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Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.
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Gastroenterologia/história , Hepatopatia Gordurosa não Alcoólica/etiologia , Guias de Prática Clínica como Assunto , Animais , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Sociedades Médicas/normasRESUMO
Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.
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Carcinoma Hepatocelular/genética , Hepatite C Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/enzimologia , Hepatite C Crônica/virologia , Humanos , Desequilíbrio de Ligação , Cirrose Hepática/diagnóstico , Cirrose Hepática/enzimologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND & AIMS: Several genome-wide association studies have shown that genetic variations in the chromosomal region containing interleukin-28B (IL28B) gene are associated with response to treatment in hepatitis C virus (HCV) infection. This study was conducted to examine the role of genetic variations in IL28B on disease progression in Saudi Arabian patients chronically infected with hepatitis B virus (HBV). METHODS: The study included 1128 subjects divided into four categories; 304 clearance subjects, 518 inactive carriers, 212 active carriers and 94 cirrhosis/HCC. RESULTS: Three single nucleotide polymorphisms (SNPs), rs12979860 (OR=1.307; 95% CI 1.046-1.634, χ2=5.57 and P=0.0183), rs12980275 (OR=0.642; CI 0.517-0.798, χ2=16.17 and P=0.0001) and rs8105790 (OR=0.746; CI 0.592-0.941, χ2=6.12 and P=0.0133), were found to be strongly associated with HBV clearance. The frequency of the G allele of rs12980275 and the C allele of rs8105790 were found to be more in clearance group than in patients and could contribute to protection against the disease. On the other hand, only rs12979860 showed significant difference in distribution when inactive group was compared to other groups (OR=1.285; CI 1.030-1.603, χ2=4.95, P=0.0261). No significant association was evident for any of the variants when active carriers were compared to cirrhosis/HCC patients. Haplotype analysis showed that a combination of A-T-T-G of rs12980275, rs8105790, rs8099917, and rs7248668, respectively, was associated with clearance of the virus (frequency=67.5% and P=0.015). CONCLUSION: genetic variations in IL28B gene region may influence the clearance of HBV infection.
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Variação Genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/genética , Interleucinas/genética , Progressão da Doença , Frequência do Gene , Genótipo , Haplótipos/genética , Humanos , Interferons , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Arábia Saudita/epidemiologiaRESUMO
ABSTRACT: Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Fatores de Risco , Antivirais/uso terapêutico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologiaRESUMO
MHC class I polypeptide-related chain A (MICA), mapping to 6p21.33, belongs to the non-classical class I family and its expression is induced by several stress factors including viral infection. A recent genome-wide association study has identified a single nucleotide polymorphism (SNP) of MICA, rs2596542 to be significantly associated with hepatitis C-induced hepatocellular carcinoma (HCC) in a Japanese population. Therefore, this study aims to investigate whether the SNP rs2596542 plays any role in hepatitis B virus (HBV) sero-clearance or in the development of complications associated with chronic HBV such as cirrhosis and/or HCC. TaqMan genotyping assay was used to identify the association of the SNP among 584 normal healthy controls and 777 HBV-infected patients. The patient group was further categorized into inactive carriers (Group I), active carriers (Group II), cirrhosis (Group III) and cirrhosis-HCC (Group IV). Variation at this SNP was found to be significantly more frequent in control subjects than in patients (OR = 0.852; 95% C.I. = 0.730-0.994; p = 0.0415). Also, the SNP was found to have a highly significant association when the inactive carriers were compared to the rest of the patients (OR = 1.308; 95% C.I. = 1.058-1.617; p = 0.0130). The TT genotype was found to occur more frequently among active HBV carriers (groups II, III and IV) when compared to inactive HBV carriers, thus suggesting that the rs2596542-T may be recessively associated with an active HBV infection. However, no significant association was observed in the case of HBV-related cirrhosis or HCC. These findings indicate that the MICA rs2596542 has a significant role in HBV infection.
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Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Antígenos de Histocompatibilidade Classe I/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/etiologia , Polimorfismo de Nucleotídeo Único/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , DNA Viral/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/patologia , Reação em Cadeia da Polimerase , Prognóstico , Arábia SauditaRESUMO
BACKGROUND: Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy. AIMS: We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients. METHODS: Treatment-naïve HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared. RESULTS: A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4±10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P=0.03). The HCV genotype did not correlate with steatosis or SVR. CONCLUSION: Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy.
