Continuous Ketone Monitoring via Wearable Microneedle Patch Platform.

Ketone bodies (KBs), especially ß-hydroxybutyrate (BHB), have gained tremendous attention as potential biomarkers as their presence in bodily fluids is closely associated with health and wellness. While a variety of blood fingerstick test strips are available for self-testing of BHB, there are major needs for wearable devices capable of continuously tracking changing BHB concentrations. To address these needs, we present here the first demonstration of a wearable microneedle-based continuous ketone monitoring (CKM) in human interstitial fluid (ISF) and illustrate its ability to closely follow the intake of ketone drinks. To ensure highly stable and selective continuous detection of ISF BHB, the new enzymatic microneedle BHB sensor relies on a gold-coated platinum working electrode modified with a reagent layer containing toluidine blue O (TBO) redox mediator, ß-hydroxybutyrate dehydrogenase (HBD) enzyme, a nicotinamide adenine dinucleotide (NAD+) cofactor, along with carbon nanotubes (CNTs), chitosan (Chit), and a poly(vinyl chloride) (PVC) outer protective layer. The skin-worn microneedle sensing device operates with a miniaturized electrochemical analyzer connected wirelessly to a mobile electronic device for capturing, processing, and displaying the data. Cytotoxicity and skin penetration studies indicate the absence of potential harmful effects. A pilot study involving multiple human subjects evaluated continuous BHB monitoring in human ISF, against gold standard BHB meter measurements, revealing the close correlation between the two methods. Such microneedle-based CKM offers considerable promise for dynamic BHB tracking toward the management of diabetic ketoacidosis and personal nutrition and wellness.

A Microstirring Oral Pill for Improving the Glucose-Lowering Effect of Metformin.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to persistent insulin resistance, resulting in elevated blood glucose levels. Metformin is the most prescribed oral drug for lowering high blood glucose levels in T2DM patients. However, it is poorly absorbed and has low bioavailability. Here, we introduce magnesium-based microstirrers to a metformin-containing pill matrix to enhance the glucose-lowering effect of metformin. The resulting microstirring pill possesses a built-in mixing capability by creating local fluid transport upon interacting with biological fluid to enable fast pill disintegration and drug release along with accelerated metformin delivery. In vivo glucose tolerance testing using a murine model demonstrates that the metformin microstirring pill significantly improves therapeutic efficacy, lowering blood glucose levels after a meal more rapidly compared to a regular metformin pill without active stirring. As a result, the microstirrers allow for dose sparing, providing effective therapeutic efficacy at a lower drug dosage than passive metformin pills. These encouraging results highlight the versatility of this simple yet elegant microstirring pill technology, which enhances drug absorption after gastrointestinal delivery to improve therapeutic efficacy.

Role of Serum Amyloid A as a Biomarker for Predicting the Severity and Prognosis of COVID-19.

Objective: To detect biomarkers that can be used to predict COVID-19 severity to identify patients with high probability of disease progression and poor prognosis. Methods: Of the 102 patients with confirmed COVID-19 who were admitted to King Fahd General Hospital, Jeddah City, Saudi Arabia, from July 1, 2021 to August 5, 2021, 50 were included in this cross-sectional study to investigate the influence of serum amyloid A (SAA) on disease severity and survival outcomes of COVID-19 patients. Dynamic shifts in SAA, C-reactive protein (CRP), white blood cell (WBC), lymphocytes, neutrophils, biochemical markers, and disease progression were examined. At admission, and at three, five, and seven days after treatment, at least four data samples were collected from all patients, and they underwent clinical status assessments. Results: Critically ill patients showed higher SAA and CRP levels and WBC and neutrophil counts and significantly lower lymphocyte and eosinophil counts compared to the moderately/severely ill patients, especially with regard to disease progression. Similarly, nonsurvivors had higher SAA levels than survivors. The moderately/severely ill patients and the survivors had significantly higher dynamic changes in SAA compared to the critically ill patients and nonsurvivors, respectively, with differences clearly noticed on the fifth and seventh day of treatment. ROC curve analysis revealed that the combination of SAA and CRP was valuable in evaluating the disease progression and prognosis of COVID-19 patients at different time points; however, a combination of SAA and lymphocyte counts was more sensitive for disease severity prediction on admission. The most sensitive parameters for predicting survival on admission were the combination of SAA/WBC and SAA/neutrophil count. Conclusions: The study findings indicate that SAA can be used as a sensitive indicator to assess the degree of disease severity and survival outcomes of COVID-19 patients.

