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  1. Article ; Online: Drug induced liver injury - a 2023 update.

    Allison, Rebecca / Guraka, Asha / Shawa, Isaac Thom / Tripathi, Gyan / Moritz, Wolfgang / Kermanizadeh, Ali

    Journal of toxicology and environmental health. Part B, Critical reviews

    2023  Volume 26, Issue 8, Page(s) 442–467

    Abstract: Drug-Induced Liver Injury (DILI) constitutes hepatic damage attributed to drug exposure. DILI may be categorized as hepatocellular, cholestatic or mixed and might also involve immune responses. When DILI occurs in dose-dependent manner, it is referred to ...

    Abstract Drug-Induced Liver Injury (DILI) constitutes hepatic damage attributed to drug exposure. DILI may be categorized as hepatocellular, cholestatic or mixed and might also involve immune responses. When DILI occurs in dose-dependent manner, it is referred to as intrinsic, while if the injury occurs spontaneously, it is termed as idiosyncratic. This review predominately focused on idiosyncratic liver injury. The established molecular mechanisms for DILI include (1) mitochondria dysfunction, (2) increased reactive oxygen species levels, (3) presence of elevated apoptosis and necrosis, (4) and bile duct injuries associated with immune mediated pathways. However, it should be emphasized that the underlying mechanisms responsible for DILI are still unknown. Prevention strategies are critical as incidences occur frequently, and treatment options are limited once the injury has developed. The aim of this review was to utilize retrospective cohort studies from across the globe to gain insight into epidemiological patterns. This review considers (1) what is currently known regarding the mechanisms underlying DILI, (2) discusses potential risk factors and (3) implications of the coronavirus pandemic on DILI presentation and research. Future perspectives are also considered and discussed and include potential new biomarkers, causality assessment and reporting methods.
    MeSH term(s) Humans ; Retrospective Studies ; Chemical and Drug Induced Liver Injury/epidemiology ; Chemical and Drug Induced Liver Injury/etiology ; Liver Diseases/epidemiology ; Risk Factors
    Language English
    Publishing date 2023-10-19
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415246-0
    ISSN 1521-6950 ; 1093-7404
    ISSN (online) 1521-6950
    ISSN 1093-7404
    DOI 10.1080/10937404.2023.2261848
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi.

    Stockdale, Alexander J / Silungwe, Niza M / Shawa, Isaac Thom / Kreuels, Benno / Gordon, Melita A / Geretti, Anna Maria

    BMC infectious diseases

    2021  Volume 21, Issue 1, Page(s) 487

    Abstract: Background: The World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. ...