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Antivirais/uso terapêutico , Fígado Gorduroso/epidemiologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Biópsia , Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Humanos , Hiperlipidemias/epidemiologia , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prevalência , Proteínas Recombinantes , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND AIMS: The Middle East (ME) has a high prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), driven by obesity and type-2 diabetes mellitus (T2DM). Studies in Saudi Arabia (KSA) and United Arab Emirates (UAE) predict an escalating impact of NAFLD/NASH, particularly advanced fibrosis due to NASH (AF-NASH), increasing cases of cirrhosis, liver cancer and death. The scale of this burden in other ME countries is unknown with no reports of NAFLD/NASH healthcare resource utilization (HCRU) or costs. We estimated the clinical and economic burden of NAFLD/NASH in KSA, UAE and Kuwait. METHODS: Markov models populated with country-specific obesity and T2DM prevalence data estimated numbers and progression of NAFLD/NASH patients from 2018 to 2030. Model inputs, assumptions and outputs were collected from literature, national statistics, and expert consensus. RESULTS: Over 13 years, the KSA model estimated cases increasing as follows: patients with fibrosis F0-3 doubled to 2.5 m, compensated and decompensated cirrhosis and hepatocellular carcinoma trebled to 212,000; liver failure or transplant patients increased four-fold to 4,086 and liver-related death escalated from < 10,000 to > 200,000. Similar trends occurred in UAE and Kuwait. Discounted lifetime costs of NASH standard-care increased totaling USD40.41 bn, 1.59 bn and 6.36 bn in KSA, UAE (Emiratis only) and Kuwait, respectively. NASH-related costs in 2019 comprised, respectively, 5.83%, 5.80% and 7.66% of national healthcare spending. CONCLUSIONS: NASH, especially AF-NASH, should be considered a higher priority in ME Public Health policy. Our analyses should inform health policy makers to mitigate the enormity of this escalating regional burden.
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Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/epidemiologia , Efeitos Psicossociais da Doença , Humanos , Kuweit/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Arábia Saudita/epidemiologia , Emirados Árabes Unidos/epidemiologiaRESUMO
BACKGROUND/AIM: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are associated with metabolic syndrome. Despite the benign nature of NAFLD, 10% of patients may develop advanced fibrosis and cirrhosis. We aimed to identify the prevalence and factors associated with NAFLD among GD patients in the Saudi population. PATIENTS AND METHODS: This is a single-center, observational cohort study that included patients seen in general surgery clinics at our institution from 2011 to 2017. All liver biopsies were taken at the same time as the cholecystectomy. Demographical and clinical data were prospectively collected from the study population. RESULTS: Of the 301 GD patients in the study, 15% had a normal body mass index (BMI), 29% were overweight, and 56% were obese. There were 143 (47.8%) patients with NAFLD, of which 125 (41.8%) showed steatosis and 18 (6%) had nonalcoholic steatohepatitis. There was a significant positive correlation between NAFLD and age (r = 0.243; P < 0.0001), and BMI (r = 0.242; P < 0.0001). Obese patients with BMI 30-40 kg/m[2] were 2.403 (P = 0.039) more likely to have NAFLD compared with normal BMI patients, and this value increased to 6.145 (P = 0.002) in patients with BMI >40 kg/m[2]. Additionally, patients with T2DM were 2.839 times (P = 0.015) more likely to have NAFLD compared with those who did not. CONCLUSIONS: The prevalence of NAFLD among GD patients is high. High BMI and diabetes are independent factors associated with NAFLD in GD patients. The results suggest that there may be a need for routine liver biopsy in selected patients during cholecystectomy.
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RATIONALE, AIMS, AND OBJECTIVES: Clinical practice guidelines (CPGs) are significant tools for evidence-based health care quality improvement. The CPG program at King Saud University was launched as a quality improvement program to fulfil the international accreditation standards. This program was a collaboration between the Research Chair for Evidence-Based Healthcare and Knowledge Translation and the Quality Management Department. This study aims to develop a fast-track method for adaptation of evidence-based CPGs and describe results of the program. METHODS: Twenty-two clinical departments participated in the program. Following a CPGs awareness week directed to all health care professionals (HCPs), 22 teams were trained to set priorities, search, screen, assess, select, and customize the best available CPGs. The teams were technically supported by the program's CPG advisors. To address the local health care context, a modified version of the ADAPTE was used where recommendations were either accepted or rejected but not changed. A strict peer-review process for clinical content and methodology was employed. RESULTS: In addition to raising awareness and building capacity, 35 CPGs were approved for implementation by March 2018. These CPGs were integrated with other existing projects such as accreditation, electronic medical records, performance management, and training and education. Preliminary implementation audits suggest a positive impact on patient outcomes. Leadership commitment was a strength, but the high turnover of the team members required frequent and extensive training for HCPs. CONCLUSION: This model for CPG adaptation represents a quick, practical, economical method with a sense of ownership by staff. Using this modified version can be replicated in other countries to assess its validity.
