In the present paper, the deleterious effects of obesity, type 2diabetes and insulin resistance, systolic and diastolic hypertension on the rate of progression of fibrosis in non-alcoholic fatty liver disease (NAFLD) patients are illustrated using a new approach utilizing the Poisson regression to model the transition rate matrix. The observed counts in the transition counts matrix are used as response variables and the covariates are the risk factors for fatty liver. Then the estimated counts from running the Poisson regression are used to estimate the transition rates using the continuous time Markov chains (CTMC) followed by exponentiation of the estimated rate matrix to obtain the transition probability matrix at specific time points. Using a hypothetical data of 150 participants followed up every year for a total of 28 years recording their demographic characteristics and their timeline of follow up are demonstrated. The findings revealed that insulin resistance expressed by MOMA-IR 2 has the most deleterious effects among other factors for increasing the rate of forward progression of patients from state 1 to state 2 as well as from state 2 to state 3 and from state 3 to state 4. The higher the level of HOMA-IR is, the more rapid the rate of progression is.
In the present paper, the deleterious effects of obesity, type 2diabetes and insulin resistance, systolic and diastolic hypertension on the rate of progression of fibrosis in non-alcoholic fatty liver disease (NAFLD) patients are illustrated using a new approach utilizing the Poisson regression to model the transition rate matrix. The observed counts in the transition counts matrix are used as response variables and the covariates are the risk factors for fatty liver. Then the estimated counts from running the Poisson regression are used to estimate the transition rates using the continuous time Markov chains (CTMCs) followed by exponentiation of the estimated rate matrix to obtain the transition probability matrix at specific time points. A depicted, hypothetical, observational, prospective longitudinal study of 150 participants followed up every year for a total of 28 years recording their demographic characteristics and their timeline follow up are demonstrated. The findings revealed that insulin resistance expressed by MOMA-IR 2 had the most deleterious effects among other factors for increasing the rate of forward progression of patients from state 1 to state 2 as well as from state 2 to state 3 and from state 3 to state 4. The higher the level of HOMA-IR is, the more rapid the rate of progression is. This analysis helps the health policy makers and medical insurance managers to allocate the financial and human resources for investigating and treating high risk patients for NAFLD. In addition, this analysis can be used by pharmaceutical companies to conduct longitudinal studies to assess the effectiveness of the newly emerging anti-fibrotic drugs.
Introduction: Silica is used in many industries such as foundries, glass production, cement, concrete, ceramic, porcelain, pottery, bricks, sandblasting, abrasives and construction activities. Several studies have linked long term silica exposure to renal diseases, especially glomerulonephritis. Aim of Work: To study the effect of silica exposure on the renal functions among iron and steel foundry workers. Materials and Methods: Seventy workers exposed to silica in an iron and steel foundry in Helwan, Egypt, were compared to 40 non-exposed individuals as regards full medical and occupational histories, full clinical examination and laboratory investigations including measurement of serum creatinine, serum cystatin C, serum urea, urinary silica, urinary albumin and urinary α1-microglobulin. Albumin creatinine ratio (ACR) and estimated glomerular filtration rate (e-GFR) were also calculated. Results: A statistically significant higher values of urinary silica, urinary albumin, urinary α1-microglobulin, serum creatinine, serum cystatin C and ACR were detected among the exposed group compared to the control. A statistically significant lower value of e-GFR was found among the exposed group. Statistically significant positive correlations were present between duration of employment and each of urinary silica, serum cystatin C, serum creatinine, serum urea, urinary α1-microglobulin, urinary albumin and ACR levels among the exposed group. Statistically significant positive correlations were also detected between urinary silica level and each of serum cystatin C, serum creatinine, serum urea, urinary α1-microglobulin, urinary albumin and ACR among the exposed group. Whereas, the e-GFR showed statistically significant negative correlations with both duration of employment and the urinary silica level among the exposed group. Conclusion and Recommendations: Silica exposure was associated with altered kidney function tests and decreased level of the e-GFR. Pre-employment and periodic medical examinations for silica-exposed workers should include clinical examination and determination of kidney functions, e-GFR, urinary α1-microglobulin and serum .cystatin C for early detection of kidney affection
