Natural killer cells play an important role in virus infection control: Antiviral mechanism, subset expansion and clinical application.

With the global spread of coronavirus disease 2019 (COVID-19), the important role of natural killer (NK) cells in the control of various viral infections attracted more interest, via non-specific activation, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and activating receptors, as well as specific activation, such as memory-like NK generation. In response to different viral infections, NK cells fight viruses in different ways, and different NK subsets proliferate. For instance, cytomegalovirus (CMV) induces NKG2C + CD57 + KIR+ NK cells to expand 3-6 months after hematopoietic stem cell transplantation (HSCT), but human immunodeficiency virus (HIV) induces KIR3DS1+/KIR3DL1 NK cells to expand in the acute phase of infection. However, the similarities and differences among these processes and their molecular mechanisms have not been fully discussed. In this article, we provide a summary and comparison of antiviral mechanisms, unique subset expansion and time periods in peripheral blood and tissues under different conditions of CMV, HIV, Epstein-Barr virus (EBV), COVID-19 and hepatitis B virus (HBV) infections. Accordingly, we also discuss current clinical NK-associated antiviral applications, including cell therapy and NK-related biological agents, and we state the progress and future prospects of NK cell antiviral treatment.

Prevalence of hepatitis B and C virus co-infection in HIV positive patients attending a health institution in southeast Nigeria.

BACKGROUND: The health of people living with HIV/AIDS becomes progressively worse when co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), resulting in shortened life span. The modes of transmission of HIV, HBV and HCV are similar. OBJECTIVE: To determine the prevalence of HBV and HCV co-infection in HIV patients. METHOD: This was a retrospective study of serology test results for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) of HIV positive patients registered from 2008-2013 (6years) at the University of Nigeria Teaching Hospital. Adult patients with confirmed HIV seropositivity were included. Ethical approval was obtained and confidentiality of the patient information was maintained. Laboratory records were reviewed to obtain HBsAg, anti-HCV, and CD4 T-lymphocyte results. Prevalence was determined by the number of positive results over total number of patients tested. Chi-square test was used to determine relationships and p<0.05 was considered to be statistically significant. RESULTS: 4663 HIV patient records were included comprising 3024 (65%) females and 1639 (35%) males. Serology results showed 365/4663 (7.8%) tested HBsAg-positive only; 219/4663 (4.7%) tested anti-HCV-positive only; and 27/4663 (0.58%) tested both HBsAg and anti-HCV-positive. Correlation of age and sex were statistically significant with HBV and HCV (p<0.05) but not CD4 count (p>0.05). CONCLUSION: HBV co-infection was more prevalent than HCV, and triple infection was also observed. Screening for these viral infections in the HIV population is necessary for early identification to enable appropriate, holistic management of these patients.

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients.

BACKGROUND: The impact of hepatitis virus infection on arterial calcification (AC) was not studied. OBJECTIVE: To study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. CASES AND METHODS: 172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. RESULTS: 86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group. In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P<0.001 in all). HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6±0.66 vs. 5.45±0.77mg/dL, 36.4±7.2 vs. 44.1±8.69, and 348±65.4 vs. 405.9±83.2pg/mL, P<0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group. CONCLUSION: HCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.

Anti-Hepatitis B Virus Activity of Esculetin from Microsorium fortunei In Vitro and In Vivo.

Coumarins are widely present in a variety of plants and have a variety of pharmacological activities. In this study, we isolated a coumarin compound from Microsorium fortunei (Moore) Ching; the compound was identified as esculetin by hydrogen and carbon spectroscopy. Its anti-hepatitis B virus (HBV) activity was investigated in vitro and in vivo. In the human hepatocellular liver carcinoma 2.2.15 cell line (HepG2.2.15) transfected with HBV, esculetin effecting inhibited the expression of the HBV antigens and HBV DNA in vitro. Esculetin inhibited the expression of Hepatitis B virus X (HBx) protein in a dose-dependent manner. In the ducklings infected with duck hepatitis B virus (DHBV), the levels of DHBV DNA, duck hepatitis B surface antigen (DHBsAg), duck hepatitis B e-antigen (DHBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly after esculetin treatment. Summing up the above, the results suggest that esculetin efficiently inhibits HBV replication both in vitro and in vivo, which provides an opportunity for further development of esculetin as antiviral drug.

