Fibrosis[1]

Liver Cirrhosis Diana Alcantara-Payawal, MD, MSc, FPCP, FPSG, FPSDE

CIRRHOSIS Anatomical: Presence of nodules of hepatocytes separated by fibrous septa. Micronodular Macronodular Incomplete Septal Cirrhosis with massive necrosis

Pathophysiology of Cirrhosis: Role of Endothelium-Derived Nitric Oxide ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Iwakiri Y, Sessa WC. AASLD 2001

Pathophysiology of Cirrhosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Didier Lubrec MD, AASLD, 2001 Fibrosis

Evolution of Cirrhosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Stages of Cirrhosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Jensen Dennis. AASLD. 2001

Liver Disease Severity Scales in Decompensated HBV Cirrhosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Robert J. Fontana, M.D. Semin Liver Dis. 2003

Decompensated Cirrhosis ,[object Object],[object Object],[object Object],[object Object],[object Object]

Agents Used for Hepatic Fibrosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Poynard T et al, Evid-based Gastro Hepato, 1999

Significance of Variceal bleeding ,[object Object],[object Object],[object Object],[object Object],[object Object],National Institutes of Health (NIH) consensus conference October 2003

Portal pressure Formation of varices Dilatation of varices Variceal Rupture Hepatic Resistance Portal Blood Flow Dilatation of pre existing vessels Repeated increase in portal pressure due to meals, ethanol, exercise, increase intrabdominal pressure Angiogenic factors Varices present in 40% at diagnosis 6% yearly incidence Small to large varices : 12% yearly Incidence of first bleeding: Large varices: 30% at 2 years Small varices: 10% at 2 years

Ascites ,[object Object],[object Object],[object Object],[object Object],[object Object]

[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Ascites (SAAG) >1.1 g/dl Portal hypertension Cardiac causes CHF constrictive pericarditis Budd Chiarri Multifactorial Nephrotic syndrome < 1.1 g/dl Malignancy Tuberculosis Chylous ascites Pancreatic Multifactorial

Stepwise approach to the treatment of cirrhotic ascites Sodium restriction #1 + spirinolactone #1 + #2 + loop diuretic 10-20% >50% >90% Success rate LaBrecque Douglas MD, AASLD 2001

Treatment of uncomplicated ascites ,[object Object],[object Object],[object Object],Poynard T et al, Evid-based Gastro Hepato, 1999 NIH Consensus conference, October 2003 Practice Guidelines Runyon BA. Hepatology 2004 Mar

Treatment of hepatorenal syndrome ,[object Object],[object Object],[object Object],Poynard T et al, Evid-based Gastro Hepato, 1999 NIH Consensus conference, October 2003 Practice Guidelines Runyon BA. Hepatology 2004 Mar

Treatment of hepatorenal syndrome ,[object Object],[object Object],[object Object],Poynard T et al, Evid-based Gastro Hepato, 1990 NIH Consensus conference, October 2003 Practice Guidelines Runyon BA. Hepatology 2004 Mar

Treatment of hepatorenal syndrome ,[object Object],[object Object],[object Object],[object Object],[object Object],Poynard T et al, Evid-based Gastro Hepato, 1999 NIH Consensus conference, October 2003

Hepatic Encephalopathy Ammonia Synergistic Toxins GABA Endogenous Benzodiazepines Theories Blei AT. AASLD 2001

[object Object],[object Object],Pathophysiology of HE WCOG/AGA PRACTICE GUIDELINES. Hepatic Encephalopathy. 2001

Ammonia neurotoxicity hypothesis Described about a century ago Ammonia levels elevated in patients with cirrhosis but have no relation to severity of HE. Levels high due to shunting and decrease peripheral utilization of ammonia by muscle due to wasting. Ammonia affects brain function by altering the blood-brain barrier, reduced astrocyte uptake of glutamate altered cerebral metabolism

[object Object],[object Object],[object Object],[object Object],Clinical Subtypes (WCOG Consensus terminology) WCOG/AGA PRACTICE GUIDELINES. Hepatic Encephalopathy. 2001

Staging of HE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Andres T. Blei et al. The ACG Practice Guidelines, 2001

HE Grade 0 HE Grade 1 Weissenborn et al., J Hepatol 1998; 28: 646-653. NCT in Grade 0 to Grade I

Treatment of Hepatic Encephalopathy ,[object Object],[object Object],[object Object],[object Object],[object Object],Poynard T et al, Evid-based Gastro Hepato, 1999 NIH Consensus conference, October 2003 Andres T. Blei et al. The ACG Practice Guidelines, 2001

Fibrosis[1]

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Fibrosis[1]