Hepatitis B virus seromarkers among HIV infected adults on ART: An unmet need for HBV screening in eastern Ethiopia.

Progression of chronic HBV to cirrhosis, end-stage liver disease (ESLD), and hepatocellular carcinoma (HCC) is more rapid in HIV positive individuals than those with HBV alone; however, the distribution of HBV seromarkers in HIV infected individuals on antiretroviral therapy (ART) is not well described. To address this problem, we assessed the distribution of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) among HIV infected adults on ART in Eastern Ethiopia. A cross-sectional study was conducted from September 2017 to February 2018. Socio-demographic, behavioral and health related factors, and clinical data were collected using questionnaire and checklist. Plasma samples were tested for HBsAg, anti-HBc and anti-HBs seromarkers using ELISA. Data were double entered into EpiData 3.1, cleaned, exported to and analyzed using STATA 13. Descriptive and logistic regression analysis were conducted and statistical significance was decided at p≤0.05. A total of 901 participants were included and the prevalence of HBsAg was found to be 11.7% [95%CI (10, 14)]. Among the co-infected, 47.6% were also positive for anti-HBc, of which 58% were on an ART containing tenofovir (TDF). Among those screened for the three seromarkers, 38.1% were negative for all and 21% were positive only for anti-HBc (IAHBc). Being single, history of genital discharge and taking ART with TDF combination were significantly associated with HBV co-infection (p≤0.05). There is high burden HBV co-infection among individuals on ART. The unmet need of HBV screening prior to ART initiation leaves many co-infected individuals without appropriate management including therapy, close monitoring or vaccination when indicated, impacting disease prevention.

Prevalence and factors associated with use of khat: a survey of patients entering HIV treatment programs in Ethiopia.

BACKGROUND: Khat, a plant native to East Africa, has psychoactive constituents similar to amphetamine. Chronic khat use can lead to psychological dependence with multiple physical and mental health harms, complicating clinical management of people living with HIV. In two Ethiopian cities where khat is common, we evaluated prevalence and correlates of khat use among patients new to HIV care. METHODS: During 2013-2014, we surveyed 322 patients recently enrolled in HIV clinics in Dire Dawa and Harar about khat use, demographics, smoking and alcohol use, clinical illness, food insecurity, and social support. We analyzed factors associated with khat use in the past year, as well as heaviest use of khat (based on greatest number of hours used in a typical month). RESULTS: 242 (75%) respondents reported lifetime khat use; 209 (65%) reported khat use during the previous year. 54% of khat users started before age 19 years. Although 84% believed that using khat every day is dangerous for health if you have HIV, khat was used in the previous year a median of 5 h/days and 30 days/month; 21% said they felt a need to cut down or control their khat use but had difficulty doing so. Those using khat were more likely to report smoking (46%) and alcohol use (49%) compared to non-khat users (1 and 31% respectively). Those reporting heaviest khat use (≥180 h/typical month) were more likely to rate their health status as poor, have an underweight BMI (≤18.5 kg/m2), report more symptoms of chronic illness, and agree with more statements indicating a negative physical quality of life. In multivariate analysis, heavy users were more likely to be male, Muslim, and non-married. CONCLUSIONS: Khat use was common among HIV patients entering care, and associated with symptoms of poorer physical health. Over half started khat use when they were young. Although most believed khat is harmful for HIV patients, a number of respondents reported some difficulty controlling their drug use. In settings where khat is legal and widely utilized, developing interventions for responsible use represent an important health priority as part of comprehensive care for people living with HIV.

Expression of MCRS1 and MCRS2 and their correlation with serum carcinoembryonic antigen in colorectal cancer.

Cancer-associated genes serve a crucial role in carcinogenesis. The present study aimed to investigate the mRNA expression levels of microspherule protein 1 (MCRS1) and MCRS2 in colorectal cancer (CRC) and their association with clinical variables. The mRNA expression levels of MCRS1 and MCRS2 were assessed by semi-quantitative reverse transcription polymerase chain reaction in the tumor and corresponding non-tumor tissues of 54 newly-diagnosed CRC patients, as well as in the normal colonic mucosa tissue of 19 age/gender-matched healthy controls. Immunofluorescence was also employed to identify the expression of MCRS1 in CRC tissues, while the concentration of serum carcinoembryonic antigen (CEA) was determined by an enzyme-linked immunoassay. The results identified a negative correlation between MCRS1 and MCRS2 expression levels (r=-0.3018, P=0.0266). MCRS1 mRNA expression was significantly increased and MCRS2 mRNA expression was decreased in CRC tissues compared with the levels in the corresponding normal tissues (both P<0.001). An increase in MCRS1 expression and a decrease in MCRS2 expression was detected in advanced stage when compared with early stage CRC patients. Immunofluorescence analysis revealed increased expression of MCRS1 in CRC patients. Furthermore, the expression levels of MCRS1 displayed positive correlation, whilst those of MCRS2 displayed negative correlation, with the serum CEA level in patients with CRC. The results suggest that increased MCRS1 and decreased MCRS2 expression appeared to be involved in the pathogenesis of CRC. The present study provides evidence suggesting that MCRS1 and MCRS2 may identify CRC patients at a risk of disease relapse, and thus, may be potential tools for monitoring disease activity and act as novel diagnostic markers in the treatment of CRC.

