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Association of Serum Biomarkers With Fatigue in Patients With Chronic Liver Disease
Hemoglobin Level is Associated With the Physical Functioning, Activity, Energy, and Vitality Aspects of Health-Related Quality of Life in Patients With Chronic Hepatitis C (Ch-C) Jillian K. Price, Juhi Moon, Patrice M. Winter, Fatema Nader, Monica Soni, Yun Fang, Lynn Gerber, Zobair M. Younossi Introduction: Fatigue is a common symptom of CH-C, affecting patients' perception of their level of energy, their actual level of activity and their health-related quality of life (HRQL). Successful treatment of this debilitating condition requires identification of potential contributors, using valid HRQL measures/instruments. Aim: 1) To assess the association of hemoglobin over time with patient reported outcomes (PROs) of vitality (VT) and physical functioning (PF) scales of the Medical Outcomes Study Short Form-36 (SF-36) as well as activity and energy domain (AE) of the disease-specific Chronic Liver Disease QuestionnaireHepatitis C version (CLDQ-HCV). 2) To validate CLDQ-HCV using longitudinal hemoglobin and SF-36 data. Methods: We prospectively collected data from 50 CH-C patients who were receiving pegylated interferon and ribavirin (PEG-IFN+RBV). Clinico-laboratory (including hemoglobin) and PRO data were collected for 9 time points (baseline, 4 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 4 weeks follow-up, 12 weeks follow-up and 24 weeks follow-up). CLDQ-HCV's Activity and Energy (AE) domain and the generic SF-36's vitality (VT) and physical functioning (PF) scales were used for primary analysis. Clinico-demographic data were also compared and correlated with these three HRQL domains (AE, PF and VT), representing energy measures. Where longitudinal data were available, Spearman correlation coefficient was used. Z-scores were used to compare scores across questionnaires. Results: A total of 50 CH-C patients receiving pegylated interferon and ribavirin were included: age: 48.5±8.3, 60% male, 60% Caucasians and weight: 81.2±21.5Kg. A total 450 observations' of HRQL and hemoglobin data during treatment and follow-up visits were used. All three measures of energy and activity (PF and VT scales of SF-36 and AE domain of CLDQ-HCV) were highly significantly correlated with each other (VT vs. AE: r=0.83709, p< 0.0001 and VT vs. PF (r=0.48183, p< 0.0001), providing evidence for validity of CLDQHCV. Additionally, hemoglobin positively correlated with the all three HRQL domains (VT: p<0.0001, AE: p< 0.0001, and PF: p=0.0072). Conclusions: 1) PF and VT scales of SF-36 and AE domain of CLDQ-HCV are highly correlated, validating the CLDQ-HCV with a commonly used measure of activity and energy. 2) Hemoglobin is correlated with energy and activity domain of HRQL.