Alternative treatment in Hepatitis B by using polyherbal formulation.

The hepatitis B is most prevalent diseases (along with morbidities) in Asian countries. This research study has been conducted to provide an alternative treatment which is safe, effective and cost-effective to comprehend relations of disease, symptoms, patients response and the clinical response via better management of hepatitis B. The goal of this research is to evaluate efficacy and safety of herbal medicine as compared to allopathic medicine in patients suffering from hepatitis B. This was a single blind, randomized controlled clinical trial conducted at Shifa-ul-Mulk Memorial Hospital Hamdard University, Karachi and Dar ul Shifa Unani Dawakhana Karachi, Pakistan. The patients of both genders ranging from 25 to 50 years with symptoms and diagnosed for hepatitis B that fulfilled the criteria for membership, and consented for participation were registered. Ethical committee clearance and permission was obtained from the concerned committee at Faculty of Eastern Medicine, Hamdard University, Karachi, Pakistan. No significant difference was identified after treatment and it was found that the efficacy of Alpha (Control drug) is same as Safoof akseer e jigar (Test drug). The data offered support to the null hypothesis and therefore research hypothesis was rejected. According to the statistical analysis by chi square, hepatitis B was recorded as negative in 26 patients (57.77%) out of 45 patients by the use of Interferon Alpha (control therapy) and in 27 patients (64.28%) out of 42 patients by the use of Safoof akseer e jigar (test drug). Comparison of the data recorded of the patients was determined as both drugs showed significant improvement and p value>0.05. The efficacy response is equal in both drugs while test drug showed more safety response. It is concluded that Safoof akseer e jigar possesses as effective a therapeutic value in treating hepatitis B as allopathic medicine.

HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa.

BACKGROUND: Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa. METHODS: Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS: Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS: HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates.

[Study on health-seeking behavior and influencing factors among Chinese hepatitis B surface antigen positive adults].

OBJECTIVE: To analyze the characteristics of health-seeking behaviors and related influencing factors of the community-based hepatitis B surface antigen (HBsAg) positive adults, in China. METHODS: Based on the cohort formed by the HBsAg positive patients, in the national sero-survey project in 2006, we conducted a follow-up programs in 2010 and 2014. In the latest follow-up project, we carried out a cross-sectional study to collect information on health-seeking behaviors of the patients. Questionnaires would include information on clinic visits, diagnosis, regular physical examination and treatments,etc. We used the SPSS 18.0 software for data analysis. RESULTS: Totally, 2 478 HBsAg positive adults (≥18 years old) were followed through, with 34.4% (853/2 478) of them had visited the doctors and diagnosed after they were informed the status of HBsAg positivity, in the 2006-sero-survey program. Among patients who ever visiting the clinic, 51.2% (372/727) of them underwent at least medical examination once a year, with 31.5% (229/727) of them received treatment. Furthermore, 34.5% (79/229) of the treated patients adopted the traditional Chinese medicine or medicine for ' liver protection'. 56.8% (130/229) of the treated patients received antiviral drugs. Data from the binary logistic regression showed that the major influencing factors on clinic visits would include: age, level of education received and residencial areas (rural/urban). CONCLUSIONS: Consciousness on health was low in those community-based HBsAg positive people. Standerdized management and clinical treatment programs should be set up accordingly.

Synergistic effect of magnetite and gold nanoparticles onto the response of a label-free impedimetric hepatitis B virus DNA biosensor.

A magnetite and gold nanoparticle modified carbon paste electrode (CPE) was prepared for the immobilization of a thiol modified Hepatitis B virus (HBV) probe DNA and determination trace amount of target HBV DNA. Indeed, the sensing platform integrated two nanoparticles that had previously been employed individually in the DNA biosensors. The proposed DNA biosensor could measure target HBV DNA virus concentration with a low detection limit of 3.1 (±0.1)×10-(13)M, which was greatly lower than the detection limit reported with gold or magnetite nanoparticles alone. The change of interfacial charge transfer resistance (RCT) was confirmed the hybrid formation between probe and target HBV DNA. The RCT difference (before and after hybridization with the target HBV DNA) was in a linear relationship with the logarithm of complementary oligonucleotide concentrations in the range of 8.3 (±0.1)×10(-13) to 6.4 (±0.2)×10(-7)M. In addition, the novel methodology for specific DNA sequence detection was highly selective, repeatable, and reproducible. Finally, this work was successfully utilized for the sensitive and label free impedimetric determination of HBV target DNA in the urine and blood plasma samples.

