Pritchardstevens8891
The goal of this analysis was to evaluate the association between county-level ambient vinyl chloride (VC) and county-level liver cancer incidence and mortality rates in Texas. Modeled county-level ambient VC data were obtained from the National Air Toxics Assessment. Age-adjusted county-level liver cancer incidence rates were abstracted from the Texas Cancer Registry and age-standardized county-level liver cancer mortality rates were obtained from the peer-reviewed literature. Multivariable imputation was utilized to impute incidence rates in counties with suppressed liver cancer incidence rates. Negative binomial and Poisson regression models were utilized to evaluate the association between county-level ambient VC and county-level liver cancer incidence and mortality rates, respectively, adjusted for county-level heavy drinking prevalence, hepatitis mortality rates, median income, and race (percent Hispanic). County-level ambient VC was not associated with county-level liver cancer incidence or mortality rates. Specifically, when compared to the lowest tertile of ambient VC, the middle (relative risk [RR] 1.06, 95% confidence interval [CI] 0.95-1.19) and highest (RR 1.03, 95% CI 0.90-1.17) tertiles of ambient VC were not associated with liver cancer incidence. Similarly, county-level ambient VC in the middle (RR 0.95, 95% CI 0.85-1.05) and highest (RR 0.93, 95% CI 0.82-1.05) tertiles were not associated with liver cancer mortality. This analysis suggests that county-level ambient VC is not associated with liver cancer incidence or mortality in Texas. Our study provides novel results regarding liver cancer risk from low-level non-occupational exposure to ambient VC.Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of alcohol metabolism and it is involved in the cellular mechanism of alcohol liver disease. ALDH2 gene mutations exist in about 8% of the world's population, with the incidence reaching 45% in East Asia. The mutations will result in impairment of enzyme activity and accumulation of acetaldehyde, facilitating the progression of other liver diseases, including non-alcoholic fatty liver diseases, viral hepatitis and hepatocellular carcinoma, through adduct formation and inflammatory responses. In this review, we seek to summarize recent research progress on the correlation between ALDH2 gene polymorphism and multiple liver diseases, with an attempt to provide clues for better understanding of the disease mechanism and for strategy making.The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling. It is involved in regulating multiple important biological processes, including inflammation and host immune response. A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. Currently, many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases, including cancers, autoimmune diseases, and virus infection. Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases, targeting this pathway may be a promising therapeutic strategy to alleviate liver inflammation. Moreover, activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus infection. Here, we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases, and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.Globally, the rise in prevalence of obesity and metabolic syndrome as a whole has been linked to increased access to processed foods, such as refined sugars and saturated fats. Consequently, nonalcoholic fatty liver disease (NAFLD) is on the rise in both developed and developing nations. However, much is still unknown on the NAFLD phenotype with regards to the effect of ethnic diversity. Despite similarities in dietary habits, it appears that certain ethnicities are more protected against NAFLD than others. However, manifestations of the same genetic polymorphisms in different groups of people increase those individuals' predisposition to NAFLD. 3M-052 Diets from different regions have been associated with a lower prevalence of NAFLD and have even been linked to regression of hepatic steatosis. Socioeconomic variations amongst different regions of the world also contribute to NAFLD prevalence and associated complications. Thus, a thorough understanding of ethnic variability in NAFLD is essential to tailoring treatment recommendations to patients of different backgrounds.Liver fibrosis represents a response to chronic liver injury. Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases, both with increasing incidence. Therefore, there is a great impetus for development of agents targeting these conditions. Accumulating data on possible treatment options for liver fibrosis are emerging in the literature. However, despite extensive research and much effort in the field, approved agents for liver fibrosis are still lacking. In this critical review, we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials, with an emphasis on efficacy and safety of these agents.Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and other end-stage liver disease complications. When addressing treatment of NASH, we have limited approved options, and the mainstay of therapy is lifestyle intervention. Extensive research and revelation in the field of pathogenesis of NASH has offered new possibilities of treatment and emerging new drugs that are being tested currently in numerous preclinical and clinical trials. These drugs target almost all steps in the pathogenesis of NASH to improve insulin sensitivity, glucose and lipid metabolism, to inhibit de novo lipogenesis and delivery of lipids to the liver, and to influence apoptosis, inflammation and fibrogenesis. Although NASH is a multifactorial disease, in the future we could identify the predominating pathological mechanism and, by choosing the most appropriate specific medication, tailor the treatment for every patient individually.Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH; moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or 'Holy Grail' within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.
Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population. The aim of this study was to assess the incidence of infections in cirrhotic patients in a large academic liver center and investigate potential associations between infections, bacteria isolated, therapeutic regimens used, and mortality.
This was a retrospective chart review study, including 192 patients. All patients had a diagnosis of cirrhosis and were admitted to University Hospital. Information collected included demographics, etiology of cirrhosis, identification of bacteria from cultures, multidrug-resistant (MDR) status, antibiotics administered, intensive care unit (ICU) admission, and patient mortality.
Infections were present in 105 (54.6%) patients, and 60 (31.2%) patients had multiple infections during a hospitalization(s) for infections. A total of 201 infections were identified. Urinary tract infections (UTIs) were the most common infection (37.8%), followed by bace of infections in cirrhotic patients is much higher than in their non-cirrhotic counterparts (54.6%), even higher than prior studies suggest. As many of these infections are caused by MDR bacteria and fungal organisms, stronger empiric antibiotics and antifungals should be considered when initially treating this immunocompromised population. However, once organism sensitivities are discovered, narrowing of antibiotic regimens must occur to maintain good antibiotic stewardship.
Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma (HCC), but the rapid growth inherent to such tumor development remains to be explored.
We identified distinct gene coexpression modes upon liver tumor growth using weighted gene coexpression network analysis. Modeling of tumor growth as signaling activity was employed to understand the main cascades responsible for the growth. Hub genes in the modules were determined, examined
, and further assembled into the growth signature.
We revealed modules related to the different growth states in HCC, especially the fastest growth module, which is preserved among different HCC cohorts. Moreover, signaling flux in the cell cycle pathway was found to act as a driving force for rapid growth. Twenty hub genes in the module were identified and assembled into the growth signature, and two genes (
, and
) were tested for their growth potential
. Genetic alteration of the growth signature affected the global gene expression. The activity of the signature was associated with tumor metabolism and immunity in HCC. Finally, the prognosis effect of the growth signature was reproduced in nine cancers.
These results collectively demonstrate the molecule organization of rapid tumor growth in HCC, which is a highly synergistic process, with implications for the future management of patients.
These results collectively demonstrate the molecule organization of rapid tumor growth in HCC, which is a highly synergistic process, with implications for the future management of patients.
Multiple non-invasive methods including radiological, anthropometric and biochemical markers have been reported with variable performance. The present study assessed glycosylated hemoglobin (HbA
) as a biomarker to predict non-alcoholic fatty liver disease (NAFLD) and its severity, compared with body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC).
This case control study included 450 individuals, including 150 cases and 300 age- and gender-matched controls recruited from the Dow Radiology Institute on the basis of radiological findings of fatty infiltration on abdominal ultrasound through convenient sampling. BMI, WHR and WC were measured according to standard protocols. HbA
was determined by turbidimetric inhibition immunoassay.
Among the cases and controls, 66% and 32% had HbA
levels higher than 5.7% respectively. HbA
and BMI were significantly associated with NAFLD [crude odds ratio (cOR)=4.12, 2.88, 2.25 (overweight) and 4.32 (obese)]. WC was found to be significantly associated with NAFLD for both genders (cOR in males=5.
