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1.
Liver Int ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426262

RESUMO

BACKGROUND & AIMS: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. METHODS: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. RESULTS: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). CONCLUSIONS: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.

3.
Am J Transplant ; 24(2S1): S19-S118, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38431360

RESUMO

The year 2022 had continued successes and challenges for the field of kidney transplantation, as the community adapted to ongoing surges of the COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 26,309, driven by continued growth in deceased donor kidney transplants (DDKTs). The total number of candidates listed for DDKT rose slightly in 2022 but remained below 2019 listing levels, with 12.4% of candidates having been waiting 5 years or longer. Following the height of the COVID-19 pandemic, pretransplant mortality in 2022 declined across age, race and ethnicity, sex, and blood type groups. Pretransplant mortality continued to vary substantially by donation service area. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 26.7% overall, with greater nonuse of biopsied kidneys (39.8%), kidneys from donors aged 55 years or older (54.7%), and kidneys with a kidney donor profile index (KDPI) of 85% or greater (71.3%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive rose to 30.2% but only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant (LDKT) persist, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 26.3% of adult kidney transplants in 2022. Five-year graft survival after LDKT compared with DDKT was 90.0% versus 81.4% for recipients aged 18-34 years and 80.8% versus 67.8% for recipients aged 65 years or older, respectively. The total number of pediatric kidney transplants performed in 2022 decreased to 705, its lowest point in the past decade; 502 (71.2%) were DDKTs and 203 (28.8%) were LDKTs. Among pediatric recipients, LDKT remains low, with continued racial disparities. The rate of DDKT among pediatric candidates has decreased by almost 25% since 2011. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates with a reported diagnosis. Most pediatric deceased donor recipients received a kidney from a donor with a KDPI of less than 35%. The rate of delayed graft function was 5.8% in 2022 and has been stable over the past decade. Long-term graft survival continues to improve, with superior outcomes for living donor transplant recipients.


Assuntos
COVID-19 , Hepatite C , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Criança , Estados Unidos/epidemiologia , Função Retardada do Enxerto , Pandemias , Doadores de Tecidos , Doadores Vivos , Sobrevivência de Enxerto , Sistema de Registros , Rim , COVID-19/epidemiologia
4.
Acta Gastroenterol Belg ; 87(1): 44-47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38431791

RESUMO

A 46-year-old woman presented at the emergency department because of acute hepatitis with jaundice. After hepatological work-up including liver biopsy, drug induced liver disease (DILI) was suspected. Patient recovered completely within a few months. One year later she presented again with jaundice due to acute hepatitis. Vaping was the only agent that could be identified as causative agent for DILI. After VAPING cessation, the hepatitis resolved completely. Calculated RUCAM score was 10, making the diagnosis of toxic hepatitis very likely. During follow-up liver tests remained normal. This is the first report of severe DILI secondary to the use of e-cigarettes. In future vaping can be included in the differential diagnosis of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Sistemas Eletrônicos de Liberação de Nicotina , Hepatite , Icterícia , Feminino , Humanos , Pessoa de Meia-Idade , Icterícia/etiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Diagnóstico Diferencial , Doença Aguda , Hepatite/complicações
5.
Heliyon ; 10(5): e26585, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434313

RESUMO

Background: Hepatitis B virus-related decompensated cirrhosis (HBV-DC) is a critical illness with a low survival rate. Timely identification of prognostic indicators is crucial for risk stratification and personalized management of patients. The present study aimed to investigate the potential of the D-dimer-to-platelet count ratio (DPR) as a prognostic indicator for HBV-DC. Methods: A retrospective review of medical records was conducted for 164 patients diagnosed with HBV-DC. Baseline clinical and laboratory characteristics were extracted for analysis. The endpoint was 30-day mortality. Disease severity was assessed by the Model for End-stage Liver Disease (MELD) score. A multivariate logistic regression model and receiver operating characteristic curve analysis (ROC) were used to evaluate the predictive value of DPR for mortality. Results: During the 30-day follow-up period, 30 (18.3%) patients died. Non-survivors exhibited significantly higher DPR values than survivors, and a high DPR had a strong association with increased mortality. Importantly, DPR was identified as an independent risk factor for mortality in HBV-DC patients after adjustments for confounding factors (Odds ratio = 1.017; 95% Confidence interval, 1.006-1.029; p = 0.003). The cut-off value of DPR as a predictor of mortality was>57.6 (sensitivity = 57%, specificity = 86%, p < 0.001). The area under ROC curve for DPR for 30-day mortality was 0.762, comparable to the MELD score (p = 0.100). Furthermore, the combined use of DPR and MELD score further increased the area under the ROC curve to 0.897. Conclusion: Elevated DPR was demonstrated to have a correlation with unfavorable outcomes in HBV-DC patients, suggesting its potential utility as an effective biomarker for assessment of prognosis in these patients.

6.
Can J Gastroenterol Hepatol ; 2024: 5573068, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434933

RESUMO

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.


Assuntos
Emigrantes e Imigrantes , Hepatite C , Masculino , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Hepacivirus , Custos de Cuidados de Saúde , Ontário/epidemiologia
7.
Front Public Health ; 12: 1137799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435299

RESUMO

Background: The HIV epidemic in Ghana is characterized as a mix of a low-level generalized epidemic with significant contributions from transmission among female sex workers (FSW) and their clients. This study seeks to identify and describe key characteristics and sexual behaviors of FSW and estimate the prevalence of HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (HBV) among FSW in Ghana. Method: A total of 7,000 FSW were recruited for the study using Time Location Sampling (TLS) approach with 5,990 (85.6%) participants completing both biological and the behavioral aspects of the study. A structured questionnaire was administered to respondents to assess several factors, such as background characteristics, sexual risk behaviors, condom usage, HIV/AIDS knowledge, opinions, and attitudes. Trained staff conducted face-to-face interviews using mobile data collection software (REDCap) after provision of specimens for HIV and STI testing. Descriptive statistics such as medians, ranges, charts, and percentages are performed and presented. Also included, are bivariate analyses to establish relationships between FSW type and other relevant characteristics of the study. Results: Among the 7,000 (100%) FSW sampled from all regions, 6,773 took part in the behavioral and 6,217 the biological. There were 783 (11.2%) respondents who took part only in the behavioral and 227 (3.2%) only in the biological. Most were young, with a median age of 26 years, majority had never been married or were widowed/divorced and a quarter had no education or had only primary education. Majority (74.8%) of FSW first sold sex at age 25 years or less with a median age of 20 years. Most (84.8%) of the FSW indicated that they entered sex work for money, either for self or family and had an average of eleven (11) sexual partners per week. More than half (55.2%) of the FSW were new entrants who had been in sex work for less than 5 years before the study. Consistent condom use with paying clients was generally unsatisfactory (71%), and was however, very low (24%) with their intimate partners or boyfriends. Only about half (54.6%) of FSW have been exposed to HIV prevention services in the last three months preceding the survey, and this varies across regions. Overall, comprehensive knowledge about HIV and AIDS was low. Only 35% of FSW had comprehensive knowledge. HIV prevalence was 4.6% and was higher among seaters (brothel-based) and older FSW who had been sex work for a longer period. The HIV prevalence from the previous bio-behavioral survey (BBS) in 2015 and 2011 were estimated to be 6.9 and 11.1%, respectively. Conclusion: Compared to the results from the previous studies, the findings give an indication that Ghana is making significant progress in reducing the burden of HIV among FSW in the country. However, risky behaviors such as low consistent condom use, low coverage of HIV services across the regions, and low comprehensive knowledge could reverse the gains made so far. Immediate actions should be taken to expand coverage of HIV services to all locations. Efforts must be made to reach out to the new entrants while also addressing strongly held myths and misconceptions about HIV.


Assuntos
Infecções por HIV , Profissionais do Sexo , Humanos , Feminino , Adulto , Adulto Jovem , Gana/epidemiologia , Comportamento Sexual , Inquéritos e Questionários , Infecções por HIV/epidemiologia
8.
Eur Rev Med Pharmacol Sci ; 28(4): 1259-1271, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436159