Gastrointestinal tract drug delivery using algae motors embedded in a degradable capsule.

The use of micromotors for active drug delivery via oral administration has recently gained considerable interest. However, efficient motor-assisted delivery into the gastrointestinal (GI) tract remains challenging, owing to the short propulsion lifetime of currently used micromotor platforms. Here, we report on an efficient algae-based motor platform, which takes advantage of the fast and long-lasting swimming behavior of natural microalgae in intestinal fluid to prolong local retention within the GI tract. Fluorescent dye or cell membrane-coated nanoparticle functionalized algae motors were further embedded inside a pH-sensitive capsule to enhance delivery to the small intestines. In vitro, the algae motors displayed a constant motion behavior in simulated intestinal fluid after 12 hours of continuous operation. When orally administered in vivo into mice, the algae motors substantially improved GI distribution of the dye payload compared with traditional magnesium-based micromotors, which are limited by short propulsion lifetimes, and they also enhanced retention of a model chemotherapeutic payload in the GI tract compared with a passive nanoparticle formulation. Overall, combining the efficient motion and extended lifetime of natural algae-based motors with the protective capabilities of oral capsules results in a promising micromotor platform capable of achieving greatly improved cargo delivery in GI tissue for practical biomedical applications.

Clinical features, laboratory characteristics and risk factors for mortality of COVID-19 patients in a secondary hospital in Oman during the first wave of the SARS-CoV-2 pandemic.

Background: The changing epidemiological profile of the COVID-19 pandemic and the uncertain clinical picture of patients characterise this ongoing and most challenging health event. Objectives: To report clinical features, laboratory characteristics, and mortality risk factors among COVID-19 patients admitted to a secondary hospital in Oman. Methods: A retrospective study for the first 455 patients admitted with COVID-19 to Rustaq hospital from 12th April, 2020 to 27th September, 2020. A predesigned questionnaire collected data from the hospital medical electronic system. Results: The mean age was 42.84 (SD = 19.86) years, and the majority of patients were aged 30 to 59 and 60 or above; 207 (45.5%) and 189 (41.5%), respectively. Male patients constituted approximately two-thirds of the subjects. Fever, dyspnea and cough were the most common presenting symptoms (69%, 66%, and 62%, respectively), while comorbidities with diabetes mellitus and hypertension were 47% and 44%, respectively. Bacterial growth was identified at approximately 10%. Bivariate analysis turned out to be significant with a number of factors. However, multivariate analysis showed significance with patients aged over 60 (OR = 7.15, 95% CI 1.99-25.63), dyspnea (OR = 2.83, 95% CI 1.5-5.33), dyslipidemia (OR = 1.93, 95% CI 1.02-3.66) and being bed-ridden (OR = 5.01, 95% CI 1.73-14.44). Durations from onset of symptoms to admission and respiratory distress were lower among patients who died; p = 0.024 and p = 0.001, respectively. Urea, Troponin and LDH may act as potential diagnostic biomarkers for severity or mortality. Conclusions: This study identified groups of patients with a higher risk of mortality, with severe disturbance in the laboratory markers while some could act as potential diagnostic biomarkers.

Zinc Microrocket Pills: Fabrication and Characterization toward Active Oral Delivery.

Here the fabrication of a zinc (Zn) microrocket pill is reported, and its unique features toward active and enhanced oral delivery application are demonstrated. By loading Zn-based tubular microrockets into an orally administrable pill formulation, the resulting Zn microrocket pill can rapidly dissolve in the stomach, releasing numerous encapsulated Zn microrockets that are instantaneously activated and then propel in the gastric fluid. The released Zn microrockets display efficient propulsion without being affected by the presence of the inactive excipient materials of the pill. An in vivo retention study performed in mice clearly shows that the active pill dissolution and powerful acid-driven Zn microrocket propulsion greatly enhance the microrocket retention within the gastric tissue without causing toxic effects. By combining the active delivery feature of Zn microrockets with the oral administration of a pill, the Zn microrocket pill holds considerable potential for active oral delivery of various therapeutics for diverse medical applications.

Mechanosensing by the Lamina Protects against Nuclear Rupture, DNA Damage, and Cell-Cycle Arrest.

Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (∼1 h) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. The findings are especially relevant to organs such as the heart because DNA damage permanently arrests cardiomyocyte proliferation shortly after birth and thereby eliminates regeneration after injury including heart attack. Embryonic hearts, cardiac-differentiated iPS cells (induced pluripotent stem cells), and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell-cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and also by contractility modulators in clinical trials. Contractile cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility are seen to minimize DNA damage. Lamin-A is thus stress stabilized to mechano-protect the genome.

Characterization of embryonic cells obtained from multifetal reduction.

The multifetal reduction (MFR) procedure is usually reserved for high-order multiple pregnancies, and aspirated tissues are typically discarded. In this study, cells obtained from MFR tissue (termed multifetal reduction embryonic cells (MFR-ECs)), were characterized in vitro by genotypic and phenotypic analyses and tested in vivo by injection under the kidney capsule of nude mice. MFR-ECs were highly proliferative in culture and showed a normal karyotype by microarray CGH. Immunohistochemical analysis at day zero showed positive focal staining for desmin, S-100 protein, synaptophysin and chromogranin. Histology examination showed a mixture of cells from the three germ layers at different stages of differentiation. Markers of these stages included important developmental transcription factors, such as beta three-tubulin (ectoderm), paired box 6 (ectoderm) and alpha-smooth muscle actin (mesoderm). Quantitative polymerase chain reaction (qPCR) showed down-regulation of the mRNAs of cancer-related genes such as TP53. In vivo transplantation in nude mice showed a typical hyaline cartilage plate and no teratoma formation. Thus, MFR-ECs represent a rich, unique source for studying stem cell development, embryogenesis and cell differentiation.

Progerin phosphorylation in interphase is lower and less mechanosensitive than lamin-A,C in iPS-derived mesenchymal stem cells.

Interphase phosphorylation of lamin-A,C depends dynamically on a cell's microenvironment, including the stiffness of extracellular matrix. However, phosphorylation dynamics is poorly understood for diseased forms such as progerin, a permanently farnesylated mutant of LMNA that accelerates aging of stiff and mechanically stressed tissues. Here, fine-excision alignment mass spectrometry (FEA-MS) is developed to quantify progerin and its phosphorylation levels in patient iPS cells differentiated to mesenchymal stem cells (MSCs). The stoichiometry of total A-type lamins (including progerin) versus B-type lamins measured for Progeria iPS-MSCs prove similar to that of normal MSCs, with total A-type lamins more abundant than B-type lamins. However, progerin behaves more like farnesylated B-type lamins in mechanically-induced segregation from nuclear blebs. Phosphorylation of progerin at multiple sites in iPS-MSCs cultured on rigid plastic is also lower than that of normal lamin-A and C. Reduction of nuclear tension upon i) cell rounding/detachment from plastic, ii) culture on soft gels, and iii) inhibition of actomyosin stress increases phosphorylation and degradation of lamin-C > lamin-A > progerin. Such mechano-sensitivity diminishes, however, with passage as progerin and DNA damage accumulate. Lastly, transcription-regulating retinoids exert equal effects on both diseased and normal A-type lamins, suggesting a differential mechano-responsiveness might best explain the stiff tissue defects in Progeria.

From local to global: a qualitative review of the multi-leveled impact of a multi-country health research capacity development partnership on maternal health in Sudan.

BACKGROUND: There is a substantial body of literature on the principles of good partnerships and the rationale for such partnerships in research capacity strengthening. This paper illustrates the long term effects of a multi-country (8 countries) global partnership for health systems research capacity development (Connecting health Research in Africa and Ireland Consortium - ChRAIC) in relation to its contribution to capacity strengthening, public advocacy and policy influence at different levels and its practical achievements in Sudan in addressing access to maternal health services. METHODS: The authors (all members of the global partnership) reflect on the project in one of its' partner countries, Sudan, over its' five year duration. This reflection is supported by specific project data collected over the period of the project (2008-2014). The data collected included: (i) 6 monthly and annual donor reports; (ii) a mid-term internal and end of project independent evaluation of the entire project, and; (ii) a Ph.D study conducted by a member of the Sudanese research team. RESULTS: The ChRAIC project in Sudan achieved the deliverables set out at the beginning of the project. These included a national knowledge synthesis report on Sudan's health system; identification of country level health systems research priorities; research capacity assessment and skills training, and; the training and graduation of a Sudanese team member with a Ph.D. Mechanisms established in Sudan to facilitate these achievements included the adoption of culturally sensitive and locally specific research and capacity strengthening methods at district level; the signing of a Memorandum of Understanding at country level between the Ministry of Health, research and academic institutions in Sudan, and; the establishment of country level initiatives and a research unit. The latter being recognized globally through awards and membership in global health forums. CONCLUSION: We surmise that the 'network of action' approach adopted to partnership formation facilitated the benefits gained, but that adopting such an approach is not sufficient. More local and contextual factors influenced the extent of the benefits and the sustainability of the network.