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Procedimentos Clínicos/normas , Prática Clínica Baseada em Evidências/métodos , Melhoria de Qualidade/organização & administração , Fortalecimento Institucional/métodos , Fortalecimento Institucional/organização & administração , Hospitais Universitários , Humanos , Guias de Prática Clínica como Assunto , Arábia Saudita , Desenvolvimento SustentávelRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.
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Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , Cirurgia Bariátrica , Biomarcadores/sangue , Biópsia , Chalconas/uso terapêutico , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapêutico , Diagnóstico por Imagem , Estilo de Vida Saudável , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Insulina/metabolismo , Fígado/patologia , Transplante de Fígado , Programas de Rastreamento , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Pioglitazona/uso terapêutico , Prevalência , Propionatos/uso terapêutico , Tiazolidinedionas/uso terapêutico , Vitamina E/uso terapêuticoRESUMO
BACKGROUND/AIMS: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. PATIENTS AND METHODS: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). RESULTS: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012). CONCLUSIONS: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.
Assuntos
Protocolos Clínicos/normas , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Fígado Gorduroso/epidemiologia , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Hiperbilirrubinemia/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/epidemiologia , Arábia Saudita/epidemiologiaRESUMO
Interleukin-37 (IL-37) has recently been recognized as a strong anti-inflammatory cytokine having anti-tumor activity against hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients. HCC is a typical inflammation-related cancer, and genetic variations within the IL-37 gene may be associated with the risk of HBV infection. Identification of the allelic patterns that genetically have a high disease risk is essential for the development of preventive diagnostics for HBV-mediated liver disease pathogenesis. In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within the IL-37 gene and disease sequelae associated with HBV infection. We genotyped ten IL-37 SNPs in 1274 patients infected with HBV and 599 healthy controls from a Saudi Arabian population. Among the selected SNPs, two SNPs (rs2723175 and rs2708973) were strongly associated with HBV infection, and six SNPs (rs2723176, rs2723175, rs2723186, rs364030, rs28947200, rs4392270) were associated with HBV clearance, comparing healthy controls and HBV infected-patients respectively. A suggestive association of rs4849133 was identified with active HBV surface antigen (HBsAg) carrier and HBV-related liver disease progression. In conclusion, our findings suggest that variations at the IL-37 gene may be useful as genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression in the Saudi Arabian population.
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Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/imunologia , Hepatite B Crônica/genética , Interleucina-1/genética , Hepatopatias/virologia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Hepatopatias/genética , Masculino , Pessoa de Meia-Idade , Arábia SauditaRESUMO
RATIONALE, AIMS, AND OBJECTIVES: Implementation of clinical practice guidelines (CPGs) has been shown to reduce variation in practice and improve health care quality and patients' safety. There is a limited experience of CPG implementation (CPGI) in the Middle East. The CPG program in our institution was launched in 2009. The Quality Management department conducted a Failure Mode and Effect Analysis (FMEA) for further improvement of CPGI. METHODS: This is a prospective study of a qualitative/quantitative design. Our FMEA included (1) process review and recording of the steps and activities of CPGI; (2) hazard analysis by recording activity-related failure modes and their effects, identification of actions required, assigned severity, occurrence, and detection scores for each failure mode and calculated the risk priority number (RPN) by using an online interactive FMEA tool; (3) planning: RPNs were prioritized, recommendations, and further planning for new interventions were identified; and (4) monitoring: after reduction or elimination of the failure mode. The calculated RPN will be compared with subsequent analysis in post-implementation phase. RESULTS: The data were scrutinized from a feedback of quality team members using a FMEA framework to enhance the implementation of 29 adapted CPGs. The identified potential common failure modes with the highest RPN (≥ 80) included awareness/training activities, accessibility of CPGs, fewer advocates from clinical champions, and CPGs auditing. Actions included (1) organizing regular awareness activities, (2) making CPGs printed and electronic copies accessible, (3) encouraging senior practitioners to get involved in CPGI, and (4) enhancing CPGs auditing as part of the quality sustainability plan. CONCLUSION: In our experience, FMEA could be a useful tool to enhance CPGI. It helped us to identify potential barriers and prepare relevant solutions.