Maternal zinc supplementation improves hepatitis B antibody responses in infants but decreases plasma zinc level.

PURPOSE: The World Health Report identifies zinc deficiency as one of the major causes of disease in developing countries, and infants are at particular risk. We aimed to investigate the effect of maternal zinc supplementation on the infant's immune function in a population at risk of deficiency. METHODS: In a randomized, double-blind placebo-controlled trial, mothers were supplemented either with 20 mg/day of elemental zinc (n = 20) or placebo (n = 19) at the beginning of second trimester, which continued until 6 months postpartum. Indicators of the infants' immune function measured included interleukin (IL)-7, thymic size and response to hepatitis B vaccination. RESULTS: Infants born from mothers receiving zinc supplements during pregnancy and postpartum had significantly lower plasma zinc (p < 0.05) but marginally higher IL-7 and antibody responses to hepatitis B vaccination (p < 0.10) than infants born from mothers not receiving zinc. Maternal zinc supplementation showed no negative impact on copper status of mothers or their infants. Maternal zinc supplementation did not influence infant thymic size, but cord blood IL-7 was found positively associated with thymus size at 1 month of age (r = 0.392) and with hepatitis B vaccine response at 6 months of age (r = 0.386). CONCLUSION: Prenatal and postnatal zinc supplementation marginally improved T cell-dependent antibody responses in infants along with IL-7, a cytokine involved in human T cell development and maintaining homeostasis.

ANTIVIRAL ACTIVITY OF DIANTHUS SUPERBUSN L. AGAINST HEPATITIS B VIRUS IN VITRO AND IN VIVO.

BACKGROUND: Hepatitis is a viral infection of hepatitis B virus (HBV). Limitations of drug used in the management of it opens the interest related to alternative medicine. The given study deals with the antiviral activity of Dianthus superbusn L. (DSL) against HBV in vitro & in vivo. MATERIAL AND METHODS: In vitro study liver cell line HepG2.2.15 was used by transinfected it with HBV. Cytotoxicity stduy was performed by using different concentrations of DSL such as 50, 100, 200, 500 & 1000 µg/ml. Anti HBV activity of DSL was estimated by assesing the concentration of HBsAg and HbeAg in cell culture medium by using ELISA. Whereas in vivo study was performed on ducklings and antiviral activity of DSL (100, 200, 400 mg/kg) was confirmed by estimating the serum concentration of HBV DNA and histopathology study of hepatocytes in HBV infected ducklings. RESULT: Result of the study suggested that >500 µg/ml concentration of hydroalcoholic extract of DSL was found tobe cytotoxic. It was also observed that DSL significantly (p<0.05) reduces the concentration of antigenes in cell culture media as per the concentration and days of treatment dependent. Moreover in vivo study confirms the anti viral activity of DSL (200 & 400 mg/kg) as it significantly (p<0.05) decreases the serum concenetration of HBV DNA in HBV infected dukling compared to control group. Histopathology study was also reveals the hepatprotective effect of DSL in HBV infected ducklings. CONCLUSION: The given study concludes the antiviral activity DSL against HBV by in vitro and in vivo models.

[Effect of Negative Emotions on Serum Levels of Adrenocorticotropic Hormones and Neuropeptide Y in Hepatitis B Liver Cirrhosis Patients].

OBJECTIVE: To explore the effect of negative emotions on serum levels of adrenocorticotropic hormone (ACTH) and neuropeptide Y (NYP) in hepatitis B liver cirrhosis (HBLC) patients. METHODS: Totally 617 HBLC patients were assigned to the negative emotion group (415 cases) and the non-negative emotion group (202 cases) judged by negative emotions. Case numbers of various grading Child-Pugh were recorded in the two groups. Their liver functions were compared between the two groups. Serum levels of ACTH and NPY were detected using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in the two groups. RESULTS: There was no statistical difference in Child-Pugh grading between the two groups (χ2 = 0.65, P = 0.72). Compared with the non-negative emotional group, serum ACTH levels decreased significantly in the negative emotion group with statistical difference (P < 0.05). There was no statistical difference in serum ACTH levels between the two groups (P > 0.05). CONCLUSION: The negative emotion of HBLC patients was not related to the serum ACTH level, but to relatively lower-concentration serum NPY levels.

