Measurement of health-related quality of life in patients with chronic liver disease.
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Adaptation, Psychological↗
Biomedical subjects
Zobair M Younossi
Publications and source records attributed to Zobair M Younossi.
Quality of life and liver transplantation in patients with polycystic liver disease.
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Cysts↗
Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.
BACKGROUND: Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. METHODS: Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). RESULTS: Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). CONCLUSIONS: Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.
Adult↗
Q: How often should patients with hepatitis C be screened for esophageal varices?
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Esophageal and Gastric Varices↗
Depression, anemia and health-related quality of life in chronic hepatitis C.
BACKGROUND/AIMS: Hepatitis C (HCV) infected patients have significant health-related quality of life (HRQL) impairment which worsens during anti-viral therapy. Our aim was to examine the association of HRQL with treatment-induced depression and anemia. METHODS: Two hundred and seventy-one HCV patients who received pegylated interferon alfa 2b and ribavirin were included. Data on HRQL, depressive symptoms, laboratory values and socio-demographic characteristics were collected. RESULTS: Mean age was 47.1+/-6.5, 69% were male, and 73% were White. HCV patients' HRQL declined during anti-viral therapy but returned to or exceeded baseline levels within 24 weeks of completion. Anemia and depression were both associated with HRQL impairment. The effects of depression on HRQL were strong; once depression scores were included other factors were no longer significant. Patients' depressive symptoms tended to increase during the initial half of treatment regimen. Those with higher body mass index (BMI), cirrhosis, and women reported more HRQL impairments. HRQL scales were generally not associated with alcohol abuse, age, race, ALT and HCV RNA levels. CONCLUSIONS: Anti-viral therapy for HCV is associated with diminished HRQL. Although anemia and depression were associated with this impairment, depression was the most consistent predictor. Future studies are needed to see whether proactive management of these side effects can improve patients' HRQL and the efficacy of antiviral therapy for hepatitis C.
Adult↗
Impact of hepatitis C on health related quality of life: a systematic review and quantitative assessment.
Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF-36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF-36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Case-Control Studies↗
Morbid obesity, nonalcoholic fatty liver disease, and weight loss surgery.
OBJECTIVE: This study examines the impact of biliopancreatic diversion, a malabsorptive variant of gastric bypass, on liver histology. METHODS: Liver samples were collected from 689 severely obese (BMI 47 +/- 9 kg m(2)) patients undergoing biliopancreatic diversion. Exclusion criteria included: history of hepatitis, exposure to hepatotoxic medications, prior weight loss surgery, and alcohol consumption greater than 100 grams per week. One group of 14 patients had cirrhosis in their initial biopsy. Eleven of those 14 patients underwent multiple biopsies to monitor their liver disease. A second group of 104 patients had re-operations and a second liver biopsy. A hepatopathologist conducted blind evaluations of all biopsy specimens looking for steatosis and fibrosis. RESULTS: All patients lost weight and showed improvement in their metabolic syndrome. Of the 104 patients undergoing re-operation with a second liver biopsy, 28 showed a decrease in severe fibrosis, while 42 patients developed mild fibrosis. On average, this group lost 38 +/- 18 kg over 41 +/- 25 post-surgical months. A sub-group analysis revealed an association between increased fibrosis and post-operative low serum albumin, diarrhea, pre-operative alcohol consumption, and menopausal status. The eleven patients with cirrhosis in their initial biopsy showed a reduction in their fibrosis grade (mean fibrosis grade from 5 to 3) during nine years of follow-up care. CONCLUSION: These findings indicate that significant weight loss after biliopancreatic diversion can improve liver histology in patients with advanced fibrosis.
Biliopancreatic Diversion↗
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.
Adult↗
MELD fails to measure quality of life in liver transplant candidates.