The Interplay between Zinc, Vitamin D and, IL-17 in Patients with Chronic Hepatitis C Liver Disease.

OBJECTIVES: To assess zinc (Zn) and vitamin D (Vit. D) status in chronic Hepatitis C virus- (HCV) infected patients and their relationship to interleukin- (IL-) 17 and disease severity and then investigate whether Zn and Vit. D3 modulate IL-17 expression in chronic HCV patients. METHODS: Seventy patients and fifty healthy subjects were investigated. Serum levels of Zn, Vit. D, and IL-17 were assessed in the patients group and subgroups. Patients lymphocytes were activated in vitro in the presence or absence of Zn or Vit. D3 and then intracellular IL-17 production was assessed using flow cytometry. RESULTS: Zn and Vit. D were significantly decreased in HCV patients. Increasing disease severity leads to more reduction in Zn level opposed by increasing IL-17 level. Zn potently reduced IL-17 production in a dose-related fashion; however it did not exert any toxic effects. Although Vit. D apparently increases IL17 expression, it is unclear whether it is due to its toxic effect on cell count or lack of definite association between Vit. D and both IL-17 and disease severity. CONCLUSIONS: This study demonstrates that Zn modulates IL-17 expression and provides a rationale for evaluating this compound as a supplementary agent in the treatment of chronic HCV.

Lipid profile and hepatic steatosis in hepatitis C infected egyptian survivors of childhood cancer.

BACKGOUND/AIM: Studies associating chronic hepatitis C virus (HCV) infection with lipid profile and hepatic steatosis in children and adolescents are scarce. This study investigated lipid profile abnormalities and hepatic steatosis among HCV-infected Egyptian children and adolescents who survived leukemia and lymphoma and evaluated impact on response to antiviral therapy. SUBJECTS AND METHODS: Thirty-six leukemia/lymphoma cured children and adolescents (mean age: 12.47 ± 3.56 years) with chronic HCV infection and 30 healthy controls (mean age: 11.64 ± 3.96 years) were enrolled in this prospective study. Serum lipid profile and abdominal ultrasonography were done for all patients and controls. Guided liver biopsy with histopathological examination was done for 32 (88.9%) patients eligible for antiviral therapy. RESULTS: Total cholesterol, LDL-cholesterol, and apolipoprotein B (apo-B) in patients were significantly lower than in the control group (P ≤ .01, ≤ .01, and ≤ .05, respectively). Among those who underwent liver biopsy (n = 32), macrovesicular hepatic steatosis associated with chronic hepatitis C was documented in 10 children (31.3%). Body mass index was significantly higher (P ≤ .05) and apo-B was significantly lower in steatotic (P ≤ .05) than non-steatotic HCV-infected children. Liver span by ultrasound, alanine aminotransferase (ALT), and apo-B were independent predictors for hepatic steatosis (P < .001, <.001, and <.05, respectively). A significantly worse response to interferon alpha 2-b plus ribavrin treatment for HCV was reported among children with steatosis (P < .001). CONCLUSIONS: The study showed low serum lipids in HCV-infected children with cured leukemia/lymphoma. Hepatic steatosis was found in a significant proportion of patients and was associated with a poor response to antiviral treatment.

The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis.

UNLABELLED: Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. CONCLUSIONS: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance.

A novel association between cytotoxin-associated gene A (CagA) positive strain of Helicobacter pylori and unexplained recurrent early pregnancy loss.