Correlation between Traditional Chinese Medicine symptom patterns and serum concentration of zinc, iron, copper and magnesium in patients with hepatitis B and associated liver cirrhosis.

OBJECTIVE: To investigate the correlation between the patterns of Traditional Chinese Medicine (TCM) syndromes and the serum concentration of zinc, iron, copper and magnesium of patients with chronic hepatitis B (CHB) and hepatitis B virus (HBV)-induced liver cirrhosis. METHODS: A total of 86 patients were included in the study between March 1, 2009 and January 1, 2010. All were diagnosed with CHB or HBV-induced liver cirrhosis according to the diagnosis standard of the Chinese Medical Association. Fasting serum concentrations of zinc, iron, copper and magnesium were measured. Patients were classified into different patterns of TCM symptoms according to TCM theory and clinical experience. RESULTS: In the HBV-induced liver cirrhosis group, the mean zinc concentration in patients with the TCM pattern of stagnation of fluid-Dampness was lower than that in patients with obstruction of collaterals by Blood stasis (P < 0.034). In the CHB group, the mean magnesium concentration in patients with toxic Heat flourishing was significantly lower than that in those with Damp-Heat in the Liver and Gallbladder, and those with Liver depression and Spleen deficiency (P < 0.021). The concentrations of iron and copper showed little difference among the different TCM symptom patterns. CONCLUSION: The serum zinc and magnesium concentrations correlated with certain TCM patterns of symptoms in patients with HBV-induced liver cirrhosis and CHB. It may be helpful to interpret the pathogenic change in the TCM symptom patterns in liver cirrhosis and CHB, and also to conduct clinical treatment of the diseases based on identified TCM patterns.

Study of ZHENG differentiation in hepatitis B-caused cirrhosis: a transcriptional profiling analysis.

BACKGROUND: In traditional Chinese medicine (TCM) clinical practice, ZHENG (also known as TCM syndrome) helps to understand the human homeostasis and guide individualized treatment. However, the scientific basis of ZHENG remains unclear due to limitations of current reductionist approaches. METHODS: We collected the leukocyte samples of three hepatitis B-caused cirrhosis (HBC) patients with dampness-heat accumulation syndrome (DHAS) and three HBC patients with liver depression and spleen deficiency syndrome (LDSDS) for microarray analysis. We generated Gene-Regulatory-Networks (GeneRelNet) from the differentially expressed genes (DEGs) of microarray date. Core genes were validated using anther independent cohort of 40 HBC patients (20 DHAS, 20 LDSDS) with RT-PCR. RESULTS: There were 2457 mapped genes were differentially expressed between DHAS and LDSDS (Fold change ≥ 2.0, P < 0.05). There were markedly different genes co-expression patterns in DHAS and LDSDS. Furthermore, three differential co-expression genes including purine nucleoside phosphorylase (PNP); aquaporin 7 (AQP7) and proteasome 26S subunit, non-ATPase 2 (PSMD2) were screened by GeneRelNets, and their mRNA expressions were further validated by real time RT-PCR. The results were consistent with microarray. The PNP (P = 0.007), AQP7 (P = 0.038) and PSMD2 (P = 0.009) mRNA expression is significant difference between DHAS and LDSDS using the non-parametric test. Furthermore, we constructed an mRNA panel of PNP, AQP7 and PSMD2 (PAP panel) by logistic regression model, and evaluated the PAP panel to distinguish DHAS from LDSDS by area under the receiver operating characteristic curve (AUC) analysis, which showed a higher accuracy (AUC = 0.835). Gene ontology (GO) analysis indicated that the DHAS is most likely related to system process while the functions overrepresented by LDSDS most related to the response to stimulus. CONCLUSIONS: This study suggested that there are particular transcriptional profiles, genes co-expressions patterns and functional properties of DHAS and LDSDS, and PNP, AQP7, and PSMD2 may be involved in ZHENG differentiation of DHAS and LDSDS in HBC.

[Research on HBV DNA inhibition of plasmid acute infection mouse with betulinic acid].

Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with betulinic acid. Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the betulinic acid and lamivudine groups were inhibited compared with the control group. Taken together, these results reveal betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model.

Decline in serum 25 hydroxyvitamin D levels in HIV-HBV-coinfected patients after long-term antiretroviral therapy.

BACKGROUND: Vitamin D insufficiency plays an important role in the development of fibrosis in chronic liver disease. METHODS: This was a cross-sectional study from Thailand. Liver fibrosis was assessed by transient elastography. Serum 25 hydroxyvitamin D (25[OH]D)<30 ng/ml was defined as hypovitaminosis D. 25(OH)D was assessed prior to and following tenofovir disoproxil fumarate (TDF). Factors related to 25(OH)D levels were determined by logistic regression analysis. RESULTS: A total of 158 HIV-HBV-coinfected patients (32% female, median age 43 years) were included. Overall, liver disease was mild with 13.4% having a fibrosis score (FS) of 7.1-14 kPa and 2% with a FS>14 kPa. Median (IQR) duration on TDF was 5 years (4-7). The median estimated glomerular filtration rate was 96.9 ml/min/1.73 m(2). The median (IQR) serum 25(OH)D levels prior to and following TDF were 24.8 ng/ml (21.3-30.6) and 22.8 ng/ml (18.0-27.7), respectively; P≤0.001). The proportion of patients with hypovitaminosis D significantly increased from 72.2% (95% CI 64.7, 78.6) prior to TDF to 84.2% (95% CI 77.7, 89.0) after taking TDF (P=0.01). Factors associated with hypovitaminosis D by multivariate analysis were female sex (adjusted OR 3.8, 95% CI 1.1, 13.7; P=0.038) and duration of antiretroviral therapy (ART)>5 years (OR 3.3, 95% CI 1.2, 8.8; P=0.017). Vitamin D levels were not associated with significant liver fibrosis. CONCLUSIONS: Although our HIV-HBV-coinfected patients live in the tropics, there was a high prevalence of hypovitaminosis D, especially in female patients and those receiving prolonged ART. Since HIV-HBV-coinfection requires long-term use of the HBV-active drug, TDF, which can also contribute to bone loss, routine vitamin D assessment and supplementation as necessary should be considered.

A Chinese medicine, Kuan-Sin-Yin decoction, improves liver function in hepatitis B virus carriers: a randomized, controlled study.

OBJECTIVE: To examine the effects of a Chinese medical herb complex formula, Kuan-Sin-Yin (KSY) decoction, on hepatitis B virus (HBV) carriers. METHODS: Of 86 HBV carriers, 57 who met the inclusion criteria completed this study from February 2011 to December 2011 in Taipei City Hospital, Taiwan. The participants were randomly assigned to one of two groups: the KSY group (n=29) and a control group (n=28) that received KSY diluted 16 times. The participants took one packet of decoction per day after dinner for 6 weeks. The major outcome measurements were the percentage reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the log of the HBV DNA level. The other measurements included seroconversion of hepatitis B e antigen and responses to the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) and Short-Form-12. The measurements were collected before the first treatment and 6 weeks later. RESULTS: In the KSY group, AST and ALT levels decreased significantly and the score on the physical component of WHOQOL-BREF increased significantly. However, in the control group, there was no significant change after 6 weeks of treatment. Only the KSY group had a significant percentage reduction in ALT (change, -25.2% versus -0.74% in the control group) after 6 weeks of treatment. No major adverse effects occurred after 6 weeks of treatment. CONCLUSIONS: KSY significantly improved ALT levels. The study suggests that a longer-term study testing the efficacy of KSY in a larger sample is warranted.

The possible role of selenium concentration in hepatitis B and C patients.

