of probiotics and fermented foods has been very popular in recent decades. The primary aim of our study was to evaluate the effect of probiotics on the gut microbiota and the changes in inflammatory cytokines after an average of 6.7 weeks of probiotic administration among normal pregnant women. Thirty-two healthy pregnant women at 32 weeks of gestation were recruited and divided into two groups. The probiotic group ingested combined probiotics until after birth. The base characteristics of the probiotics and control groups showed no significant differences. The structure of the fecal microbiota at the genus level varied during the third trimester, and administration of probiotics had no influence on the composition of the fecal microbiota however, many highly abundant taxa and core microbiota at the genus level changed in the probiotic group when compared to the control group. The analysis of cytokines showed that IL-5, IL-6, TNF-α, and GM-CSF had equal levels between the baseline and control groups but were significantly increased after probiotic administration (baseline = control < probiotics). Additionally, levels of IL-1β, IL-2, IL-12, and IFN-γ significantly increased among the three groups (baseline < control < probiotics). This result demonstrated that probiotics helped to shift the anti-inflammatory state to a pro-inflammatory state. The correlation analysis outcome suggested that the relationship between the microbiota and the cytokines was not strain-dependent. The gut microbiota varied during the third trimester. The probiotics demonstrated immunomodulation effects that helped to switch over to a pro-inflammatory immune state in the third trimester, which was important for labor.

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Probiotic Supplementation During Human Pregnancy Affects the Gut Microbiota and Immune Status.

The present study was conducted to evaluate new methods to repair the reproductive function of the oviduct, thereby allowing gametes to combine and grow in vivo under natural circumstances. Sixty pathogen-free female New Zealand rabbits were divided into three groups: a wild-type group, an untreated control group, and a treatment group. Disposable sterile newborn sputum suction tubes were inserted into the urogenital tract to instill an Escherichia coli suspension into the uterine cavity to establish the chronic salpingitis model. Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) or normal saline were used to treat this infection via different methods. The therapeutic effect was assessed by evaluating morphology, inflammatory factors, proteinology, and pregnancy outcomes. Oviducts of New Zealand rabbits in the untreated control group showed structural failure and abnormal supermicrostructure of epithelial cells. WJMSCs could partially repair the structure and supermicrostructure of the tubal epithelium. The concentration of tumor necrosis factor (TNF)-α in the untreated control group was significantly higher than that in the wild-type group (P = 0.015). The concentration of TNF-α in the local treatment group was significantly lower than that in the untreated control group (P = 0.011). The expression of oviductal glycoprotein (OVGP) and OVGP mRNA in the wild-type group was significantly higher than those in the untreated control group (P = 0.024 and P = 0.013, respectively). The litter size of the treatment group was 2 ± 2.39 kits, which was higher than that of the untreated control group (P = 0.035). Chronic inflammation can destroy the structure of the oviduct and the supermicrostructure of epithelial cells as well as leading to infertility. WJMSC transplantation therapy in rabbits with chronic salpingitis partially restored fertility. WJMSCs also repaired the structure of the tubal epithelium subjected to chronic inflammation, decreased the level of inflammatory factors, and partially restored the secretion level of OVGP.

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Treatment evaluation of Wharton’s jelly-derived mesenchymal stem cells using a chronic salpingitis model: an animal experiment

To study the effect of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) on the rat salpingitis model, 50 female Wistar rats were randomly divided into one control and five model groups. Mixed bacteria were injected into the oviducts of model groups. The treated acute and chronic groups received intraperitoneal injections of WJMSCs (1 x 10(6)) once a week for three weeks. Serum inflammation factor, collagen fiber content and oviduct-specific glycoprotein (OVGP) levels were detected in control, chronic, ex-treatment acute and chronic, and treated acute and chronic groups (N = 5 for each group). Pregnancy rate and litter size of control, chronic, treated acute and treated chronic groups were compared. Serum TNF-α and INF-γ levels increased in ex-treatment acute and chronic groups, and restored to normal in the acute treated group but not in the treated chronic group. Oviduct collagen fibers did not increase significantly before or after treatment in the acute group, but it increased in the ex-treatment chronic group and did not improve after treatment. After treatment, OVGP levels restored to normal in the acute group but reduced in the ex-treatment and treated chronic groups and chronic group. The pregnancy rate and litter size of the treated acute group recovered to normal, but in the treated chronic group and chronic model group, they decreased significantly. Thus, intraperitoneal injection of WJMSCs could recover the function of the oviduct in acute salpingitis rats, but its effect on chronic salpingitis was poor. Timely treatment of salpingitis is crucial to preserve reproductive function.

https://www.funpecrp.com.br/gmr/year2015/vol14-2/pdf/gmr5336.pdf

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis.

Xiaomin Xiao

Papers

Individualized management of pregnant women with high hepatitis B virus DNA levels.

A preliminary study of uterine scar tissue following cesarean section.

Probiotic Supplementation During Human Pregnancy Affects the Gut Microbiota and Immune Status.

Treatment evaluation of Wharton’s jelly-derived mesenchymal stem cells using a chronic salpingitis model: an animal experiment

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis.