Assessing the patient with a new diagnosis of Hepatitis C LAUREN MYERS MMSC, PA-C OREGON HEALTH & SCIENCE UNIVERSITY

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1 Assessing the patient with a new diagnosis of Hepatitis C LAUREN MYERS MMSC, PA-C OREGON HEALTH & SCIENCE UNIVERSITY

2 Disclosures Nothing to Disclose

3 Assessing the patient with a new diagnosis of Hepatitis C Interpreting HCV testing results Identify the key laboratory tests relevant to recently diagnosed patients Recognize the clinical features of HCV Discuss the pathogenesis of liver fibrosis and what may accelerate fibrosis progression

4 Diagnostic tests: Anti-HCV: Serologic testing to detect antibodies mounted in response to HCV infection A positive anti-hcv indicates exposure to HCV at some point but does not distinguish between current infection and resolved infection Not protective! Detected by serologic screening tests within 4-10 weeks of infection Present in >97% of persons within 6 months of exposure False positive testing may be present Centers for Disease Control and Prevention (CDC) cdc.gov/hepatitis/hcv.2017, Chung et al, AASLD-IDSA Guidelines, Hepatology 2015:62 (3)

5 Diagnostic tests: HCV RNA (Nucleic Acid Testing) Gold standard confirmatory testing following a positive anti-hcv ab test Can be detected in the blood within 2-3 weeks of infection Qualitative testing: detects presence of RNA, useful for dx of chronic HCV only Quantitative testing: detect titer of RNA and used for treatment purposes. Use of testing that detects 25 IU/mL or lower of HCV RNA is recommended Testing for HCV RNA should be used in those who are immunosuppressed (ie persons on chronic hemodialysis) or those who may have had expose within 6 months as anti-hcv may not be positive Testing for HCV RNA is also recommended in those who are anti-hcv positive with prior spontaneous clearance or prior treatment Centers for Disease Control and Prevention (CDC ) cdc.gov/hepatitis/hcv.2017, Chung et al, AASLD-IDSA Guidelines, Hepatology 2015:62 (3)

6 Centers for Disease Control and Prevention (CDC) cdc.gov/hepatitis/hcv.2017

7 Centers for Disease Control and Prevention (CDC) cdc.gov/hepatitis/hcv.2017

8 Acute infection of Hepatitis C Defined as patient who presents within 6 months of exposure to the virus Within the first 6 months of exposure there is 15-50% chance of spontaneous clearance of the virus May be present if: 1. Positive HCV RNA in the setting of a negative anti-hcv antibody 2. Presence of a positive anti-hcv antibody after a prior negative anti-hcv antibody (seroconversion) Suspected if a discrete exposure is known Suspected if acute rise in ALT or low (less than 104 IU/mL) or fluctuating HCV RNA levels AASLD-IDSA hcvguidelines.org 2017

9 Acute Infection of Hepatitis C Testing Algorithm- AASLD Guidelines accessed 6/2017

10 Acute infection of Hepatitis C Predictors of spontaneous clearance: Young age (below 40 at time of infection) Female Symptomatic infection (i.e. Jaundice, abdominal pain) No HIV-coinfection Not immunocompromised Difference in HCV genotypes (IL 28B) Kamal et al, Am J Gastroenterology 2008;103(5)

11 HCV infection is chronic, now what? Hepatitis C Genotyping There are seven* recognized genotypes based on phylogenetic & sequence analysis of virus Genotype 3 has been associated with increased risk of hepatic steatosis and hepatocellular carcinoma Effective DAA treatments for all genotypes *1 known case report of genotype 7 Messina et al. Hepatol,ogy 2015;61(1) Kanwal et al. Hepatology (1)

12 HCV infection is chronic, now what? Clinical manifestations of Hepatitis C Majority of patients are asymptomatic Symptoms range from mild (fatigue and joint pains, abdominal pain) to those of advanced liver disease (jaundice, ascites, variceal bleeding and hepatic encephalopathy, hepatocellular carcinoma) Extrahepatic manifestations of HCV Abnormal liver enzymes Progression of hepatic fibrosis AASLD-IDSA hcvguidelines.org 2017, Centers for Disease Control and Prevention (CDC) cdc.gov HCV 2017

13 Extrahepatic Manifestations of HCV Hematologic Mixed cryoglobulinemia Lymphoproliferative disorders Renal Membranoproliferative glomerulonephritis (MPGN)/proteinuria Dermatologic Porphyria Cutanea Tarda Leukocytoclastic vasculitis Lichen Planus Necrolytic Acral Erythema Diabetes Mellitus Autoimmune Autoantibodies Thyroid disease Autoimmune ITP Sjogren s Rheumatoid Arthritis Sarcoidosis Myasthenia gravis Ophthalmologic Disorders Neurologic Mononeuropathy multiplex Acute Inflammatory Syndromes Cerebral Vasculitis

14 Liver Enzymes in chronic HCV May be abnormal with chronic HCV infection Normal values ALT female less than 19 IU/L and male less than 30 IU/L Tend to fluctuate Serum ALT is released from liver tissue in proportion to the degree of hepatocellular damage and may be a marker for liver injury and disease progression However: In up to 24% of those with persistently normal ALT levels, there can be stage 1 fibrosis Serum AST levels are an important predictor of histological activity Ahmad et al. Virology Journal, (1): p53. Pradat et al. Hepatology, (4pt1)973-7

15 Liver Fibrosis Grading of portal/lobular necroinflammatory activity of chronic hepatitis A. Minimal activity, B. Mild activity, C. Moderate activity, D. Severe activity accessed 5/ accessed 5/2017

16 HCV Natural History Kemmer et al, Liver Int (10)

17 Liver Fibrosis Progression is influenced by a combination of environmental, host and viral factors The presence of fibrosis begets more fibrosis Fibrosis progression is not linear Liver fibrosis progression occurs more rapidly in Genotype 3 HCV infection The the level of HCV RNA does NOT correlate the stage of disease (either inflammation or fibrosis) Kanwal et al. Hepatology (1) , Feld et al. Hepatology (S1)S194-S206, Poynard et al. J Hep (5)

18 Factors influencing Liver Fibrosis Host Duration of infection Age at infection Gender (male) Toxins Alcohol consumption Tobacco/Cannabis use Iron Overload Feld et al. Hepatology (S1)S194-S206 Immunosuppression HIV co-infection Organ transplant Liver-related Factors HBV/HAV co-infection ALT elevation Fibrosis Metabolic Factors Steatosis Insulin Resistance

19 Adapted Poynard et al. Lancet :825-32

20 Liver Fibrosis and coffee? It has been suggested that coffee consumption has been associated with lower rates of disease progression in those with HCV-related liver disease (less steatosis, lower AST/ALT, lower AFP, higher albumin) An association was not found with black or green tea Outcome rates did decline with increasing coffee consumption Freedman et al. Hepatology (5)

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