In this article, I tackle the problem of non-alcoholic fatty liver disease (NAFLD) from the statistical point of view. Using the multistate model, in the form of the continuous time Markov chains, helps the statistical analysis of the progression of the disease over time. The simplest model of the health-disease-death process is applied to the NAFLD. The model is composed of 8 pdfs and 5 rates that need to be estimated. Maximum likelihood and quasi-Newton methods are applied to estimate the transition rates among states. Exponentiation of this estimated rate matrix yields the transition probability matrix. This transition probability matrix can also be estimated from solving the forward Kolmogorov differential equations. Testing time homogeneity of this CTMC that model the disease process is also discussed by the author. This can be achieved by finding an empirical probability matrix that equates the exponentiation of the transition rate matrix, which is thoroughly investigated in the chapter. Also the embedding problem that may arise when trying to find the transition rate matrix from the transition probability matrix of the corresponding discrete time model is clarified. Testing Markovian property of the chain is also presented. Some remarks are also highlighted as regard the state probability distribution and the stationary probability distribution.
The prevalence of obesity and type 2 diabetes has reached epidemic levels that parallel the rates of the widely distributed non-alcoholic fatty liver disease (NAFLD). Nearly one billion people worldwide suffered from NAFLD. The estimated annual medical costs for NAFLD exceed €35 billion in four large European countries (the United Kingdom, France, Germany, and Italy) and $100 billion in the United States. According to the American Association for the study of liver disease, NAFLD requires the presence of hepatic steatosis in more than 5 % of hepatocytes detected by histology or imaging with little consumption of alcohol and exclusion of other causes of chronic liver diseases.The risk factors for NAFLD are age>45, males are more susceptible than females, ethnicity; the Hispanics have more prevalent rates than the whites who are more susceptible than the blacks, ingestion of high fat and high cholesterol diet, genetic backgrounds like patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene which is most prevalent in Hispanics followed by non-Hispanics whites and African Americans, and features of metabolic syndrome.The newly proposed name is metabolic associated fatty liver disease (MAFLD). This new definition requires evidence of hepatic steatosis as previously mentioned plus one of three features: obesity or overweight (BMI > 25 kg/m2 in white and > 23 kg/m2 in Asian Individuals), type 2 diabetes, or lean or normal weight with evidence of metabolic dysregulation. For the definition of metabolic dysregulation , at least two risk metabolic risk factors should be present. These factors are waist circumference ≥ 102cm for males and ≥ 88cm for females in the western countries, while for the Asian and Eastern males and female , it is ≥ 90 cm and ≥ 80 cm respectively, prediabetes, homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 ,elevated high-sensitive serum C-reactive protein(CRP) denoting inflammation, elevated blood pressure or specific drug treatment, decreased high-density lipoprotein (HDL) cholesterol levels, and increased plasma triglycerides or drug treatment. The pathogenesis of this disease process can be explained by the “two-hit theory” which is updated to the “multiple or parallel hit theory”. The first hit is initiated by liver fat content exceeding five percent of the total hepatocytes and concomitant insulin resistance. This fatty liver is more vulnerable to the second hit, inflammation, and necrosis (death of cells). This inflammation is called steatohepatitis which stimulates fibrosis. Other hits that augment this steatohepatitis are the interactions of the genetic and environmental factors and the cross-talk between different organs and tissues like the adipose tissue, the pancreas, the gut (microbiota), and the liver. Liver biopsy, although invasive and has some limitations like sampling error, hospital admission, elevated costs, and obseobserver-dependents the gold standard method for diagnosis. Rigorous control of risk factors with lifestyle modifications by reducing the caloric intake and exercises can protect the liver. The newly emerging anti-fibrotic and anti-inflammatory drugs are promising to reduce the histo-pathological picture of the disease.
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