RESUMO

OBJECTIVE: This study aimed to assess the hepatoprotective role of oleuropein (Olp), a phenolic compound found in olive, against carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The research involved male albino rats, which received intraperitoneal injections of 100 mg/kg b.w. of oleuropein for 8 consecutive weeks before being subjected to carbon tetrachloride (CCl4) at a dosage of 1.0 ml/kg b.w. Changes induced by CCl4 in antioxidant and inflammatory marker levels were assessed using ELISA assay kits. Moreover, CCl4-induced liver tissue architecture alteration, fibrosis, and expression pattern of protein were evaluated by performing H&E, Sirius red, Masson trichrome, and immunohistochemistry staining. RESULTS: Increased serum transaminases and massive hepatic damage were observed by this liver toxicant. The hepatic injury was further evidenced by a significant decrease in antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx), Glutathione (GSH) and Total Antioxidant Capacity (T-AOC)]. The administration of CCl4 resulted in an increased inflammatory response, which was measured by C-reactive protein, interleukin-6, as well as tumor necrosis factor-alpha. Olp as a curative regimen led to significant attenuation in the inflammatory response and oxidative/nitrosative stress. This polyphenol treatment improved the hepatic tissue architecture and decreased fibrosis. In the CCl4 treatment group, the expression pattern of IL-6 protein was high, whereas expression was decreased after Olp, as evidenced by immunohistochemistry staining. CONCLUSIONS: The study suggests that oleuropein treatment has the potential to reduce liver damage caused by CCl4 induction by inhibiting oxidative stress and inflammation and maintaining liver tissue architecture. This could make it a promising treatment option for liver pathogenesis.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Glucosídeos Iridoides , Olea , Masculino , Animais , Ratos , Antioxidantes/farmacologia , Tetracloreto de Carbono/toxicidade , Inflamação/tratamento farmacológico , Estresse Oxidativo , Fenóis/farmacologia , Glutationa , Fibrose
9.
Eur Rev Med Pharmacol Sci ; 28(4): 1327-1339, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436166

RESUMO

OBJECTIVE: The occurrence of nephrotoxicity and hepatotoxicity as a result of cisplatin administration is a major concern in clinical practice. This study examined the potential protective effects of administering mesenchymal stem cells (MSCs) on the renal and hepatic damage caused by cisplatin. Moreover, the study investigated the potential protective effects of administering Adipose-Derived Mesenchymal Stem Cells (ADMSC) to counteract the harmful effects of cisplatin-induced kidney and liver damage. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into three groups: normal control, cisplatin + saline, and cisplatin + ADMSC. Cisplatin was administered to induce toxicity, and ADMSC was administered intravenously as a potential therapeutic intervention. Biochemical parameters and histopathological changes were assessed in the kidney and liver tissues. Statistical analyses were performed using a one-way ANOVA. RESULTS: Cisplatin increased malondialdehyde (MDA), tumor necrosis factor alfa (TNF-alfa), IL-6, alanine transaminase (ALT), creatinine, Galectin-3, Tissue growth factor beta 1 (TGF-beta 1), compared to the normal control group. Cisplatin-MSC reduced these levels. Histopathology showed that cisplatin caused kidney tubular epithelial necrosis, luminal necrotic debris, tubular dilatation, interstitial inflammation, liver sinusoidal and central vein dilatation, congestion, necrosis, and cytoplasmic vacuolization. ADMSC administration significantly reduced histopathological changes. CONCLUSIONS: These findings highlight the potential therapeutic benefits of mesenchymal stem cell (MSC) administration in mitigating cisplatin-induced nephrotoxicity and hepatotoxicity. MSC treatment demonstrated protective effects by reducing oxidative stress, inflammatory markers, and histopathological alterations. Further investigations are warranted to elucidate the precise mechanisms underlying these protective effects and evaluate their clinical implications for managing cisplatin-induced organ damage.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Cisplatino , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Cisplatino/toxicidade , Rim , Necrose
10.
Eur Rev Med Pharmacol Sci ; 28(4): 1632-1638, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436196

RESUMO

BACKGROUND: An increasing number of coronavirus disease 2019 (COVID-19) related autoimmune hepatitis (AIH) and autoimmune liver disease (AILD) has been already described so far in the last three years. This rise has set up some diagnostic and therapeutic concerns, although steroid therapy has mostly been efficient, avoiding main significant side effects. CASE REPORT: We report the case of a 52-year-old subject displaying liver function impairment at the laboratory tests while positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab. Needle liver biopsy showed severe portal inflammation, interface hepatitis, lobular inflammation, abundant plasma cells, bridging necrosis, endothelialitis, bile duct vanishing disease, and ductular reaction. The diagnosis of autoimmune liver disease (AILD) was performed. After a month of steroid and ursodeoxycholic acid medications, liver function fully recovered. Azathioprine was introduced, and steroids were gradually reduced. CONCLUSIONS: Probably triggered by the SARS-CoV-2-induced cytokine storm, the association between COVID-19 and autoimmune-related inflammatory injury may display a particular paradigm of AILD pathogenesis.