OBJECTIVE: To assess whether or not there is an association between the cytotoxin-associated gene A (CagA)-positive strain of Helicobacter (H.) pylori and unexplained recurrent early pregnancy loss (REPL). METHODS: A case control study was conducted in a tertiary care maternity centre during a one-year period. Ninety-six women with first trimester unexplained REPL admitted for surgical or medical termination of pregnancy were included in the study group (group 1), along with 96 women who suffered a first trimester missed abortion but had no history of REPL and who were included in the control group (group 2). Sera from all these women were collected for detection of the CagA line of IgG type of H. pylori using an immunoblotting assay. The main outcome measure was the association between the CagA-positive strain of H. pylori and unexplained REPL. RESULTS: A significantly greater proportion of women were seropositive for the CagA- H. pylori strain in group 1 than in group 2 (71 [74%] vs. 51 [53%], respectively; p = 0.003). CONCLUSION: The CagA-positive strain of H. pylori seems to be significantly more prevalent among women with unexplained REPL when compared to women with a single missed abortion.

Sexual Transmission of HCV in Heterologous Monogamous Spouses.

We screened for evidence of HCV infection in healthy heterologous monogamous spouses of chronic HCV patients and studied the relation with various risk factors. A cross-sectional study of fifty healthy monogamous heterosexual spouses of HCV-positive index cases was carried out. All participants were HBV and HIV negative. The association with various risk factors was studied. Five spouses (10%) showed evidence of HCV infection. Two partners were positive for HCV antibody alone (4%) and 3 for antibody and HCV PCR (6%). No association was found between HCV infection and various sociodemographic parameters with the exception of older age categories. Intraspousal transmission of HCV may be an important source of spread of HCV infection. The reservoir of HCV-infected individuals in Egypt is sizable, and sexual transmission of HCV may contribute to the total burden of infection in Egypt.

Serum dickkopf-1 level in postmenopausal females: correlation with bone mineral density and serum biochemical markers.

Objective. To assess serum level of Dickkopf-1 in postmenopausal females and its correlation with bone mineral density and serum biochemical markers. Methods. Bone densitometry, serum Dickkopf-1, calcium, phosphorus, and alkaline phosphatase were done in sixty postmenopausal females. Patients were divided according to T score into osteoporosis (group I), osteopenia (group II), and normal bone mineral density that served as controls. Results. There was highly significant increase in serum Dickkopf-1 levels in postmenopausal females with abnormal T score versus controls (P < 0.001). Serum DKK-1 levels correlated negatively with both lumbar T score (r = -0.69, P < 0.001) and femur T score (r = -0.64, P < 0.001) and correlated positively with duration of menopause (r = 0.61, P < 0.001), while there was no significant correlation between serum levels of either calcium, phosphorus or alkaline phosphatase, and both serum Dickkopf-1 levels and the level of bone mineral density (P > 0.05). Conclusion. Postmenopausal females may suffer from osteoporosis as evidenced by bone densitometry. Postmenopausal women with significantly increased serum Dickkopf-1 had more significant osteoporosis. Prolonged duration of menopause and increased serum Dickkopf-1 are important risk factors for the development and severity of osteoporosis.

TH1 cytokine response to HCV peptides in Egyptian health care workers: a pilot study.

Our objective was to elucidate the effects of different HCV peptides on TH1 cytokine synthesis (interleukin 2(IL2), gamma interferon (INFγ) and tumor necrosis factor α (TNF α)), in a proliferative response in a high risk population of HCV seronegative aviremic Egyptian healthcare workers (HCW). We studied the TH1 cytokine response to different HCV peptides among 47 HCW with and without evidence of HCV infection. Participants were classified according to the proliferation index (PI) in a CFSE proliferation assay as an indicator of previous exposure to HCV. Cytokines were analyzed using Luminex xMAP technology. Results showed that positive PI HCW produced a higher IL2 in response to all HCV peptides except NS4, a higher IFNγ response to NS3 and NS4 and no difference in TNFα response when compared to the negative PI HCWs. When compared to chronic HCV HCW, positive PI HCW showed no difference in the IL2 response, a higher IFNγ response to NS4 and NS5 HCV peptides and a higher TNFα response to all peptides. In conclusion the magnitude and type of cytokines produced in HCV infection is critical in determining the outcome of infection. NS4 & NS5 HCV peptides induce a protective TH1 response in positive PI HCW.

Fibroblast growth factor 23 contributes to diminished bone mineral density in childhood inflammatory bowel disease.

