Predictors of health-related quality of life in patients with chronic liver disease

Background: Patient-reported outcomes such as HRQL have become increasingly important for patients with chronic liver disease (CLD). Aim: To explore the relative impact of different types of liver disease on HRQL as well as predictors of HRQL domains in CLD. Design: Our HRQL databases with Short-Form 36 data (SF-36) as well as clinico-demographic data were used. Scores for each of SF-36 scales (PF - physical functioning, RP - role functioning, BP - bodily pain, GH - general health, VT \u2013 vitality, SF - social functioning, RE - role emotional and MH - mental health, MCS- mental component score, PCS- physical component score) were compared between different types of CLD as well as other variables. SF-36 scales were compared using Wilcoxon tests. Spearman\u2019s rank coefficient was used as a measure of age-HRQL correlations. For all tests and correlation estimations, p-values not exceeding 0.05 after Benjamini-Hochberg correction were considered to be statistically significant. Results: Complete data was available for 1103 CLD patients. Demographic and clinical data included: age 53.7\ub111.8 years, 39% female, 792 (65%) with cirrhosis [357 (45%) Child\u2019s A, 274 (35%) Child\u2019s B and 161 (20%) Child\u2019s C)]. Analysis revealed that age correlated significantly (p<0.05) with worsening HRQL on every scale of the SF-36. Female patients had more HRQL impairments in PF, RP, BP, GH, VT and MH scales of SF-36 (Δ scale score: 6.6-10.7, p<0.05). Furthermore, cirrhotic patients had more impairment of HRQL in every scale of SF-36 (Δ scale score: 6.6-43.0, p<0.05). NAFLD patients had more impairment of HRQL. Conclusions: Analysis of this large cohort with CLD suggests a number of important clinico-demographic factors are associated with HRQL impairment. This data contributes to the full understanding of the total impact of CLD on patients and society

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse-transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention

Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis

Background: Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non-alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized. Aim: This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics. Design: Consecutive patients undergoing bariatric surgery were prospectively recruited. Extensive clinical data and two liver biopsy specimens were obtained at the time of enrollment. A single hepatopathologist reviewed and classified the liver biopsies. Patients with excessive alcohol use and other causes of liver disease were excluded. A group of 29 NASH patients, 12 with steatosis alone, seven obese controls and six non-obese controls were selected for further investigation. Customized cDNA microarrays containing 5220 relevant genes were designed specifically for this study. Microarray experiments were run in triplicate for each sample and a selected group of genes were confirmed using real-time PCR. Outcome measure: Differential hepatic gene expressions in patients with NASH as compared with controls. Results: Thirty-four genes with significant differential expression were identified in patients with NASH when compared with non-obese controls. Moreover, 19 of these genes showed no significant expression differences in obese vs. non-obese controls, suggesting a stronger association of these genes to NASH. Conclusions: Several differentially expressed genes in patients with NASH are related to lipid metabolism and extracellular matrix remodeling. Additionally, genes related to liver regeneration, apoptosis, and the detoxification process were differentially expressed. These findings may help clarify the molecular pathogenesis of NASH and identify potential targets for therapeutic intervention