Assuntos
Doenças dos Ductos Biliares , COVID-19 , Hepatite Autoimune , Hepatopatias , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , COVID-19/complicações , Hepatopatias/diagnóstico , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Inflamação , Ácido Ursodesoxicólico/uso terapêutico
11.
Cureus ; 16(1): e53243, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38425592

RESUMO

Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP. Methods This was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1 January 2022 to 31 December 2022. All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1 January 2022 to 30 June 2022) and were followed for six more months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma, any other malignancy as per a history of solid organ transplant, a history of HIV infection, or those underlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve (AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained. Results The total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively. Conclusion Ascitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.

12.
J Viral Hepat ; 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433561

RESUMO

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

13.
J Med Virol ; 96(3): e29481, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38425184

RESUMO

Hepatitis C remains a global health problem, especially in poverty-stricken areas. A rapid and sensitive point-of-care (POC) diagnostic tool is critical for the early detection and timely treatment of hepatitis C virus (HCV) infection. Here, for the first time, we reported a novel molecular diagnostic assay, termed reverse transcription multiple cross displacement amplification integrated with a gold-nanoparticle-based lateral flow biosensor (RT-MCDA-AuNPs-LFB), which was developed for rapid, sensitive, specific, and visual identification of HCV. HCV-RT-MCDA induced rapid isothermal amplification through a specific primer set targeting the 5'untranslated region gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a that are prevalent in China. The optimal reaction temperature and time for RT-MCDA-AuNPs-LFB were 68°C and 25 min, respectively. The limit of detection of the assay was 10 copies per test, and the specificity was 100% for the experimental strains. The whole detection procedure, including crude nucleic acid isolation (~5 min), RT-MCDA (68°C, 25 min), and visual AuNPs-LFB result confirmation (less than 2 min), was performed within 35 min. The preliminary results indicated that the HCV-RT-MCDA-AuNPs-LFB assay could be a valuable tool for sensitive, specific, visual, cost-saving, and rapid detection of HCV and has potential as a POC diagnostic platform for field screening and early clinical detection of HCV infection.


Assuntos
Técnicas Biossensoriais , Hepatite C , Nanopartículas Metálicas , Humanos , Hepacivirus/genética , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Ouro , Hepatite C/diagnóstico , Técnicas Biossensoriais/métodos
14.
PLoS One ; 19(3): e0297617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427654

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a global public health problem against which vaccination is recommended for all high-risk adults. HBV is highly endemic in Northern Uganda, however, there is a paucity of literature regarding HBV vaccine uptake and associated factors within the community in the region. In this study, we aimed to determine the level of HBV vaccine uptake and associated factors among adults in Gulu city, Uganda. METHODS: We conducted a community-based, cross-sectional study in Gulu city among eligible adults between March and May 2022. Data on HBV vaccination status and sociodemographic characteristics were collected using an interviewer-administered questionnaire. Full uptake of HBV vaccine was defined as receipt of all 3 recommended doses, and partial uptake for 1 or 2 doses. Multivariable logistic regression analysis was performed using STATA 16.0 to determine factors independently associated with HBV vaccine uptake. P<0.05 was considered statistically significant. RESULTS: In total, 360 participants were enrolled, of whom 212 (58.9%) were female, 183 (50.8%) were aged 30 years or younger, and 143 (39.7%) had attained tertiary education. Overall, 96 (26.7%) participants had full uptake of HBV vaccine and 73 (20.3%) had partial uptake. Factors that were statistically significantly associated with full uptake of HBV vaccine were good knowledge regarding HBV transmission (aOR = 1.9, 95% Confidence Interval (CI) = 1.03-3.46, p = 0.040) and receiving health education on HBV vaccination (aOR = 4.4, 95% CI = 2.3-8.4, p<0.001). CONCLUSIONS: There is a low uptake of HBV vaccine in Gulu city, Uganda. The Uganda Ministry of Health should correct misconceptions, create awareness of the severity of HBV infection through health education regarding HBV infection within the community in Gulu City; and set mechanisms to follow-up clients due for next HBV vaccination.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Adulto , Humanos , Feminino , Masculino , Estudos Transversais , Uganda/epidemiologia , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B
15.
Rapid Commun Mass Spectrom ; 38(9): e9731, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38469943