Su1335 Association of Serum Biomarkers With Fatigue in Patients With Chronic Liver Disease Lynn Gerber, Sandra Page, Jillian K. Price, Ancha Baranova, Patrice M. Winter, Zobair M. Younossi Background and Aims: Fatigue is a common symptom of chronic liver diseases (CLD), including non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CH-C). The mechanisms or correlates of fatigue in these patients have not been well studied. We aimed to determine if there is a correlation between self-reports of physical activity associated fatigue (peripheral fatigue) or more global lack of energy and motivation (central fatigue); with serum markers of inflammation, or with abnormalities of glucose and lipid metabolism. Methods: 31 untreated patients (age 52.5 ±6.8 years, 66.7% male, BMI 32.4 ± 5.5, 26.7% DM, 0% cirrhosis) with CLD (biopsy proven NAFLD or CH-C with viremia) participated in the study. Fasting blood samples were obtained and were assessed for levels of cytokines (IL-6, IL-8, and TNF-α), serotonin, C-peptide insulin, liver enzymes (AST, ALT), glucose, and lipids (triglycerides, total cholesterol, HDL, LDL, and the non-HDL fraction). Cytokines, serotonin, and C-peptide insulin were measured by ELISA following the manufacturer's protocols. The remaining parameters were measured by the Cholestech LDX system. Selfreports included standardized and valid measures of depression (short form of CES-D), vitality/energy (vitality subscale of the SF36) and level of activity (Human Activity Profile). Patients were then divided into tertiles by MET value. The middle third was omitted from further analysis; the remaining top third (those with MET >8.8, representing strenuous activity) and bottom third (those with MET <7.5 representing less strenuous activity) became “high MET” (i.e. not fatigued) and “low MET” (fatigued) groups; respectively. Central fatigue was defined as having a CES-D score >7 and a transformed vitality index score <45. Only patients meeting these criteria were defined as having central fatigue. Groupwise comparisons were made by Mann-Whitney test, and correlations were assessed by Spearman Rho. Results: In comparison to CLD patients without peripheral fatigue, CLD patients who had peripheral fatigue (n=23) had significantly elevated serum levels of IL-6 (7.2±13.5 pg/mL vs. 1.6±0.74 pg/mL, p<0.01) and IL-8 (22.8±11.2 vs. 15.7±6.8 pg/mL, p<0.05); respectively. In terms of central fatigue, the ratio of AST/ALT was significantly lower in CLD patients with central fatigue than those CLD patients without central fatigue (0.862±0.166 vs. 1.118±0.283, p= 0.004). Conclusions: The current study demonstrates that a substantial majority of patients with CLD report significant peripheral fatigue. This type of fatigue is linked to elevated serum levels of IL-6 and IL-8, implying an inflammatory component present in patients with peripheral fatigue but not in those with central fatigue. Further study into the nature and extent of fatigue associated with CLD is warranted.
Su1338 The Influence of Hemodialysis to Prognosis of Patients With Severe Alcoholic Lactic Acidosis Jong Kyu Park, Sang Jin Lee, Koon Hee Han, Young Don Kim, Woo Jin Jeong, Gab Jin Cheon Background/Aims: Alcoholic lacticacidosis is a metabolic disturbance that is caused by prolonged and excessive alcohol consumption. Treatment of patients with alcoholic lactic acidosis are rapid volume resuscitation and correction of electrolyte inbalance. Also, Continuous renal replacement therapy (CRRT) to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of the alcohol-related intoxications. METHODS: The aim of our study is to evaluate the change of mortality in alcoholic lactic acidosis patients treated with continuous veno-venous hemofiltration (CVVH). The medial record of patient with alcoholic lactic acidosis admitted to our hospital from Jan 2003 to July 2010 were retrospectively analyzed. Patients were divided into two groups according to CVVH. RESULTS: Total number of patients who diagnosed with alcoholic lactic acidosis is 52. The 52 patients included 4(7.6%) women and 48(92.4%) men with a mean age of 52±16 years old. 19 patients(36%) rceived CVVH. Overall mortality rate was 61% (n=36) and mean survival duration was 26.3 hours. A mortality rate of dialysis group was significantly low as compared to non-dialysis group (52% vs 72%, p<0.05). Interestingly, the cumulative survival rate were better in early dialysis group than in later. Mortality was significantly correlated with the hemodialysis status and dialysis starting time. CONCLUSION: The dialysis treatment of patients with alcoholic lactic acidosis improves the survival especially if it can be initiated as soon as possible.