    Abstract Background: The World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. Hepatitis B e antigen (HBeAg) status is used in the assessment of eligibility for antiviral treatment and for prevention of mother-to-child transmission (PMTCT). Accordingly, the WHO has classified HBeAg rapid diagnostic tests (RDTs) as essential medical devices.
    Methods: We assessed the performance characteristics of three commercially available HBeAg RDTs (SD Bioline, Alere, South Africa; Creative Diagnostics, USA; and Biopanda Reagents, UK) in two hepatitis B surface antigen-positive cohorts in Blantyre, Malawi: participants of a community study (n = 100) and hospitalised patients with cirrhosis or hepatocellular carcinoma (n = 94). Two investigators, blinded to the reference test result, independently assessed each assay. We used an enzyme-linked immunoassay (Monolisa HBeAg, Bio-Rad, France) as a reference test and quantified HBeAg concentration using dilutions of the WHO HBeAg standard. We related the findings to HBV DNA levels, and evaluated treatment eligibility using the TREAT-B score.
    Results: Among 194 HBsAg positive patients, median age was 37 years, 42% were femaleand 26% were HIV co-infected. HBeAg prevalence was 47/194 (24%). The three RDTs showed diagnostic sensitivity of 28% (95% CI 16-43), 53% (38-68) and 72% (57-84) and specificity of 96-100% for detection of HBeAg. Overall inter-rater agreement κ statistic was high at 0.9-1.0. Sensitivity for identifying patients at the threshold where antiviral treatment is recommended for PMTCT, with HBV DNA > 200,000 IU/ml (39/194; 20%), was 22, 49 and 54% respectively. Using the RDTs in place of the reference HBeAg assay resulted in 3/43 (9%), 5/43 (12%) and 8/43 (19%) of patients meeting the TREAT-B treatment criteria being misclassified as ineligible for treatment. A relationship between HBeAg concentration and HBeAg detection by RDT was observed. A minimum HBeAg concentration of 2.2-3.1 log
    Conclusions: Commercially available HBeAg RDTs lack sufficient sensitivity to accurately classify hepatitis B patients in Malawi. This has implications for hepatitis B public health programs in sub-Saharan Africa. Alternative diagnostic assays are recommended.
    MeSH term(s) Adult ; Antiviral Agents/therapeutic use ; Coinfection/virology ; DNA, Viral/analysis ; Diagnostic Tests, Routine/methods ; Enzyme-Linked Immunosorbent Assay/methods ; HIV Infections/complications ; Hepatitis B/complications ; Hepatitis B/diagnosis ; Hepatitis B Surface Antigens/analysis ; Hepatitis B e Antigens/blood ; Hepatitis B virus/immunology ; Hepatitis B virus/isolation & purification ; Humans ; Infectious Disease Transmission, Vertical/prevention & control ; Malawi ; Male ; Middle Aged ; Sensitivity and Specificity ; Serologic Tests
    Chemical Substances Antiviral Agents ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens
    Language English
    Publishing date 2021-05-27
    Publishing country England
    Document type Journal Article
    ISSN 1471-2334
    ISSN (online) 1471-2334
    DOI 10.1186/s12879-021-06134-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Hepatitis B virus seroprevalence among Malawian medical students: A cross-sectional study.

    Chipetah, Froid / Chirambo, Aaron / Billiat, Ednas / Shawa, Isaac Thom

    Malawi medical journal : the journal of Medical Association of Malawi

    2017  Volume 29, Issue 1, Page(s) 29–31

    Abstract: Background: Hepatitis B virus (HBV) predominantly spreads through contact with infected blood or other body fluids and causes liver disease. HBV vaccination for students at the College of Medicine, University of Malawi, is done without screening for the ...

    Abstract Background: Hepatitis B virus (HBV) predominantly spreads through contact with infected blood or other body fluids and causes liver disease. HBV vaccination for students at the College of Medicine, University of Malawi, is done without screening for the virus. It is important to assess the prevalence of HBV antigens among foundation-year students in order to consolidate evidence in support of HBV screening before vaccination. The aim of this study was to determine the seroprevalence of HBV antigens among 2013-2014 foundation-year students at the University of Malawi College of Medicine.
    Methods: A prospective cross-sectional descriptive study was conducted among 2013-2014 foundation year students at the Malawi College of Medicine. Out of the 234 foundation-year students, written consent was obtained from 89 students. Venous blood samples were collected and tested for HBV surface antigen using SD Bioline immunochromatographic rapid assays.
    Results: Out of the 62 (69.7%) male students, none tested HBV-positive, and out of 27 (30.3%) female students, none were seropositive. This suggested the absence of HBsAg among students or presence of HBsAg levels below detectable limits.
    Conclusions: This study showed levels of HBsAg below detectable limits among healthy young adults in Malawi. HBV screening for medical students should further be assessed to ensure adequate protection before they are assigned clinical duties. These findings provide enough grounds to agitate for further surveys to support the establishment of a universal HBV immunisation programme in Malawi.
    MeSH term(s) Adult ; Cross-Sectional Studies ; Female ; Hepatitis B/blood ; Hepatitis B/epidemiology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/isolation & purification ; Humans ; Malawi/epidemiology ; Male ; Prevalence ; Prospective Studies ; Seroepidemiologic Studies ; Students, Medical/statistics & numerical data ; Universities
    Chemical Substances Hepatitis B Surface Antigens
    Language English
    Publishing date 2017-05-31
    Publishing country Malawi
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2491952-4
    ISSN 1995-7270 ; 1995-7262
    ISSN (online) 1995-7270
    ISSN 1995-7262
    DOI 10.4314/mmj.v29i1.6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Lipid interactions influence hepatitis C virus susceptibility and resistance to infection.