RESUMO

RATIONALE: Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF) in North America. To investigate the effect of drug-induced liver injury (DILI) on circulating bile acid (BA) profiles, serum from ALF patients and healthy controls were analyzed using a semitargeted high-resolution mass spectrometry approach to measure BAs in their unconjugated and amidated forms and their glucuronide and sulfate conjugates. METHODS: Human serum samples from 20 healthy volunteers and 34 ALF patients were combined with deuterated BAs and extracted, prior to liquid chromatography high-resolution tandem mass spectrometry analysis. A mix of 46 standards helped assign 26 BAs in human serum by accurate mass and retention time matching. Moreover, other isomers of unconjugated and amidated BAs, as well as glucuronide and sulfate conjugates, were assigned by accurate mass filtering. In vitro incubations of standard BAs provided increased information for certain peaks of interest. RESULTS: A total of 275 BA metabolites, with confirmed or putative assignments, were measured in human serum samples. APAP overdose significantly influenced the levels of most BAs, promoting glycine conjugation, and, to a lesser extent, taurine conjugation. When patient outcome was considered, 11 BAs were altered significantly, including multiple sulfated species. Although many of the BAs measured did not have exact structures assigned, several putatively identified BAs of interest were further characterized using in vitro incubations. CONCLUSION: An optimized chromatographic separation tailored to BAs of ranging polarities was combined with accurate mass measurements to investigate the effect that DILI has on their complex profiles and metabolism to a much wider extent than previously possible. The analysis of complex BA profiles enabled in-depth analysis of the BA metabolism perturbations in ALF, including certain metabolites related to patient outcomes.


Assuntos
Ácidos e Sais Biliares , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Acetaminofen/efeitos adversos , Glucuronídeos , Espectrometria de Massas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Sulfatos , Fígado
16.
J Med Virol ; 96(3): e29515, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469923

RESUMO

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , Receptor de Morte Celular Programada 1/genética , Estudos Longitudinais , Antígenos do Núcleo do Vírus da Hepatite B , Linfócitos T CD8-Positivos
17.
Hepatol Commun ; 8(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466881

RESUMO

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1ß, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.


Assuntos
Berberina , Microbioma Gastrointestinal , Hepatite A , Hepatite Autoimune , Camundongos , Animais , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/etiologia , Berberina/farmacologia , Berberina/uso terapêutico , Concanavalina A/farmacologia , Lipopolissacarídeos/farmacologia , RNA Ribossômico 16S
18.
Hepatol Commun ; 8(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466883

RESUMO

BACKGROUND AIMS: The Revised Electronic Causality Assessment Method (RECAM), a computerized update of the Roussel Uclaf Causality Assessment Methodology (RUCAM), was recently proposed. In this study, we validated and compared the utility of the RECAM and RUCAM in Chinese patients with a single conventional or herbal agent-induced liver injury. METHODS: In this retrospective multicenter cohort of well-established DILI and non-DILI patients from 5 centers in China, the diagnostic performance of the RUCAM and RECAM was compared by AUC analysis. The consistency was evaluated by weighted kappa. The major causes of discrepancy were explored. RESULTS: A total of 481 DILI and 100 non-DILI patients were included. In total, 62.6% of the DILI cases were induced by conventional agents, and 37.4% were induced by herbs. The RECAM had relatively higher AUC than RUCAM for overall [0.947 (0.926-0.964) vs. 0.867 (0.836-0.893), p=0.0016], conventional agents [0.923 (0.890-0.949) vs. 0.819 (0.775-0.858), p=0.0185], and herbs [0.972 (0.941-0.989) vs.0.911 (0.866-0.944), p=0.0199]. Latency, scores associated with hepatitis B, and hepatotoxicity information of the insulting drugs were the 3 main causes for the inconsistency between RECAM and RUCAM scores. CONCLUSIONS: The RECAM had relatively better diagnostic performance than RUCAM, with a higher AUC for Chinese DILI patients. Timely updates of the LiverTox category and refinement of serum markers to exclude hepatitis B activity would further improve the applicability of RECAM in areas where the use of herbs and resolution of past HBV infections are common.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite B , Humanos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , China , Eletrônica
19.
Hepatology ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478755