IL-33 Enhances Humoral Immunity Against Chronic HBV Infection Through Activating CD4(+)CXCR5(+) TFH Cells.

This study aimed to investigate the potential effect of interleukin 33 (IL-33) on humoral responses to hepatitis B virus (HBV) and the possible mechanisms underlying the action of IL-33 in regulating follicular helper T (TFH) cells. The impact of IL-33 treatment on the levels of serum HBV DNA, HBsAg, HBeAg, HBsAb, and HBeAb, as well as the frequencies of CD4(+)CXCR5(+) TFH cells in wild-type HBV transgenic (HBV-Tg) mice and in a transwell coculture of HepG2.2.15 with IL-33-treated peripheral blood mononuclear cells (PBMCs) were determined. Furthermore, the gene transcription profiles in IL-33-treated TFH cells were determined by microarrays. IL-33 treatment significantly reduced the levels of serum HBV DNA, HBsAg, and HBeAg, but increased the levels of HBsAb and HBeAb in HBV-Tg mice, accompanied by increased frequency of splenic infiltrating CD4(+)CXCR5(+) TFH cells in HBV-Tg. Similarly, coculture of HepG2.2.15 cells with IL-33-treated PBMCs reduced the levels of HBV DNA, HBsAg, and HBeAg, but increased the levels of HBsAb and HBeAb. Microarray analyses indicated that IL-33 significantly modulated the transcription of many genes involved in regulating TFH activation and differentiation. Our findings suggest that IL-33 may activate TFH cells, promoting humoral responses to HBV during the pathogenic process.

Frequency of CD4+CXCR5+ TFH cells in patients with hepatitis b virus-associated membranous nephropathy.

The frequency of different subsets of CD4(+)CXCR5(+) TFH cells and serum cytokine levels were analyzed in a total of 14 patients with newly diagnosed hepatitis B virus-associated membranous nephropathy (HBV-MN), 12 individuals with immune-tolerant HBV infection (HBV-IT) and 12 healthy controls (HC). Serum cytokine levels were measured before and 10-12 weeks after treatment. Significantly higher frequency of CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+) and CD4(+)CXCR5(+)PD-1(+) TFH cells, and higher serum levels of IL-17A, IFN-γ, IL-2, IL-10, IL-4 and IL-21 were detected in HBV-MN patients compared to the HC. The percentage of CD4(+)CXCR5(+) TFH cells and serum IL-21 level in HBV-MN patients were also higher than the HBV-IT. The percentage of CD4(+)CXCR5(+) TFH cell was negatively correlated with the value of eGFR, and the percentage of CD4(+)CXCR5(+)ICOS(+) TFH cells was positively correlated with the 24-h urinary protein concentration. Notably, the percentage of CD4(+)CXCR5(+)PD-1(+) TFH cells was positively correlated with serum IL-21 level and 24-h urinary protein concentration. Treatment with prednisone or/and immunosuppressive drugs significantly reduced the frequency of CD4(+)CXCR5(+), CD4(+)CXCR5(+)PD-1(+) TFH cells and serum IL-21 level, but increased IL-4 and IL-10 levels in the patients. CD4(+)CXCR5(+) TFH cells, especially CD4(+)CXCR5(+)PD-1(+) TFH cells may participate in the pathogenesis of HBV-MN.

Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis B.

This aim of this study was to assess the potential role of IL-33 in the pathogenic process of chronic hepatitis B (CHB). The levels of serum IL-33 and soluble ST2 (sST2) in CHB patients and healthy controls (HC) were determined using enzyme-linked-immunosorbent serologic assay, and the Th1 (IFN-γ, TNF-α, IL-2) and Th2 (IL-4, IL-6, IL-10) cytokines by cytometric bead array. It was found that the levels of serum IL-33 in CHB patients were significantly higher than that of HC at the base line, but decreased after treatment with adefovir dipivoxil for 12 weeks. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHB patients than the HC. There was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum Th1 (IFN-γ, IL-2) and Th2 (IL-6, IL-10) cytokines in CHB patients significantly increased after treatment compared to the baseline. These results suggest that IL-33 is involved in the pathogenesis of CHB and that adefovir dipivoxil therapy can attenuate the production of IL-33 in patients with CHB.