Su1336 The Influence of Serum MMP-2 Activity on the Development of Liver Fibrosis in Patients With Alcoholic Liver Cirrhosis Agnieszka Madro, Grazyna Czechowska, Maria Slomka, Krzysztof Celinski, Stanislawa Szymonik-Lesiuk, Jacek Kurzepa
Su1339 Spontaneous Bacterial Peritonitis and Proton Pump Inhibitors: Correlation of Disease Process? Sameer Islam, Ebtesam A. Islam, Wesam Frandah, Amber Moreland, Sherazad Islam, Kenneth Nugent
Background: Alcoholic liver cirrhosis is a major problem in the Western World. Liver biopsy is a “gold standard” for fibrosis assessment however numerous patients have contraindications to this procedure. The most promising noninvasive marker is APRI score, which usefulness was confirmed in patients with chronic hepatitis C infection. Another markers could be matrix metalloproteinases, which are responsible for the degradation of extracellular matrix. The aim of the study was to evaluate the gelatinase activities (MMP-2 and MMP-9) as the prognostic markers of fibrosis in patients with different stages of alcoholic liver cirrhosis. Methods: Sixty seven patients presented various stages of alcoholic liver cirrhosis according to Child-Pough criteria and 26 healthy control subjects were enrolled. The blood samples were collected for MMP-2 and MMP-9 activities, AlAt, AspAt, GGTP activity, bilirubin level and platelet count. APRI and GAPRI scores were calculated. Results: A significant decrease of serum MMP-2 activity was noted in stages B and C of liver cirrhosis in comparison with control. Serum MMP-9 activity did not depends on the stage of liver cirrhosis. APRI and GAPRI gradually increased according to the progress of liver cirrhosis and have the greatest value in stages C. The statistically significant relationship between APRI vs. MMP-2 (r = -0.03), APRI vs. MMP-9 (r = -0.18), GAPRI vs. MMP-2 (r = -0.18) and GAPRI vs MMP-9 (r = -0.21) were not observed. Conclusions: The activity of MMP-2 but not MMP-9 may be useful in the assessment of fibrosis degree in the alcoholic liver cirrhosis. APRI/MMP2, APRI/ MMP9, GAPRI/MMP2 and GAPRI/MMP9 correlations cannot be considered as the useful marker of fibrosis in alcoholic liver cirrhosis.
Purpose of Study: Bacterial infections are a significant cause of morbidity and mortality in cirrhosis, the most common of which is spontaneous bacterial peritonitis (SBP). Proton pump inhibitors (PPI) are widely used medications to treat peptic ulcer disease to eliminate gastric acid in the stomach and relieve symptoms. This, however, allows orally ingested bacteria to colonize and proliferate in the stomach and small intestine, thereby increasing bacterial overgrowth and leading to SBP. We explored this association in a communitybased setting using a retrospective chart review. Methods Used: We conducted a 5-year retrospective review of patients at a teaching hospital diagnosed with ascites, cirrhosis, and SBP using ICD 9 codes from January 1st 2004 to December 31st 2008. Each patient with a diagnosis of ascites, cirrhosis, and SBP was stratified into two groups: one with home PPI use (Study), and those without home PPI use (Control). Both groups were matched 1:1 based on age (decade), sex, Child-Turcotte-Pugh (CTP) scores, and MELD scores (intervals of 10). Summary of Results: Eight patients had a diagnosis of ascites, cirrhosis, and SBP and were on a home PPI regime; they were matched with eight control patients. The mean age of the both groups was 51 yrs +/- 6.8 SD; PPI group of patients was slightly older than the control group (53.7+/- 9.7 vs 49.7+/- 4.2, p-value <0.35). 90% of all the patients in both groups were males. We found no significant difference between the two groups in terms of CTP or MELD score severity. The PPI group had a lower ascitic fluid albumin level (0.55 +/- 0.5, CI 0.3 - 1.05) than the control group. Mortality was 25% higher in the PPI