Previous studies have demonstrated an association between Child Turcotte-Pugh (CTP) class and impaired quality of life. However, the relationship between the model for end-stage liver disease (MELD) score and quality of life (QOL) has not been well studied. In this study, quality of life questionnaires (Medical Outcomes Short Form 36 [SF-36] and the Chronic Liver Disease Questionnaire [CLDQ]) were administered to 150 adult patients awaiting liver transplantation. We also collected demographic data and laboratory results and recorded manifestations of hepatic decompensation. The study found that all domains of the SF-36 and CLDQ were significantly lower in our patient cohort than in normal controls (P < .001). There was a moderate negative correlation between CPT class and physical components of the SF-36 (r = -.30), while there was a weak negative correlation (r = -.10) between CPT class and the mental component. There was a negative moderate correlation between CPT class and overall CLDQ (r = -.39, P < .001) and a weak correlation (r = -.20) between MELD score and overall CLDQ score. Both encephalopathy (correlation coefficient = -.713, P = .004) and ascites (correlation coefficient = -.68, P = .006) were predictive of the QOL using CLDQ (adjusted R(2) = .1494 and f = 0.000). In conclusion, in liver transplant candidates, the severity of liver disease assessed by the MELD score was not predictive of QOL. The presence of ascites and/or encephalopathy was significantly associated with poor quality of life. CTP correlates better to QOL, probably because it contains ascites and encephalopathy.
Female↗
Pegylated interferon alpha-2b, ribavirin and amantadine for chronic hepatitis C.
In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon alpha-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon alpha-2b at a dose of 1.5 microg/kg weekly with ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon alpha-2b, 0.5 microg/kg weekly, ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (<50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27+/-5.76 years; their body mass index (BMI) was 28.87+/-5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242+/-698,030 IU/mL, with a baseline ALT of 107.25+/-79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin, < 10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin, <8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0-2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon alpha-2b and ribavirin does not seem to increase the efficicacy of this regimen.
Adult↗
Approach to the diagnosis and treatment of nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It describes several clinicopathologic entities from simple hepatic steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. This article describes the epidemiology, clinical features, natural history, and pathogenesis of NAFLD.
Carcinoma, Hepatocellular↗
Erythropoietic growth factors for treatment-induced anemia in hepatitis C: a cost-effectiveness analysis.
BACKGROUND & AIMS: Treatment-induced anemia undermines the efficacy of antiviral therapy in hepatitis C by mandating ribavirin dose reduction and diminishing adherence to therapy. Erythropoietic growth factors (EGFs) may correct treatment-induced anemia, facilitate maintenance of full-dose therapy, and improve rates of sustained virologic response (SVR). We sought to determine the cost effectiveness of adjunctive treatment with an EGF vs standard care in the treatment of hepatitis C. METHODS: We used a decision analysis to calculate the cost effectiveness of 2 treatment strategies for a patient cohort with chronic hepatitis C, increased transaminase levels, and no cirrhosis who were receiving pegylated-interferon and ribavirin (RBV): (1) RBV dose-reduction for anemia, followed by discontinuation of therapy if anemia persisted (standard care strategy), (2) adjunctive treatment with EGF therapy for anemia, with RBV dose reduction reserved for persistent anemia despite EGF therapy (EGF strategy). We conducted cost-effectiveness and cost-utility analyses to compare short- and long-term outcomes between the strategies. RESULTS: The percentage achieving SVR was 52.3% in the standard care strategy and 59.5% in the EGF strategy. Compared with standard care, the EGF strategy cost an incremental $36,568 per unadjusted life-year gained and $16,443 per quality-adjusted life-year gained. In a sensitivity analysis, if a third-party payer was willing to pay $50,000 per quality-adjusted life-year gained for the use of an EGF, then 86.1% of patients would be within the budget. CONCLUSIONS: Compared with standard care, adjunctive therapy with an EGF for the management of treatment-induced anemia may increase the probability of achieving SVR, increase unadjusted lifespan, and increase quality-adjusted lifespan at an acceptable cost.
Anemia↗
The use of growth factors to manage the hematologic side effects of PEG-interferon alfa and ribavirin.
Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.
Anemia, Hypochromic↗
High rates of uninsured among HCV-positive individuals.
