SUBSTANCE USE DISORDERS AND HEPATITIS C Marian Fireman, M.D. Oregon Health and Science University Portland VA Medical Center Portland, Oregon 11/7/2015 Copyright – Alcohol Medical Scholars Program 2004
Download ReportTranscript SUBSTANCE USE DISORDERS AND HEPATITIS C Marian Fireman, M.D. Oregon Health and Science University Portland VA Medical Center Portland, Oregon 11/7/2015 Copyright – Alcohol Medical Scholars Program 2004
SUBSTANCE USE DISORDERS AND HEPATITIS C
4/30/2020
Marian Fireman, M.D.
Oregon Health and Science University Portland VA Medical Center Portland, Oregon
Copyright – Alcohol Medical Scholars Program 2004 1
OVERVIEW
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Background
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Effects of alcohol/drugs on liver Importance of hepatitis C (HCV)
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Substance use disorders and HCV
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Epidemiology Transmission Natural history
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Treatment
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Implications for patient care
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THE LIVER
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Complex functions
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Maintains homeostasis and health Metabolism/storage/synthesis Vulnerability
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Direct toxic effects of alcohol/drugs Indirect damage
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ALCOHOLIC LIVER DISEASE
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Multiple theories Vulnerability – variable
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Serious liver disease - > 8 drinks/d > 10 years Steatosis – “fatty liver”
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Rarely diagnosed, generally asymptomatic Hepatitis
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Fever, hepatomegaly, jaundice, elevated liver function tests Cirrhosis
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HEPATOTOXICITY OF DRUGS
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Direct toxic effects
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Ecstasy - fulminant hepatic failure Anabolic steroids - cholestatic jaundice, hepatic adenomas Indirect liver damage
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Systemic effects – hypo/hyperthermia, ischemia, necrosis Viral hepatitis – types A, B,C
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IMPORTANCE OF HCV
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Causes serious liver disease #1 indication for liver transplant Epidemiology
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170 million infected worldwide 4 million infected in US (2%) 10% serious complications 10-20,000 deaths/yr
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HEPATITIS C
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Small RNA virus Mutates rapidly > 6 genotypes Multiple subtypes Reinfection occurs
Suggest downloading and inserting picture of hepatitis C virus in this space 4/30/2020 Copyright – Alcohol Medical Scholars Program 2004 7
HCV TRANSMISSION
UNKNOWN OTHER OCCUPATIONAL TRANSFUSION IV DRUG USE SEXUAL
4/30/2020 Data adapted from Centers for Disease Control Copyright – Alcohol Medical Scholars Program 2004 8
ACUTE HCV INFECTION
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2/3 asymptomatic Symptoms – 3-12 wks post-infection Antibody present within 6 months 15+% clear HCV virus
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Younger, female patients
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Up to 85% develop chronic infection
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CHRONIC HCV INFECTION
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No symptoms Physical exam, labs often normal Liver disease - progression variable
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Hepatic inflammation Fibrosis Cirrhosis Hepatocellular carcinoma
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SUBSTANCE USE DISORDERS AND HCV
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Comorbidity is the rule!
Prevalence of HCV in substance use disorders (SUDs)
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Alcohol – 10% Other SUDs - up to 90% Prevalence of SUDs in HCV
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60 to 80%
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SUBSTANCE USE DISORDERS AND HCV
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Substance use disorders and HCV
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Transmission Natural history Treatment Implications for patient care
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DRUG USE AND TRANSMISSION OF HCV
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Route of use – most important factor
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Needle use - highest risk
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Intranasal use – sharing straws New cases – 60% drug use Up to 90% IV drug users HCV+ IVDUs who share needles
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~80% infected within first year
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ETOH - RISK FACTOR FOR HCV INFECTION?