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Su1335 Association of Serum Biomarkers With Fatigue in Patients With Chronic Liver Disease Lynn Gerber, Sandra Page, Jillian K. Price, Ancha Baranova, Patrice M. Winter, Zobair M. Younossi Background and Aims: Fatigue is a common symptom of chronic liver diseases (CLD), including non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CH-C). The mechanisms or correlates of fatigue in these patients have not been well studied. We aimed to determine if there is a correlation between self-reports of physical activity associated fatigue (peripheral fatigue) or more global lack of energy and motivation (central fatigue); with serum markers of inflammation, or with abnormalities of glucose and lipid metabolism. Methods: 31 untreated patients (age 52.5 ±6.8 years, 66.7% male, BMI 32.4 ± 5.5, 26.7% DM, 0% cirrhosis) with CLD (biopsy proven NAFLD or CH-C with viremia) participated in the study. Fasting blood samples were obtained and were assessed for levels of cytokines (IL-6, IL-8, and TNF-α), serotonin, C-peptide insulin, liver enzymes (AST, ALT), glucose, and lipids (triglycerides, total cholesterol, HDL, LDL, and the non-HDL fraction). Cytokines, serotonin, and C-peptide insulin were measured by ELISA following the manufacturer's protocols. The remaining parameters were measured by the Cholestech LDX system. Selfreports included standardized and valid measures of depression (short form of CES-D), vitality/energy (vitality subscale of the SF36) and level of activity (Human Activity Profile). Patients were then divided into tertiles by MET value. The middle third was omitted from further analysis; the remaining top third (those with MET >8.8, representing strenuous activity) and bottom third (those with MET <7.5 representing less strenuous activity) became “high MET” (i.e. not fatigued) and “low MET” (fatigued) groups; respectively. Central fatigue was defined as having a CES-D score >7 and a transformed vitality index score <45. Only patients meeting these criteria were defined as having central fatigue. Groupwise comparisons were made by Mann-Whitney test, and correlations were assessed by Spearman Rho. Results: In comparison to CLD patients without peripheral fatigue, CLD patients who had peripheral fatigue (n=23) had significantly elevated serum levels of IL-6 (7.2±13.5 pg/mL vs. 1.6±0.74 pg/mL, p<0.01) and IL-8 (22.8±11.2 vs. 15.7±6.8 pg/mL, p<0.05); respectively. In terms of central fatigue, the ratio of AST/ALT was significantly lower in CLD patients with central fatigue than those CLD patients without central fatigue (0.862±0.166 vs. 1.118±0.283, p= 0.004). Conclusions: The current study demonstrates that a substantial majority of patients with CLD report significant peripheral fatigue. This type of fatigue is linked to elevated serum levels of IL-6 and IL-8, implying an inflammatory component present in patients with peripheral fatigue but not in those with central fatigue. Further study into the nature and extent of fatigue associated with CLD is warranted.
Su1338 The Influence of Hemodialysis to Prognosis of Patients With Severe Alcoholic Lactic Acidosis Jong Kyu Park, Sang Jin Lee, Koon Hee Han, Young Don Kim, Woo Jin Jeong, Gab Jin Cheon Background/Aims: Alcoholic lacticacidosis is a metabolic disturbance that is caused by prolonged and excessive alcohol consumption. Treatment of patients with alcoholic lactic acidosis are rapid volume resuscitation and correction of electrolyte inbalance. Also, Continuous renal replacement therapy (CRRT) to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of the alcohol-related intoxications. METHODS: The aim of our study is to evaluate the change of mortality in alcoholic lactic acidosis patients treated with continuous veno-venous hemofiltration (CVVH). The medial record of patient with alcoholic lactic acidosis admitted to our hospital from Jan 2003 to July 2010 were retrospectively analyzed. Patients were divided into two groups according to CVVH. RESULTS: Total number of patients who diagnosed with alcoholic lactic acidosis is 52. The 52 patients included 4(7.6%) women and 48(92.4%) men with a mean age of 52±16 years old. 19 patients(36%) rceived CVVH. Overall mortality rate was 61% (n=36) and mean survival duration was 26.3 hours. A mortality rate of dialysis group was significantly low as compared to non-dialysis group (52% vs 72%, p<0.05). Interestingly, the cumulative survival rate were better in early dialysis group than in later. Mortality was significantly correlated with the hemodialysis status and dialysis starting time. CONCLUSION: The dialysis treatment of patients with alcoholic lactic acidosis improves the survival especially if it can be initiated as soon as possible.
