Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC. PATIENTS: All patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. The 10-year cardiovascular risk was estimated by the Framingham risk score. RESULTS: Fifty four patients with PBC were included and compared to 106 controls. Differences in total cholesterol (263.8±123.9mg/dl vs. 199.6±40, p=0.0001), LDL-cholesterol (179.3±114.8 vs. 126.8±34.7, p=0.0001), HDL-cholesterol (62.4±36.2mg/dl vs. 47.3±12.3, p=0.0001) and triglycerides (149.1±59.1mg/dl vs. 126.4±55.4, p=0.001) were found. Hypercholesterolemia (>240mg/dl) was found in 52.4% of the patients with PBC vs. 11% in the control group, high LDL-cholesterol (160-189mg/dl) in 45.2% of the patients with PBC vs. 10% in controls and hyperalphalipoproteinemia (HDL-cholesterol >60mg/dl) in 45.2% of the patients with PBC vs. 16% in controls. The 10-year cardiovascular risk was 5.3%±5.9 in the patients with PBC and 4.1%±5.7 in the control group (p=0.723, IC 95%=0.637-1.104). Only one cardiovascular event (stroke) in a patient with PBC was registered in a mean follow up time of 57.9±36.5 months. CONCLUSIONS: Marked derangements in serum lipids and a high frequency of dyslipidemias are found in patients with PBC, however, these do not increase the risk of cardiovascular events.

[A 35-year report of the study of group on gastrointestinal cancer in Mexico City: variations in frequency of different digestive tract neoplasms among different socioeconomic statuses]. / Variaciones en la frecuencia de cáncer del aparato digestivo en el transcurso de 35 años en cuatro instituciones de la Ciudad de México de distinto nivel socioeconómico.

BACKGROUND: Since the middle of the last century, North America and occidental countries have reported variations in the frequency of gastrointestinal neoplasms. Several environmental factors, mainly nutritional and dietary exposure, as well as habits have contributed to these changes. We have documented these changes in Mexico during the last 35 years. AIMS: To define the epidemiologic changes of gastrointestinal neoplasms during the last three decades in our population. METHODS: We summarized the evidence of an observational study, registering the frequency of different gastrointestinal malignancies from four institutions of socioeconomically different populations in Mexico City during 35 years. The Mexican National Academy of Medicine supported this effort. During this period, two nutritional surveys took place, letting us define the relationship between dietary changes and cancer occurrence. RESULTS: Replacement of gastric cancer by colorectal cancer as the leading gastrointestinal malignancy. Relationship between cancer and diet changes. Increase of esophageal adenocarcinoma in relation to epidermoid carcinoma secondary to gastroesophageal reflux and Barrett's esophagus rising incidence. Gall bladder cancer had a high frequency in one institution, probably related to genetic and racial factors. CONCLUSIONS: This epidemiologic data should lead us to implement sanitary measures for the prevention, early diagnosis, and appropriate treatment of gastrointestinal neoplasms.

Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis.

OBJECTIVE: Alcoholic hepatitis (AH) is a severe clinical condition that needs novel therapies. The identification of targets for therapy is hampered by the lack of animal models of advanced AH. The authors performed a translational study through a transcriptome analysis in patients with AH to identify new molecular targets. DESIGN: Hepatic gene expression profiling was assessed by DNA microarray in patients with AH (n=15) and normal livers (n=7). Functional analysis was assessed by gene set enrichment analysis. Quantitative PCR was performed in patients with AH (n=40), hepatitis C (n=18), non-alcoholic steatohepatitis (n=20) and in mouse models of acute and chronic liver injury. Protein expression was assessed by immunohistochemistry and western blotting. RESULTS: Gene expression analysis showed 207 genes >5-fold differentially expressed in patients with AH and revealed seven pathways differentially regulated including 'cytokine-cytokine receptor interaction'. Several tumour necrosis factor (TNF) superfamily receptors, but not ligands, were overexpressed in AH. Importantly, Fn14 was the only TNF superfamily receptor exclusively upregulated in AH compared with other liver diseases and correlated with both 90-day mortality and severity of portal hypertension. Fn14 protein expression was detected in areas of fibrogenesis and in a population of hepatocytes. Fn14 expression was increased in experimental models of liver injury and was detected in progenitor cells. CONCLUSION: Translational research revealed that TNF superfamily receptors are overexpressed in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with AH. TNF superfamily receptors could represent a potential target for therapy.

AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis.

Liver biopsy is the recognized gold standard for liver fibrosis staging. The aspartate aminotransferase to platelet ratio index (APRI) has been proposed as a noninvasive and readily available tool for the assessment of liver fibrosis in chronic hepatitis C (CHC). This study aimed to validate, in a Mexican tertiary health care setting, the diagnostic usefulness of APRI in CHC, nonalcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH). In an observational, cross-sectional, comparative and retrolective fashion, consecutive patients with CHC, NAFLD or AIH were evaluated. Fibrosis was staged using the METAVIR scale. Receiver operating characteristic ROC curves were constructed for significant fibrosis, advanced fibrosis and cirrhosis. One-hundred-sixty-four CHC, 30 NAFLD and 42 AIH patients were evaluated. For the diagnosis of significant fibrosis, APRI values delimited an area under de ROC curve (AUC) of 0.776 in CHC, 0.564 in NAFLD, and 0.602 in AIH patients. For advanced fibrosis, the AUCs were 0.803, 0.568 and 0.532 in CHC, NAFLD and AIH patients, respectively. For cirrhosis, AUCs were 0.830 and 0.599 in CHC and AIH patients. In conclusion, APRI can be a useful noninvasive alternative for the diagnosis of significant fibrosis and cirrhosis in our CHC patients. APRI values of < or = 0.3 and < or = 0.5 rule out significant fibrosis and cirrhosis, and a value of > or = 1.5 rules in significant fibrosis. In patients with NAFLD, APRI values tend to increase with the degree of fibrosis, suggesting that it could be useful in this disease. APRI appears to be of no value in patients with AIH.