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DISCLOSURES This activity is jointly provided by Northwest Portland Area Indian Health Board and Cardea Cardea Services is approved as a provider of continuing nursing education by Montana Nurses Association, an accredited approver with distinction by the American Nurses Credentialing Center s Commission on Accreditation. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Institute for Medical Quality/California Medical Association (IMQ/CMA) through the joint providership of Cardea and Northwest Portland Area Indian Health Board. Cardea is accredited by the IMQ/CMA to provide continuing medical education for physicians. Cardea designates this live web-based training for a maximum of 1 AMA PRA Category 1 Credit(s) TM. Physicians should claim credit commensurate with the extent of their participation in the activity.

DISCLOSURES COMPLETING THIS ACTIVITY Upon successful completion of this activity 1 contact hour will be awarded Successful completion of this continuing education activity includes the following: Attending the entire CE activity; Completing the online evaluation; Submitting an online CE request. Your certificate will be sent via email If you have any questions about this CE activity, contact Michelle Daugherty at mdaugherty@cardeaservices.org or (206) 447-9538

CONFLICT OF INTEREST Paulina Deming is on an advisory committee for Gilead. None of the other planners or presenters of this CE activity have any relevant financial relationships with any commercial entities pertaining to this activity.

Acknowledgement This presentation is funded in part by: The Indian Health Service HIV Program and The Secretary s Minority AIDS Initiative Fund

HCV ECHO WESTERN STATES Liver Fibrosis Staging Paulina Deming, PharmD, PhC Associate Professor of Pharmacy-College of Pharmacy Project ECHO University of New Mexico Health Sciences Center March 28, 2018 Original presentation by: Date prepared:

OBJECTIVES 1. Describe the stages of hepatitis C related liver disease; 2. Identify non-invasive liver fibrosis staging methods

Why is it Important to Stage a Patient s Level of Liver Disease? Patients with cirrhosis may require a longer duration of HCV treatment and/or addition of ribavirin Patients with cirrhosis require additional evaluation and follow up care Endoscopy for evaluation of varices On-going (and indefinite) surveillance for hepatocellular carcinoma

Hepatitis C: Progression of Disease Normal Liver Time Chronic Hepatitis 20-25 years 25-30 years HCV Infection Cirrhosis HCC ESLD Death

Laboratories for Recognizing Fibrosis/Cirrhosis Alanine aminotransferase (ALT), aspartate aminotransferase (AST) Recognize level of inflammation and liver injury Serum albumin, direct bilirubin, international normalized ratio (INR) Assess hepatic synthetic function Complete blood count with differential Identify changes consistent with cirrhosis

Why is the CBC Important to Understand Liver Disease Severity? Anemia Can indicate complications of cirrhosis Sudden decline in hemoglobin concerning for bleeding Trends in declining hemoglobin concerning for slow bleeding Thrombocytopenia (<150 thousand) Due to portal hypertension caused by cirrhosis Portal hypertension causes: Platelets to become stuck in spleen More platelets damaged/destroyed Neutropenia Cirrhosis can cause bone marrow suppression

Abnormalities in Hepatic Panel Elevations in AST or ALT useful for measuring liver cell injury What is normal AST or ALT? 40 IU/mL Studies suggest this is too high and normal should be lower and different for men vs. women Healthy ALT is <30 IU/mL for men and <19 IU/mL for women Elevations in conjugated bilirubin suggest liver disease Loss of liver s ability to synthesize (lack of synthetic function) can be seen with: Low serum albumin Prolonged prothrombin time (elevated INR) Important to look at trends in labs over time

Findings Suggestive of Advanced Fibrosis/ Cirrhosis Presence or history of ascites or esophageal varices Low platelet count (<150,000 mm 3 ) APRI > 1.0 FIB-4 > 3.25 Fibrosure > 0.72 Imaging with evidence of cirrhosis (nodular contour of liver or evidence of portal hypertension) Liver biopsy with F3 or F4 fibrosis Transient elastography consistent with advanced fibrosis/cirrhosis

https://www.hepatitisc.uw.edu/page/clinical-calculators/apri Use an upper limit of normal of 40

https://www.hepatitisc.uw.edu/page/clinical-calculators/fib-4

Child-Pugh Classification of Cirrhosis for Drug Dosing 1 Point 2 Points 3 Points Encephalopathy None Moderate Severe Ascites Absent Mild- Moderate Severe/ Refractory Bilirubin (mg/dl) < 2 2-3 > 3 Albumin (g/dl) > 3.5 2.8-3.5 < 2.8 INR (PT Prolongation sec over control) <1.7 (0-4) 1.7-2.3 4-6 >2.3 (>6)

Child-Pugh Interpretation of Hepatic Function in a Patient with Cirrhosis C-P Score (Class) Liver Function 5-6 (A) Mild Dysfunction 7-9 (B) > 9 (C) Moderate Dysfunction Moderate dose reduction (~25%) for drugs that are mostly hepatically metabolized Severe Dysfunction Significant dose reduction (~50%) for drugs that are mostly hepatically metabolized Note: Child Pugh Score is calculated only for patients with cirrhosis

Liver Biopsy is Gold Standard but Liver biopsy is not reliable gold standard Sampling error leads to misinterpretation in 10-15% of cases Can miss the diagnosis of cirrhosis Invasive procedure with complications Expensive Poor patient acceptance Interpretation has significant inter observer variability Seeff LB, et al. Clin Gastroenterol Hepatol. 2010;8:877 883. The French METAVIR Cooperative Study Group. Hepatology. 1994;20:15-20

Natural History of Chronic Liver Disease Chronic liver disease Compensated cirrhosis Decompensated cirrhosis Death Development of complications: Variceal hemorrhage Ascites Encephalopathy Jaundice

Probability of Survival Patients with Cirrhosis Decompensation Shortens Survival 100 80 All patients with cirrhosis 60 40 Median survival~ 9 years 20 Decompensated cirrhosis Median survival~ 1.6 years 0 0 20 40 60 80 100 120 140 160 180 Months Source: Ginés P, et al. Hepatology 1987; 7:122-8.

Summary Important to recognize cirrhosis for medical management of HCV and for management of complications associated with chronic liver disease Advanced fibrosis/cirrhosis can be identified by Minimally invasive tests including laboratories Scoring systems utilizing laboratories Imaging Transient elastography Role of biopsy diminished in identifying cirrhosis

HCV ECHO WESTERN STATES End of Presentation Questions?