Background: Abnormal hematological indices (HI) are common in cirrhosis from hepatitis C virus (H... more Background: Abnormal hematological indices (HI) are common in cirrhosis from hepatitis C virus (HCV). Eradication of HCV may ameliorate these abnormalities. The objectives of the current study were to assess whether HI improve with HCV eradication and whether they can predict prognosis in patients with cirrhosis during and after completion of antiviral therapy. Methods: A retrospective cohort study of 153 patients with HCV cirrhosis treated with Peg-interferon and ribavirin was conducted. The primary endpoint was improvement in HI after successful antiviral therapy. The secondary outcome was clinical decompensation during and after completion of antiviral therapy and association with HI. A repeated measures 2-way ANOVA was performed to compare means. Multivariate analysis was used to identify predictors of clinical decompensation. Results: One hundred fifty three patients met study criteria. The rate of sustained virological rate was 26%. Median follow-up was 55 months. Platelet and WBC counts improved with HCV eradication compared to those in whom treatment was unsuccessful (p < 0.05). On univariate analysis, the presence of thrombocytopenia was associated clinical decompensation prior to, on treatment and after completion of therapy. Thrombocytopenia (OR 14.8, p-value <0.001) after completing treatment predicted clinical decompensation when controlled for albumin, MELD and age in multivariate analysis at 6 months after completion of therapy. Conclusions: Platelet and leukocyte counts improve in patients with cirrhosis who respond to antiviral therapy against HCV. The presence of thrombocytopenia predicts decompensation on treatment and after completion of therapy.
Results from prospective controlled trials do not justify the use of either prophylactic shunt su... more Results from prospective controlled trials do not justify the use of either prophylactic shunt surgery or sclerotherapy for the prevention of initial variceal bleeding. Use of nonselective beta-adrenergic blockers has been shown to reduce significantly the risk of first variceal hemorrhage, but their effect on survival is marginal. Because only 25% to 40% of patients with cirrhosis and varices experience variceal bleeding, is it justified to place all patients with varices on beta-blocker therapy? The answer lies in the identification of a high-risk population (i.e., patients with large varices and endoscopic red color signs) and patients who can tolerate and will be compliant with therapy. The duration of therapy required is unknown and perhaps requires a lifetime commitment. Future research will involve the use of combinations of pharmacologic agents to reduce further portal pressure and perhaps the use of pharmacologic agents and sclerotherapy. The goal of a significant improveme...
This report describes a middle-aged female who received imipramine for 7 days, developed severe c... more This report describes a middle-aged female who received imipramine for 7 days, developed severe cholestatic jaundice with features similar to primary biliary cirrhosis, and then improved clinically over the next 12 mo. Biochemical and histologic abnormalities persisted over a 14-yr period of follow-up, though subsequent administration of haloperidol may have influenced the long-term course. High levels of circulating immune complexes were also found 14 yr later, which raises questions about the relationship of primary biliary cirrhosis to drug-induced liver injury. A review of the literature on imipramine- and phenothiazine-related hepatic injuries reveals multiple similarities, and this case provides further evidence for a common hepatic reaction to the two drugs.
Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of s... more Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis. Compare mortality in patients with cirrhosis on statins to those not on statins. A retrospective cohort study evaluated patients from 1988 to 2011 at Partners Healthcare Hospitals. The Partners Research Patient Data Registry identified patients with biopsy-proven cirrhosis on statins at biopsy and at least 3 months following. Controls were matched 1:2 by age, gender and Child-Pugh class. Decompensation was defined as ascites, jaundice/bilirubin &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2.5 mg/dL, and/or hepatic encephalopathy or variceal hemorrhage. Primary outcome was mortality. Secondary outcome was decompensation in baseline-compensated patients. Chi-square and two-way ANOVA testing compared groups. Cox proportional hazards models for mortality controlled for age, Child-Pugh class, diabetes, coronary artery disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Kaplan-Meier curves graphed mortality. Eighty-one statin users and 162 controls were included. Median follow-up: 36 months in statin users and 30 months in controls. 70.4% of patients were Child-Pugh A. Model for End-Stage Liver Disease (MELD), albumin, varices and beta-blocker use were not significantly different between groups. Statin users had lower mortality on multivariate analysis (HR 0.53, p = 0.01), and Child-Pugh A patients had longer survival on Kaplan-Meier analysis. Cox multivariate analysis for decompensation showed lower risk of decompensation with statins while increased decompensation with low albumin, high MELD score and beta-blocker use. In patients with cirrhosis, statin therapy is not associated with increased mortality and may delay decompensation.
Page 1. SESSION 4 Primary Prophylaxis for Variceal Bleeding Norman D. Grace, Juan Carlos Garcia-P... more Page 1. SESSION 4 Primary Prophylaxis for Variceal Bleeding Norman D. Grace, Juan Carlos Garcia-Pagan, Mario Angelico, Richard Moreau, Agustin Albillos, Michael Schepke, Thomas D. Boyer and Naga Chalasani INTRODUCTION ...