    Shawa, Isaac Thom / Sheridan, David A / Felmlee, Daniel J / Cramp, Matthew E

    Clinical liver disease

    2017  Volume 10, Issue 1, Page(s) 17–20

    Language English
    Publishing date 2017-07-28
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2657644-2
    ISSN 2046-2484
    ISSN 2046-2484
    DOI 10.1002/cld.643
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis.

    Sheridan, David A / Shawa, Isaac Thom / Thomas, E Louise / Felmlee, Daniel J / Bridge, Simon H / Neely, Dermot / Cobbold, Jeremy F / Holmes, Elaine / Bassendine, Margaret F / Taylor-Robinson, Simon D

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 5562

    Abstract: Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) ... ...

    Abstract Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3.
    MeSH term(s) Cholesterol ; Genotype ; Hepacivirus/genetics ; Hepatitis C ; Humans ; Lipid Metabolism/genetics
    Chemical Substances Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-09588-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Queen Elizabeth Central Hastanesine Diyare ile Başvuran Çocuklarda Cryptosporidium Parvum and Isospora Belli Enfeksiyonları Prevalansı

    Kamwendo, Elizabeth / Manda, Lameck / Makanda, Mphatso / Shawa, Isaac Thom / Banda, Daniel Lawadi / Heikens, G. Tom

    Cukurova Medical Journal (Çukurova Üniversitesi Tıp Fakültesi Dergisi); Yıl: 2012 Cilt: 37 Sayı: 3

    Abstract: Purpose: Diarrhoea in children is a common problem in low resourced countries including Malawi. It is caused by many intestinal parasites including Cryptosporidium parvum and Isospora belli. Both infections are prevalent in severely immunocompromised ... ...

    Abstract Purpose: Diarrhoea in children is a common problem in low resourced countries including Malawi. It is caused by many intestinal parasites including Cryptosporidium parvum and Isospora belli. Both infections are prevalent in severely immunocompromised individuals and may cause severe life-threatening diarrhoea. The main aim of the study was to assess the prevalence of Cryptosporidium parvum and Isospora belli infections among children presenting with diarrhoea admitted to QECH - paediatrics wards and methods used for diagnosis. Some specific objectives were to determine the prevalence of Cryptosporidium parvum and Isospora belli infections among human immunodeficiency virus (HIV) seropositive and HIV seronegative children with diarrhoea, to evaluate diagnostic methods used at QECH to identify intestinal parasites and to determine diagnostic methods that can be recommended for implementation. Methods: Faecal samples were collected from all children presenting with diarrhoea upon admission or already hospitalised were recruited excluding all children without or with acute diarrhoea (less than three days). Four smears were prepared from each sample: 2 for Ziehl Neelsen staining and the other 2 for Auramine-phenol staining. The data was entered into Microsoft Excel and analysed using Epi-Info. Results: A total of 25 children with diarrhoea under the age of five years; 10 were human immunodeficiency virus -seropositive, 7 were HIV-seronegative and 8 of them their status was unknown. Cryptosporidium parvum was detected in 4 children (16%) at 4.5% and 36.1% confidence intervals and none had Isospora belli at 0.0% and 86.3% confidence intervals. Out of those 4 who had Cryptosporidium parvum, 3 children were HIV-seropositive and 1 child was HIV-seronegative at a frequency of 30% and 14.3% respectively. No infection was seen in children whose HIV-serostatus was unknown. Conclusion: Modified Ziehl Neelsen technique and auramine-phenol staining can be used to examine stool at QECH for C.parvum and I.belli identification. Although I.belli is prevalent in our environment, it has not yet been detected in children and or evolved as an endemic pathogen and so far remains as an opportunistic pathogen in adults only. There is need to repeat the study in rainy season and include gold standard method.
    Language Turkish
    Document type Article
    ISSN 0250-5150
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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