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Fidelidade a Diretrizes/normas , Análise do Modo e do Efeito de Falhas na Assistência à Saúde/métodos , Padrões de Prática Médica/normas , Gestão de Riscos/organização & administração , Humanos , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Melhoria de Qualidade , Arábia SauditaRESUMO
Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.
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Carcinoma Hepatocelular/virologia , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Mutação de Sentido Incorreto , Adulto , Idoso , Substituição de Aminoácidos , Portador Sadio/virologia , Progressão da Doença , Feminino , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Arábia Saudita , Adulto JovemRESUMO
Hepatitis B virus (HBV) is one of the most widespread human pathogens causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). This study investigated the clinical impact of single and combinational mutations in HBx gene on the pathogenesis of HCC during progressive stages of liver disease. The patients were categorized into inactive HBV carriers, active carriers, cirrhosis and HCC groups based on disease severity. Male sex, age > 50 years, and high serum alanine aminotransferase level were associated with risk of progressive liver disease. I127T, V131I, and F132Y/I/R mutations showed a significant increasing trend associated with the disease progression to HCC. H94Y and K130M mutations were also significantly associated with severe liver disease. One double mutation (K130M+V131I) and two triple mutations (I127T+K130M+V131L and K130M+V131I+F132Y) were observed, with significant rising prevalence through progressive clinical phases of liver disease to HCC. Several single and combinational mutations in HBx correlating with severity and progressive clinical phases of HBV infection were identified. The mutational combinations may have a synergistic effect in accelerating the progression to HCC. These specific patterns of HBx mutations can be useful in predicting the clinical outcome of HBV-infected patients and may serve as early markers of high risk of developing HCC.
RESUMO
Optimal doses of Ribavirin (RBV) for hepatitis C virus (HCV) treatment are not known. To assess the safety and efficacy of PegIFNalfa-2a in combination with an adjusted (ADJ) RBV dose based on early pharmacokinetics versus a fixed standard (STD) dose of RBV in chronic HCV genotype (GT) 4-naive patients in a randomized trial. One hundred eighty-one patients were randomized. The baseline variables were similar in both arms and females were 50.3% of the patients, 76.5% had minimal-moderate fibrosis (F0-2). Sustained virologic response (SVR) was achieved in 99 (54.7%) subjects. SVR was seen in 50/90 (55.6%) of ADJ dose of RBV and 49/91 (53.9%) of STD dose subjects. Prematurely withdrawal or discontinuation of treatment prematurely in the ADJ RBV arm occurred in 11/90 patients (12.2%) compared with 6/91 subjects (6.6%) in the STD arm (P = 0.214). Similarly, virologic relapse was seen in 14/90 (15.6%) patients of the ADJ arm and 12/91 (13.2%) of the STD arm. Anemia grade 3-4 was seen in 36.7% in ADJ versus 17.6% in STD arm (P = 0.003). Occurrence of rapid virologic response and absences of F4 fibrosis predicted SVR in a univariate analysis. However, age, gender, weight, presence of diabetes, baseline alanine aminotransferase, and vitamin D levels were not significantly different in patients achieving SVR. ADJ higher doses of RBV based on its early pharmacokinetics-based RBV do not improve SVR rates in HCV GT4 treated in combination with peg-IFN alpha-2-a versus STD therapy. Patients on ADJ higher doses of RBV experienced higher rates of anemia and require more erythropoietin without increasing SVR.