BACKGROUND: Diminished bone mineral density (BMD) is of significant concern in pediatric inflammatory bowel disease (IBD). Exact etiology is debatable. The recognition of fibroblast growth factor 23 (FGF23), a phosphaturic hormone related to tumor necrosis factor alpha (TNF-α) makes it plausible to hypothesize its possible relation to this pathology. METHODS: In this follow up case control study, BMD as well as serum levels of FGF23, calcium, phosphorus, alkaline phosphatase, creatinine, parathyroid hormone, 25 hydroxy vitamin D3 and 1, 25 dihydroxy vitamin D3 were measured in 47 children with IBD during flare and reassessed in the next remission. RESULTS: Low BMD was frequent during IBD flare (87.2%) with significant improvement after remission (44.7%). During disease flare, only 21.3% of patients had vitamin D deficiency, which was severe in 12.8%. During remission, all patients had normal vitamin D except for two patients with Crohn's disease (CD) who remained vitamin D deficient. Mean value of serum FGF23 was significantly higher among patients with IBD during flare compared to controls. It showed significant improvement during remission but not to the control values. 1, 25 dihydroxy vitamin D3, FGF23, serum calcium and urinary phosphorus were significant determinants of BMD in IBD patients. CONCLUSIONS: We can conclude that diminished BMD in childhood IBD is a common multifactorial problem. Elevated FGF23 would be a novel addition to the list of factors affecting bone mineral density in this context. Further molecular studies are warranted to display the exact interplay of these factors.

HLA-DRB1 as a risk factor in children with autoimmune hepatitis and its relation to hepatitis A infection.

BACKGROUND: The human leukocyte antigens (HLAs) are proteins found in the membranes of nearly all nucleated cells. People with certain HLA antigens are more likely to develop certain autoimmune diseases. The aim of this study was to determine the frequency of HLA-DRB1 in children with autoimmune hepatitis (AIH) as a risk factor for occurrence, its relation to preceding hepatitis A infection and treatment outcome. SUBJECTS AND METHODS: 25 children with AIH were subjected to HLA-DRB 1 typing performed by sequence specific oligonucleotide probe technique and compared to HLA-DRB1 found in 548 normal populations. RESULTS: The most frequent alleles found in our children with AIH were HLA-DRB1*13 (36%), HLA-DRB1*04 (18%) and HLA-DRB1*03 (14%). HLA-DRB1*13 was significantly more frequent in AIH patients compared to controls. In type I AIH patients HLA-DRB1*13 was the most frequent allele (32.4%), followed by HLA-DRB1*04 in (20.6%) and HLA-DRB1*03 in (14.7%), While in type II, the most frequent alleles were HLA-DRB1*13 in (40%), HLA-DRB1*07 (20%) and HLA-DRB1*15 in (20%). HLA-DRB1*12 was significantly more frequent in AIH patients with positive Hepatitis A IgM than in patients with negative hepatitis A IgM. No statistically significant difference between partial responders and complete responders to treatment as regards HLA-DRB1 subtypes. CONCLUSION: It is concluded from the previous study that HLA-DRB1*13 may be a susceptibility allele for the occurrence of autoimmune hepatitis in our population. HLA-DRB1*07 and HLA-DRB1*15 may be susceptibility alleles for occurrence of autoimmune hepatitis type 2. HLA-DRB1*12 association with AIH in patients triggered by hepatitis A needs further studies.

Subclinical autoimmune thyroid disorders in Egyptian patients with untreated chronic hepatitis C virus infection.

The frequency of anti-thyroid antibodies and subclinical thyroid disorders in Egyptian patients with untreated chronic hepatitis type C was estimated. In addition, it determines the correlation between the seropositivity of anti-thyroid antibodies and serum thyroid stimulating hormone level in chronic HCV positive patients. Also, the impact of hepatic decompensation in inducing thyroid autoimmunity in such patients was evaluated. This study included 56 untreated chronic hepatitis C patients and 28 healthy subjects of the same local population as a control group. The results showed that the mean thyroid stimulating hormone levels were significantly higher in patients with chronic hepatitis C than in controls. Patients with decompensated chronic hepatitis C had insignificantly higher subsequent autoimmune hypothyroidism than the compensated patients. A significant positive correlation between the level of thyroid stimulating hormone and anti-thyroglobulin, but not with anti-thyroperoxidase, was found. Therefore, there is an association between chronic hepatitis C virus infection and subclinical autoimmune thyroid disorders. Thyroid stimulating hormone and anti-thyroglobulin antibodies screening for all chronic HCV patients, even if antiviral treatment will not be initiated, should be done.