BACKGROUND/AIM: The compelling evidence reported that selenium is an essential trace mineral for human beings. Selenium plays a pivotal role in the restoration of immune functions. High rates of hepatitis B and C are present in Pakistan. Epidemiologic surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as viral infection. The present study was designed to evaluate the concentration of selenium in the serum of patients suffering from hepatitis B and C. PATIENTS AND METHODS: In this cross-sectional descriptive analytical study, serum selenium concentration of 150 patients suffering from hepatitis B and C, along with 26 healthy controls, was determined by atomic absorption spectrophotometer equipped with hydride generation system, model Analytic Jena (Vario III). RESULTS: The mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis C were 101.60 ± 0.55 and 77.43 ± 0.47 µ g/L, respectively, whereas the mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis B were 107.58 ± 0.44 and 137.8 ± 0.36 µg/L. Analysis of t test showed significant difference between C and B (P<0.001) patients in serum selenium concentration, when compared with the control. CONCLUSION: The obtained results indicate that serum selenium concentration of hepatitis B and C patients is less than serum selenium concentration of healthy individuals. However, serum selenium decline is relative to severity of disease. Based on findings of this study, it is proposed that selenium should be supplemented in such patients in order to optimize nutritional support and to get better treatment response.

A combined approach of vesicle formulations and microneedle arrays for transcutaneous immunization against hepatitis B virus.

In the search for an optimal approach for the transcutaneous immunization (TCI) of hepatitis B surface antigen (HBsAg), two vesicle formulations, L595 vesicles (composed of sucrose-laurate ester and octaoxyethylene-laurate ester) and sPC vesicles (composed of soybean-phosphatidylcholine and Span-80) were prepared and characterized in vitro and in vivo. HBsAg was associated to the vesicles, resulting in sPC-HBsAg vesicles (±170nm) with 79% HBsAg association and L595-HBsAg vesicles (±75nm) with only 29% HBsAg association. The vesicles induced in mice via TCI an antibody response only when the skin was pretreated with microneedles. This response was improved by the adjuvant cholera toxin. The sPC-HBsAg vesicle formulations showed to be the most immunogenic for TCI, which was related to the higher degree of HBsAg association.

Serum selenium concentration in liver cirrhotic patients suffering from hepatitis B and C in Pakistan.

High rates of hepatitis B and C are present in Pakistan. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as viral infection. In this cross-sectional descriptive analytical study, serum selenium concentration of 150 patients suffering from hepatitis B and C patients, along with 26 healthy controls, was determined by atomic absorption spectrophotometer equipped with hydride generation system. The mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis C were 101.60 ± 0.55 and 77.43 ± 0.47 µg/l, respectively, while the mean and standard deviation of serum selenium concentration observed in male and female patients with hepatitis B was 107.58 ± 0.44 and 137.8 ± 0.36 µg/l. Analysis of t test showed significant difference between hepatitis C and B (P < 0.001) patients in serum selenium concentration when compared with control.

Effect of a fermented nutraceutical on thioredoxin level and TNF-alpha signalling in cirrhotic patients.

The aim of this study is to gain further insights into the possible nutraceutical effect on redox balance via thioredoxin (Trx) modulation and on the intrinsic susceptibility of monocytes to generate an inflammatory response. The study group consisted of thirty-two patients with compensated Child A-C, HCV-related cirrhosis. The patients were supplemented for 6 months with 6g/day of a certified fermented papaya preparation (FPP). Fifteen unsupplemented, age/gender-matched healthy subjects served as controls. The patients filled in a detailed diet-life style questionnaire, and blood samples were collected to test routine biochemistry, Trx, redox status (GSH, GSSG, GSH/GSSG ratio, 4-HNE and alpha-tocopherol). Moreover, isolated monocytes were tested for ex-vivo LPS-stimulated TNF-alpha production and TNF-alpha mRNA. As compared to control, patients with liver cirrhosis showed a significantly higher serum level of Trx. A significant correlation occurred with GSH/GSSG ratio in Child B and C patients. FPP supplementation brought about a significant reduction of Trx with levels comparable to the ones of healthy controls. Ten patients Child C (31.2 percent) showed borderline low levels of alpha-tocopherol while all cirrhotic patients, as a whole, showed a significantly abnormal redox balance. Supplementation with FPP did not modify alpha-tocopherol depletion but significantly improved redox balance parameters. Patients with liver cirrhosis showed a significantly upregulated TNF-alpha production in a time-dependent manner and this effect was more pronounced in more advanced stages of the disease and showed a significant correlation with alpha-tocopherol level. Supplementation with FPP significantly, although partially, downregulated TNF-alpha production from monocytes. Taken altogether, it would appear that the typical oxidative-inflammatory biochemical milieu of these patients is mirrored by a significant TNF-alpha upregulation at a monocyte level while a targeted nutraceutical might be a potentially amenable intervention to be part of validated scheduled treatments.