Liver biopsy is the gold standard for establishing cirrhosis, but may provide inadequate tissue f... more Liver biopsy is the gold standard for establishing cirrhosis, but may provide inadequate tissue for interpretation in some patients. The aim of this study was to determine whether the hepatic venous pressure gradient predicts the presence of cirrhosis. Patients with liver disease who had undergone hepatic venous pressure gradient measurements were identified. Clinical, laboratory, and hepatic venous pressure gradient data were collected and biopsies were staged for fibrosis. Univariable logistic regression was used to identify potential predictors of cirrhosis. Multivariable logistic regression was applied to determine adjusted odds ratios. Thirty-two patients were included. The hepatic venous pressure gradient was an independent predictor of cirrhosis. On multivariable analysis, the hepatic venous pressure gradient predicted cirrhosis, with an odds ratio of 1.46 (95% confidence interval 1.05-2.02, P=0.023). Using a cutoff of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=6.5 mm Hg, the hepatic venous pressure gradient was 86% sensitive and 80% specific for diagnosing cirrhosis. The hepatic venous pressure gradient measurement predicts the presence of cirrhosis in patients with liver disease. Therefore, when the diagnosis of cirrhosis is in question, an elevated hepatic venous pressure gradient can support the diagnosis.
Hepatic iron concentration has consistently been observed as being directly correlated with the r... more Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus (HCV). We therefore conducted a randomized, controlled trial comparing iron reduction by phlebotomy with iron reduction followed by retreatment with interferon in 96 patients with chronic hepatitis C who had previously not responded to a course of interferon. During the initial phase when all patients were undergoing phlebotomy, we found that serum alanine transaminase (ALT) activities decreased but by less than 50% from baseline in 67 patients (89%), decreased by more than 50% in 12 patients (13%) and became normal in 9 patients (9%) with no overall change in HCV-RNA levels. Subsequently no patient in either treatment group achieved a sustained virologic response. Improvements in necroinflammatory changes were noted in liver biopsy specimens in those patients receiving phlebotomy plus interferon (mean index 8.59 vs. 7.37, P &amp;amp;amp;amp;lt;. 05). A slight but not statistically significant decrease in histologic activity index was noted in those subjects treated by phlebotomy alone (mean index 8.4 vs. 7.75, P not significant). We conclude that, although prior phlebotomy therapy does not improve the rate of sustained response to interferon retreatment, it does result in less liver injury manifested by a decrease in serum transaminase activity and a slight improvement in liver histopathology.
Background: Abnormal hematological indices (HI) are common in cirrhosis from hepatitis C virus (H... more Background: Abnormal hematological indices (HI) are common in cirrhosis from hepatitis C virus (HCV). Eradication of HCV may ameliorate these abnormalities. The objectives of the current study were to assess whether HI improve with HCV eradication and whether they can predict prognosis in patients with cirrhosis during and after completion of antiviral therapy. Methods: A retrospective cohort study of 153 patients with HCV cirrhosis treated with Peg-interferon and ribavirin was conducted. The primary endpoint was improvement in HI after successful antiviral therapy. The secondary outcome was clinical decompensation during and after completion of antiviral therapy and association with HI. A repeated measures 2-way ANOVA was performed to compare means. Multivariate analysis was used to identify predictors of clinical decompensation. Results: One hundred fifty three patients met study criteria. The rate of sustained virological rate was 26%. Median follow-up was 55 months. Platelet and WBC counts improved with HCV eradication compared to those in whom treatment was unsuccessful (p < 0.05). On univariate analysis, the presence of thrombocytopenia was associated clinical decompensation prior to, on treatment and after completion of therapy. Thrombocytopenia (OR 14.8, p-value <0.001) after completing treatment predicted clinical decompensation when controlled for albumin, MELD and age in multivariate analysis at 6 months after completion of therapy. Conclusions: Platelet and leukocyte counts improve in patients with cirrhosis who respond to antiviral therapy against HCV. The presence of thrombocytopenia predicts decompensation on treatment and after completion of therapy.
Results from prospective controlled trials do not justify the use of either prophylactic shunt su... more Results from prospective controlled trials do not justify the use of either prophylactic shunt surgery or sclerotherapy for the prevention of initial variceal bleeding. Use of nonselective beta-adrenergic blockers has been shown to reduce significantly the risk of first variceal hemorrhage, but their effect on survival is marginal. Because only 25% to 40% of patients with cirrhosis and varices experience variceal bleeding, is it justified to place all patients with varices on beta-blocker therapy? The answer lies in the identification of a high-risk population (i.e., patients with large varices and endoscopic red color signs) and patients who can tolerate and will be compliant with therapy. The duration of therapy required is unknown and perhaps requires a lifetime commitment. Future research will involve the use of combinations of pharmacologic agents to reduce further portal pressure and perhaps the use of pharmacologic agents and sclerotherapy. The goal of a significant improveme...