BACKGROUND AND GOALS: There are no published data on the health insurance status of Hepatitis C virus (HCV)-positive individuals. To address this issue, we analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). STUDY: Individuals 18 years of age and older who participated in NHANES III were included in the study. We determined the rates of health insurance coverage according to HCV status. We also determined healthcare status and health service utilization according to health insurance status among HCV-positive persons. RESULTS: HCV-positive individuals were more likely to be uninsured compared with those who were HCV-negative (29.6% vs. 12.2%, P = 0.0002). Among those with health insurance, HCV-positive individuals were more likely to have government insurance compared with those who were HCV-negative (42.9% vs. 27.6%, P < 0.005). Among HCV-positive individuals, being uninsured was associated with younger age, being unmarried, living in the South, Mexican-American race/ethnicity, and not graduating from high school. Additionally, the uninsured were less likely than their insured counterparts to identify a healthcare facility for sick or routine care, and less likely to have regular contact with a healthcare professional. CONCLUSIONS: A high proportion of HCV-positive individuals are uninsured, and many HCV-positive individuals with health insurance have publicly funded insurance. This finding may have implications for access to health care and for liver-related disease outcomes in HCV-positive persons.
Adolescent↗
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.
Adult↗
Microarray technology in the study of obesity and non-alcoholic fatty liver disease.
The recent development of high-throughput gene expression technology permits simultaneous investigation of thousands of genes, providing a snapshot of the transcription state of diseased tissue. Microarray-based expression profiling is well suited to investigate the molecular basis of complex diseases such as obesity and chronic liver disease. With the help of microarray technology, functional genomics will surely advance our understanding of these diseases, and lead to more effective, targeted interventions that lack the toxicity of many conventional treatments. Despite their tremendous potential, microarray studies are subject to potential flaws in experimental design, experimental techniques, data analysis, and data interpretation. Besides the technical issues, the most important challenge is to develop integrative databases that combine gene expression data with the clinical data. Over the next few years, advances in technology and refinements in study design and data analysis will make clinically relevant translational research even more engaging and productive.
Fatty Liver↗
Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients.
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease in the United States. It is commonly associated with the components of the metabolic syndrome including obesity. From the spectrum of NAFLD, only patients with nonalcoholic steatohepatitis (NASH) have been convincingly shown to have a potential for progression to cirrhosis. We report the prevalence of NAFLD and NASH as well as predictors of NASH and advanced fibrosis in morbidly obese patients. METHODS: 212 consecutive patients who underwent bariatric surgery were enrolled in the study. A liver biopsy was performed at the time of the surgery. Causes of chronic liver disease other than NAFLD were excluded by clinical and laboratory evaluation. RESULTS: The prevalence of NAFLD was 93%. Of those with NAFLD, 26% had NASH. 17 patients (9%) had advanced fibrosis (i.e., bridging fibrosis or cirrhosis). Male gender, AST, and type 2 diabetes mellitus were independently associated with NASH. Waistto-hip ratio, AST, and focal hepatocyte necrosis on liver biopsy were independently associated with advanced fibrosis. Interestingly, while AST was associated with NASH and advanced fibrosis, the majority of the patients with either NASH or advanced fibrosis had normal AST. CONCLUSIONS: NAFLD and NASH are very common in morbidly obese patients undergoing bariatric surgery. Features associated with the metabolic syndrome and liver cell injury are independently associated with either NASH or advanced fibrosis.
Adult↗
Nonalcoholic Steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is an important medical condition and there is great public health concern related to its increasing incidence and potential implications for the development of end-stage liver disease. NASH represents a progression beyond simple lipid deposition in the liver parenchyma, requiring histologic evidence for hepatocyte injury such as ballooning degeneration, Mallory bodies, and/or pericellular fibrosis that can potentially lead to progressive liver injury and eventually cirrhosis. It is believed that several insults contribute to the evolution of hepatic injury such as insulin dysregulation, lipid deposition, oxidative free radicals, and lipid perioxidation. Initial treatment protocols for NASH focus on various aspects of injury in an attempt to control insulin imbalances, improve lipid regulation, reduce free radicals, and ameliorate the inflammatory process. No therapy is conclusively beneficial in all individuals, but preliminary data suggest several approaches that hold promise.
Journal Article↗