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Increased prevalence of HCV
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10% ETOH-dependent are HCV+
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~ 5x general population Increased even in absence of other risk factors Proposed mechanisms
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Decreased immune response Enhanced viral replication
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SUBSTANCE USE DISORDERS AND HCV
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Substance use disorders and HCV
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Transmission Natural history Treatment Implications for patient care
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ETOH AND NATURAL HISTORY OF HCV
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Increased risk of chronic HCV ETOH and HCV - liver damage
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Greater hepatic inflammatory activity Higher levels of HCV viral RNA Increased fibrosis Increased risk of cirrhosis Increased risk of hepatocellular carcinoma
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RISK OF DEVELOPMENT OF CIRRHOSIS
160 140 120 100 80 60 40 20 0 147 15 9 1 HCV - HCV+ HCV HCV+ NO ETOH HEAVY ETOH
Sasaki, personal communication 4/30/2020 Copyright – Alcohol Medical Scholars Program 2004 17
DRUG USE - NATURAL HISTORY OF HCV
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Effects poorly understood
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HCV viral RNA Progression of liver disease Drugs may be hepatotoxic Cigarette smoking and HCV
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Nicotine – possible hepatotoxicity More severe inflammation Increased fibrosis
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SUBSTANCE USE DISORDERS AND HCV
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Substance use disorders and HCV
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Transmission Natural history Treatment Implications for patient care
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SUBSTANCE USE DISORDERS AND TREATMENT OF HCV
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Overview – current treatment
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Interferon
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Protein synthesized by organism Natural antiviral activity Pegylation – allows 1x/wk injection
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Ribavirin
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Oral antiviral agent Little effect vs. HCV alone Increases response to interferon 2-3x
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TREATMENT OF HCV
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Current optimal treatment
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Pegylated interferon plus ribavirin Treatment outcome
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Definition of SVR Successful treatment
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Improvement of liver disease Normalization of liver function tests
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Prognostic factors
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TREATMENT OF HCV
60% 50% 40% 30% 20% 10% 0% 6% 16% 33% IFN-24 wks IFN-48 wks IFN+R 24wks
Adapted from VA Hepatitis C Resource Centers 4/30/2020
45% IFN+R 48wks
Copyright – Alcohol Medical Scholars Program 2004
55% PEG IFN+R -48 wks
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SIDE EFFECTS
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~15% discontinue treatment Physical - > 60%
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Flu-like symptoms Neuropsychiatric – up to 40%
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Depression – most common Anxiety, agitation, irritability Insomnia Cognitive difficulties Psychosis
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HISTORY – HCV TREATMENT AND SUDS
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1997 recommendations
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6 months abstinence required Majority of patients excluded from treatment 2002 recommendations
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Eliminated exclusionary criteria
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Recommended abstinence Recognized need to treat these patients Seeff, Hoofnagle 2002
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ALCOHOL AND HCV TREATMENT
Abstinence – strongly recommended
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Improved liver function tests
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Improvement in liver disease Decreased HCV-RNA Better response to antiviral treatment Ongoing heavy alcohol use (>80 g/day)
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Contraindication to antiviral treatment Ohnishi 1996, Okazaki 1994, Pessione 1998, Peters 2002
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ALCOHOL AND HCV TREATMENT
Concerns with heavy ETOH use
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Poor compliance Exacerbation of neuropsychiatric disorders
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Poorer response to antiviral treatment Acute alcoholic hepatitis Other recommendations
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Alcohol rehabilitation Co-management strategies
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SUBSTANCE USE AND HCV TREATMENT
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Abstinence
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Recommended not required Treat on case by case basis IFN and ongoing drug use
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No reports of adverse interactions No reports of decreased efficacy Compliance (not drug use) predicts treatment response Edlin 2002, Sylvestre 2002, Backmund 2001
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CONCERNS - SUBSTANCE USE AND HCV TREATMENT
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Treatment adherence
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Special programs – good compliance Exacerbation of psychiatric illness
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Anecdotes, no data Relapse to drug use
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Craving, need for self injection Anecdotes - no data Re-infection
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2 studies - low incidence
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Need for patient education Edlin 2002
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CURRENT TREATMENT RECOMMENDATIONS
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Alcohol use
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Abstinence recommended
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Heavy use - contraindication
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Education, alcohol rehabilitation Co-management strategies Substance use
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Case by case basis Abstinence recommended Recognize and manage risks Co-management strategies
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SUBSTANCE USE DISORDERS AND HCV
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Substance use disorders and HCV
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Transmission Natural history Treatment Implications for patient care
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IMPLICATIONS FOR PATIENT CARE
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Prevention Decreasing morbidity and mortality Decreasing transmission of HCV Treatment
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Co-management strategies needed
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Safe and effective treatment possible
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SUMMARY
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Effects of alcohol and drugs on liver Importance of HCV HCV and substance use disorders Drugs, alcohol and HCV
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Transmission Natural history Treatment Implications for patient care
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