RESUMO

BACKGROUND AIMS: Chronic hepatitis D is the most debilitating form of viral hepatitis frequently progressing to cirrhosis and subsequent decompensation. However, the HDV entry inhibitor bulevirtide is only approved for antiviral treatment of patients with compensated disease. We aimed for the analysis of real-world data on the off-label use of bulevirtide in the setting of decompensated liver cirrhosis. APPROACH RESULTS: We conducted a retrospective study in HDV-patients with decompensated liver disease at German, Austrian and Italian centers. We included 19 patients (47% male, mean age: 51 y) with liver cirrhosis Child-Pugh B. Median MELD score was 12 (range 9-17) at treatment initiation. Median observation period was 41 weeks. Virologic response was achieved in 74% and normal ALT was observed in 74%. Combined response was achieved by 42%. The most relevant adverse events included self-limited ALT flares, an asymptomatic increase in bile acids and need for liver transplantation. Despite bile acid increases adverse events were considered unrelated. Clinical and laboratory improvement from Child-Pugh B to A occurred in 47% (n=9/19). Improvements in the amount of ascites were observed in 58% of patients initially presenting with ascites (n=7/12). CONCLUSIONS: This report on off-label bulevirtide treatment in patients with decompensated HDV cirrhosis shows similar virologic and biochemical response rates as observed in compensated liver disease. Significant improvements were observed on surrogates of hepatic function and portal hypertension. However, this improvement was not seen in all patients. Controlled trials are needed to confirm safety and efficacy of bulevirtide in decompensated HDV-cirrhosis.

20.
J Hepatol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38479612

RESUMO

BACKGROUND AND AIMS: Non-invasive tests (NIT) for clinically significant portal hypertension (CSPH) in compensated advanced chronic liver disease (cACLD) lack validation in patients infected with hepatitis D virus (HDV). METHODS: HDV-cACLD patients (LSM ≥10 kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno-VII criteria and refined algorithms (Baveno-VII-VITRO, Baveno-VII-SSM) was evaluated. The prognostic utility of NIT was investigated in the main and an independent, multicenter validation cohort. RESULTS: Fifty-one patients (HVPG ≥10 mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. LSM (25.8 [17.2-31.0] vs. 14.0 [10.5-19.8] kPa; p<0.001), VITRO (n=31, 3.5 [2.7-4.5] vs. 1.3 [0.6-2.0] %/[G/L]; p<0.001), and SSM (n=20, 53.8 [41.7-75.5] vs. 24.0 [17.0-33.9] kPa; p<0.001) were significantly higher in CSPH patients. Composite CSPH risk models yielded excellent AUROC (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno-VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno-VII 'grey zone' (41.1%) was significantly reduced by Baveno-VII-VITRO or Baveno-VII-SSM, while maintaining diagnostic accuracy. Hepatic decompensation within two years occurred only in patients who had CSPH or met Baveno-VII rule-in criteria. The prognostic value of NIT was confirmed in the validation cohort comprising 92 patients. CONCLUSIONS: Standalone and composite NIT/ diagnostic algorithms are useful for CSPH diagnosis in HDV-cACLD patients. Thus, NIT may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against CHD. IMPACT AND IMPLICATIONS: Non-invasive tests (NIT) for clinically significant portal hypertension (CSPH) have been developed to identify compensated advanced chronic liver disease (cACLD) patients at risk for decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study including 51 HDV-cACLD patients, NIT, i.e., most importantly, the ANTICIPATE model based on LSM and platelet count, but also lab-based approaches, i.e., 3P/5P model and the von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) yielded high AUROC for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH-risk were at risk for decompensation within two years, and the prognostic value of NIT was confirmed in a validation cohort. Thus, NIT should be applied and updated in yearly intervals in clinical routine to identify HDV-cACLD patients at short-term risk and may guide prioritization for novel antiviral treatment options.

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