Assuntos
Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Ribavirina/farmacocinética , Ribavirina/uso terapêutico , Darbepoetina alfa/administração & dosagem , Darbepoetina alfa/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The hepatitis B virus (HBV) poses a health risk to healthcare workers who are in close proximity to infected individuals. Medical students are a particularly high-risk group due to the lack of an obligatory vaccination program and a post-vaccination screening program to determine immunity status, which results in a lack of awareness of and compliance with the HBV vaccine. METHODS: This cross-sectional survey was conducted in King Khalid University Hospital (KKUH), a tertiary care academic hospital in Riyadh, Saudi Arabia, from November 2013 to March 2014. Medical students in their second to fifth years (n=444; 213 men and 231 women) completed a self-administered questionnaire regarding awareness of HBV and compliance with the HBV vaccination program in KKUH. RESULTS: Medium to low knowledge levels were present in 53.5% of the participants, and 44.3% reported that they were not compliant with the vaccination program provided by KKUH. While 93.9% received the HBV vaccine upon entry to medical school, only 59.5% received all 3 doses, citing forgetfulness and a busy schedule as common reasons for the low compliance. There was no association between the knowledge and awareness of the participants and their compliance (p=0.988). CONCLUSION: Medical students had a low level of compliance with the HBV vaccination program, regardless of their knowledge and awareness of the disease and vaccination. We recommend that programs and campaigns be developed to increase the overall awareness of this disease. We also suggest that a mandatory HBV vaccination program should be implemented to improve the compliance rate among medical students.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Adesão à Medicação , Estudantes de Medicina , Estudos Transversais , Coleta de Dados , Feminino , Vacinas contra Hepatite B/administração & dosagem , Humanos , Imunização , Masculino , Recursos Humanos em Hospital , Arábia Saudita , Inquéritos e Questionários , Centros de Atenção Terciária , Vacinação/estatística & dados numéricosRESUMO
BACKGROUND/AIM: Transient elastography is a relatively new, noninvasive method of measuring liver stiffness. This study aimed to evaluate the diagnostic accuracy of transient elastography and other noninvasive methods for the diagnosis of esophageal varices (EV) in patients with cirrhosis. METHODS: This cross-sectional study graded EV according to size in 145 consecutive patients with cirrhosis who underwent endoscopy, Fibroscan, and other noninvasive diagnostic methods. The accuracy of these diagnostic methods in diagnosing EV was evaluated on the basis of area under receiver operating characteristic (AUROC) curves. RESULTS: Elastography was successful in 123 patients. Of these, 54.5% had hepatitis C and 10.6% had hepatitis B. EV were absent in 39.8%, small EV was present in 24.4%, and large EV was present in 35.8% of patients. Fibroscan, aspartate aminotransferase-to-platelet ratio index, and international normalized ratio showed low accuracy in diagnosing EV in non-viral-related cirrhosis patients (AUROCs 0.66, 0.68, and 0.67, respectively). Fibroscan and aspartate aminotransferase-to-platelet ratio index were more accurate in measuring EV with a viral etiology (AUROCs 0.704 and 0.703, respectively). A cutoff value of 16.9 kPa was 83.8% sensitive in diagnosing EV in non-viral-cirrhotic patients, whereas a cutoff value of 19.9 kPa was 83.4% sensitive in diagnosing EV in patients with viral hepatitis. Fibroscan was moderately accurate in diagnosing grade I EV and less accurate in diagnosing grades II and III EV in all cirrhotic patients, irrespective of the underlying etiology. CONCLUSION: Fibroscan might be useful in predicting the presence of EV in patients with cirrhosis with a viral etiology. However, endoscopy remains the gold standard for EV screening.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Adulto , Idoso , Área Sob a Curva , Aspartato Aminotransferases/sangue , Estudos Transversais , Endoscopia Gastrointestinal , Feminino , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Coeficiente Internacional Normatizado , Fígado/diagnóstico por imagem , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P = 0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P = 0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae.
Assuntos
Variação Genética , Genótipo , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/genética , Interleucinas/sangue , Interleucinas/genética , Adulto , Alelos , Progressão da Doença , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferons , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Curva ROCRESUMO
AIM: To determine the clinical, epidemiological and phenotypic characteristics of ulcerative colitis (UC) in Saudi Arabia by studying the largest cohort of Arab UC patients. METHODS: Data from UC patients attending gastroenterology clinics in four tertiary care centers in three cities between September 2009 and September 2013 were entered into a validated web-based registry, inflammatory bowel disease information system (IBDIS). The IBDIS database covers numerous aspects of inflammatory bowel disease. Patient characteristics, disease phenotype and behavior, age at diagnosis, course of the disease, and extraintestinal manifestations were recorded. RESULTS: Among 394 UC patients, males comprised 51.0% and females 49.0%. According to the Montréal classification of age, the major chunk of our patients belonged to the A2 category for age of diagnosis at 17-40 years (68.4%), while 24.2% belonged to the A3 category for age of diagnosis at > 40 years. According to the same classification, a majority of patients had extensive UC (42.7%), 35.3% had left-sided colitis and 29.2% had only proctitis. Moreover, 51.3% were in remission, 16.6% had mild UC, 23.4% had moderate UC and 8.6% had severe UC. Frequent relapse occurred in 17.4% patients, infrequent relapse in 77% and 4.8% had chronic disease. A majority (85.2%) of patients was steroid responsive. With regard to extraintestinal manifestations, arthritis was present in 16.4%, osteopenia in 31.4%, osteoporosis in 17.1% and cutaneous involvement in 7.0%. CONCLUSION: The majority of UC cases were young people (17-40 years), with a male preponderance. While the disease course was found to be similar to that reported in Western countries, more similarities were found with Asian countries with regards to the extent of the disease and response to steroid therapy.