This report describes a middle-aged female who received imipramine for 7 days, developed severe c... more This report describes a middle-aged female who received imipramine for 7 days, developed severe cholestatic jaundice with features similar to primary biliary cirrhosis, and then improved clinically over the next 12 mo. Biochemical and histologic abnormalities persisted over a 14-yr period of follow-up, though subsequent administration of haloperidol may have influenced the long-term course. High levels of circulating immune complexes were also found 14 yr later, which raises questions about the relationship of primary biliary cirrhosis to drug-induced liver injury. A review of the literature on imipramine- and phenothiazine-related hepatic injuries reveals multiple similarities, and this case provides further evidence for a common hepatic reaction to the two drugs.
Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of s... more Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis. Compare mortality in patients with cirrhosis on statins to those not on statins. A retrospective cohort study evaluated patients from 1988 to 2011 at Partners Healthcare Hospitals. The Partners Research Patient Data Registry identified patients with biopsy-proven cirrhosis on statins at biopsy and at least 3 months following. Controls were matched 1:2 by age, gender and Child-Pugh class. Decompensation was defined as ascites, jaundice/bilirubin &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2.5 mg/dL, and/or hepatic encephalopathy or variceal hemorrhage. Primary outcome was mortality. Secondary outcome was decompensation in baseline-compensated patients. Chi-square and two-way ANOVA testing compared groups. Cox proportional hazards models for mortality controlled for age, Child-Pugh class, diabetes, coronary artery disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Kaplan-Meier curves graphed mortality. Eighty-one statin users and 162 controls were included. Median follow-up: 36 months in statin users and 30 months in controls. 70.4% of patients were Child-Pugh A. Model for End-Stage Liver Disease (MELD), albumin, varices and beta-blocker use were not significantly different between groups. Statin users had lower mortality on multivariate analysis (HR 0.53, p = 0.01), and Child-Pugh A patients had longer survival on Kaplan-Meier analysis. Cox multivariate analysis for decompensation showed lower risk of decompensation with statins while increased decompensation with low albumin, high MELD score and beta-blocker use. In patients with cirrhosis, statin therapy is not associated with increased mortality and may delay decompensation.
Page 1. SESSION 4 Primary Prophylaxis for Variceal Bleeding Norman D. Grace, Juan Carlos Garcia-P... more Page 1. SESSION 4 Primary Prophylaxis for Variceal Bleeding Norman D. Grace, Juan Carlos Garcia-Pagan, Mario Angelico, Richard Moreau, Agustin Albillos, Michael Schepke, Thomas D. Boyer and Naga Chalasani INTRODUCTION ...
Liver biopsy is the gold standard for establishing cirrhosis, but may provide inadequate tissue f... more Liver biopsy is the gold standard for establishing cirrhosis, but may provide inadequate tissue for interpretation in some patients. The aim of this study was to determine whether the hepatic venous pressure gradient predicts the presence of cirrhosis. Patients with liver disease who had undergone hepatic venous pressure gradient measurements were identified. Clinical, laboratory, and hepatic venous pressure gradient data were collected and biopsies were staged for fibrosis. Univariable logistic regression was used to identify potential predictors of cirrhosis. Multivariable logistic regression was applied to determine adjusted odds ratios. Thirty-two patients were included. The hepatic venous pressure gradient was an independent predictor of cirrhosis. On multivariable analysis, the hepatic venous pressure gradient predicted cirrhosis, with an odds ratio of 1.46 (95% confidence interval 1.05-2.02, P=0.023). Using a cutoff of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=6.5 mm Hg, the hepatic venous pressure gradient was 86% sensitive and 80% specific for diagnosing cirrhosis. The hepatic venous pressure gradient measurement predicts the presence of cirrhosis in patients with liver disease. Therefore, when the diagnosis of cirrhosis is in question, an elevated hepatic venous pressure gradient can support the diagnosis.
Hepatic iron concentration has consistently been observed as being directly correlated with the r... more Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus (HCV). We therefore conducted a randomized, controlled trial comparing iron reduction by phlebotomy with iron reduction followed by retreatment with interferon in 96 patients with chronic hepatitis C who had previously not responded to a course of interferon. During the initial phase when all patients were undergoing phlebotomy, we found that serum alanine transaminase (ALT) activities decreased but by less than 50% from baseline in 67 patients (89%), decreased by more than 50% in 12 patients (13%) and became normal in 9 patients (9%) with no overall change in HCV-RNA levels. Subsequently no patient in either treatment group achieved a sustained virologic response. Improvements in necroinflammatory changes were noted in liver biopsy specimens in those patients receiving phlebotomy plus interferon (mean index 8.59 vs. 7.37, P &amp;amp;amp;amp;lt;. 05). A slight but not statistically significant decrease in histologic activity index was noted in those subjects treated by phlebotomy alone (mean index 8.4 vs. 7.75, P not significant). We conclude that, although prior phlebotomy therapy does not improve the rate of sustained response to interferon retreatment, it does result in less liver injury manifested by a decrease in serum transaminase activity and a slight improvement in liver histopathology.
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