Su1336 The Influence of Serum MMP-2 Activity on the Development of Liver Fibrosis in Patients With Alcoholic Liver Cirrhosis Agnieszka Madro, Grazyna Czechowska, Maria Slomka, Krzysztof Celinski, Stanislawa Szymonik-Lesiuk, Jacek Kurzepa
Su1339 Spontaneous Bacterial Peritonitis and Proton Pump Inhibitors: Correlation of Disease Process? Sameer Islam, Ebtesam A. Islam, Wesam Frandah, Amber Moreland, Sherazad Islam, Kenneth Nugent
Background: Alcoholic liver cirrhosis is a major problem in the Western World. Liver biopsy is a “gold standard” for fibrosis assessment however numerous patients have contraindications to this procedure. The most promising noninvasive marker is APRI score, which usefulness was confirmed in patients with chronic hepatitis C infection. Another markers could be matrix metalloproteinases, which are responsible for the degradation of extracellular matrix. The aim of the study was to evaluate the gelatinase activities (MMP-2 and MMP-9) as the prognostic markers of fibrosis in patients with different stages of alcoholic liver cirrhosis. Methods: Sixty seven patients presented various stages of alcoholic liver cirrhosis according to Child-Pough criteria and 26 healthy control subjects were enrolled. The blood samples were collected for MMP-2 and MMP-9 activities, AlAt, AspAt, GGTP activity, bilirubin level and platelet count. APRI and GAPRI scores were calculated. Results: A significant decrease of serum MMP-2 activity was noted in stages B and C of liver cirrhosis in comparison with control. Serum MMP-9 activity did not depends on the stage of liver cirrhosis. APRI and GAPRI gradually increased according to the progress of liver cirrhosis and have the greatest value in stages C. The statistically significant relationship between APRI vs. MMP-2 (r = -0.03), APRI vs. MMP-9 (r = -0.18), GAPRI vs. MMP-2 (r = -0.18) and GAPRI vs MMP-9 (r = -0.21) were not observed. Conclusions: The activity of MMP-2 but not MMP-9 may be useful in the assessment of fibrosis degree in the alcoholic liver cirrhosis. APRI/MMP2, APRI/ MMP9, GAPRI/MMP2 and GAPRI/MMP9 correlations cannot be considered as the useful marker of fibrosis in alcoholic liver cirrhosis.
Purpose of Study: Bacterial infections are a significant cause of morbidity and mortality in cirrhosis, the most common of which is spontaneous bacterial peritonitis (SBP). Proton pump inhibitors (PPI) are widely used medications to treat peptic ulcer disease to eliminate gastric acid in the stomach and relieve symptoms. This, however, allows orally ingested bacteria to colonize and proliferate in the stomach and small intestine, thereby increasing bacterial overgrowth and leading to SBP. We explored this association in a communitybased setting using a retrospective chart review. Methods Used: We conducted a 5-year retrospective review of patients at a teaching hospital diagnosed with ascites, cirrhosis, and SBP using ICD 9 codes from January 1st 2004 to December 31st 2008. Each patient with a diagnosis of ascites, cirrhosis, and SBP was stratified into two groups: one with home PPI use (Study), and those without home PPI use (Control). Both groups were matched 1:1 based on age (decade), sex, Child-Turcotte-Pugh (CTP) scores, and MELD scores (intervals of 10). Summary of Results: Eight patients had a diagnosis of ascites, cirrhosis, and SBP and were on a home PPI regime; they were matched with eight control patients. The mean age of the both groups was 51 yrs +/- 6.8 SD; PPI group of patients was slightly older than the control group (53.7+/- 9.7 vs 49.7+/- 4.2, p-value <0.35). 90% of all the patients in both groups were males. We found no significant difference between the two groups in terms of CTP or MELD score severity. The PPI group had a lower ascitic fluid albumin level (0.55 +/- 0.5, CI 0.3 - 1.05) than the control group. Mortality was 25% higher in the PPI
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