SUBSTANCE USE DISORDERS ANDHEPATITIS C --- (SLIDE 1)
I. INTRODUCTION
A. Overview of this lecture -- (SLIDE 2)
1. Background
a. Effects of alcohol and drugs on the liver
b. Importance of hepatitis C virus (HCV)
2. Connection between alcohol/substance use disorders and hepatitis C
a. Epidemiology
i. Prevalence
(a) Alcohol/other substance use disorders in patients with HCV
(b) HCV in patients with alcohol and substance use disorders
b. Transmission Ð alcohol/substance use disorders and risk factors
foracquisition of HCV
c. Effects of alcohol/substance use on natural history of HCV
d. Effects of alcohol and other substance use on treatment of HCV
e. Implications for patient care
i. Prevention of HCV in patients with substance use disorders
ii. Optimizing health of patients with HCV and substance use disorders
iii. Antiviral treatment of HCV in patients with substance use disorders
B. The liver is important --- (SLIDE 3)
1. Largest organ
2. Complex functions
3. Maintains homeostasis and health of organism
C. Liver - basic physiology 1
1. Metabolism, maintains metabolic homeostasis
a. Carbohydrates
b. Fats
c. Proteins
d. Inactivation of polypeptide hormones, steroid hormones
e. Detoxification of vast majority of non-water soluble medications,
drugs,alcohol, other substances
2. Location for storage of:
a. Glycogen
b. Protein
c. Fats
d. Vitamins
3. Synthesizes:
a. Bile (necessary for digestion)
b. Cholesterol
c. Lecithin
d. Phospholipids
e. Plasma proteins
D. Liver - vulnerable to damage by drugs and toxins 1
1. Toxins include: alcohol, other substances of abuse
a. Direct toxic effects on liver
b. Indirect damage
i. Other systemic effects of substances
ii. Viral hepatitis
II. SUBSTANCE USE AND THE LIVER - HEPATOTOXICITY OF ALCOHOL AND
DRUGS
A. Direct toxic effects of alcohol --- (SLIDE 4)
1. Alcoholic liver disease
a. Causes may include: 2
i. Hypoxia
(a) Alcohol metabolism consumes oxygen
(b) Oxygen deprivation in area of central veins
ii. Inflammation
(a) Neutrophil infiltration into hepatocytes
(b) Alcohol metabolism produces mediators attracting neutrophils
iii. Autoimmune mediated injury
(a) Products of alcohol oxidation bind proteins producing antigens
(b) Antigens provoke cell-mediated and humoral immune response
againstcells containing these compounds
iv. Action of cytokines
(a) Increased levels of tumor necrosis factor and interleukin-6
withalcohol consumption
(b) These cytokines may cause liver injury
b. Severity of liver disease in heavy drinkers
i. Extreme individual variability re: vulnerability
ii. Factors that may be important:
(a) Genetics
(b) Gender
(c) Amount ingested
(d) Duration of heavy drinking 2,3
iii. Usual threshold dose for severe liver damage:
(a) 80 grams per day for 10+ years (standard drink = 10-12 grams of
alcohol); (Remember Ð this is highly variable)
(i) May be less in some individuals
(ii) Many heavy drinkers and individuals with alcohol use
disorders donot develop severe liver disease
(b) Significant percentage of people with alcoholic liver disease
(andcirrhosis) do not meet criteria for alcohol use disorder
(c) Amount of alcohol not type of beverage is determining factor; 3
c. Progression of alcohol-related changes in liver
i. Steatosis Ð fatty liver Ð may develop after single episode of
heavyalcohol use; does not predict progression to fibrosis or cirrhosis;
(a) Rarely diagnosed
(b) May be asymptomatic or mild tender hepatomegaly
(c) Liver function tests may be normal
ii. Alcoholic hepatitis Ð Mild cases common; severe cases rare but may
belethal
(a) Symptoms Ð fever, hepatomegaly, jaundice
(b) Elevations of transaminases, alkaline phosphatase, bilirubin
iii. Cirrhosis
(a) Similar clinical and laboratory features as noted in cirrhosis
fromother causes
(b) Increased risk of liver disease
(i) Associated with greater than 4-6 drinks per day for men; greater
than2 drinks per day for women
(ii) One study Ð very heavy drinkers (average > 10 drinks per day
for> 10 years) Ð risk of severe liver disease (cirrhosis and precirrhoticlesions) approximately 50%
B. Hepatotoxicity of drugs of abuse --- (SLIDE 5)
1. MDMA (3,4 methyldioxymethamphetamine) Ð ÒEcstasyÓ4,5,6
a. Fulminant hepatic failure reported
i. Can result in liver transplant and/or death
ii. May occur days to weeks after ingestion
b. Less severe cases - jaundice, increased liver function tests,hepatomegaly
c. Mechanism is unclear Ð possible explanations:
i. Hyperpyrexia
ii. Immune-mediated injury
2. Cocaine
a. Direct hepatic injury uncommon in humans Ð possible causes
ofhepatotoxicity in humans include: 7
i. Liver injury secondary to hyperthermia, hypoxia, hypotension
ii.
Hepatic necrosis from ischemia
3. Anabolic steroids 8,9
a. Cholestatic jaundice Ð common
i. Caused by large amount of drug stressing metabolic capacity of liver
ii. Side effect used by bodybuilders to titrate amount of drug they areusing
b. Hepatitis - ÒPeliosis hepatitisÓ
i. Blood filled cysts scattered throughout liver
ii. Rarely causes symptoms
c. Hepatic adenomas
i. Develop in 1-3% of users
ii. Rare symptoms
4. Phencyclidine (PCP) - liver toxicity associated with hyperthermia
(fewcases)10
C. Indirect damage11
1. Secondary to systemic effects of drugs and alcohol
a. Hypo and hyperthermia Ð e.g. PCP, cocaine
b. Shock
c. Ischemia Ð e.g. cocaine
2. Indirect damage to the liver from acquired illnesses Ð most common -viral
hepatitis
a. Hepatitis A
i. Transmitted via fecal-oral route
ii. Patients with substance use disorders at higher risk for acquiringthis
illness (lifestyle issues?)
b. Hepatitis B
i. Higher risk in intravenous drug users
ii. Associated with fulminant hepatic failure
iii. Chronic hepatitis in 5%
c. Hepatitis C
i. Transmitted via exposure to infected blood
ii. Individuals with substance use disorders more vulnerable
iii. Lecture will discuss in detail
III. OVERVIEW OF HEPATITIS C --- (SLIDE 6)
A. Importance Ð major public health issue
1. Major cause of liver disease
a. May cause serious liver disease and death
i. Cirrhosis, end-stage liver disease (decompensated cirrhosis)
ii. Hepatocellular carcinoma
b. Hepatitis C virus identified in 198912
c. Most cases of Ònon-A non-BÓ hepatitis are HCV12
d. Leading indication for liver transplantation in the US12
2. Epidemiologic data Ð prevalence in US and worldwide 12,13,14,15
a. 170 million worldwide
b. At least 4 million in US; 2.7 million with chronic infection
i. Overall prevalence approximately 2% in US (data excluded homeless
andincarcerated persons Ð rate may be higher)
ii. Prevalence higher in special populations
(a) Emergency medical technicians (~ 2.5%)
(b) Alcoholics (10%)
(c) Homeless (15-20%)
(d) Incarcerated persons (50%)
(e) IV drug users and hemophiliacs (70-90%)
iii. 38,000 new cases per year
c. ~ 10% have serious complications Ð (400,000 in US have serious
liverdisease)
d. 10-20,000 deaths/year
B. Hepatitis C virus16 --- (SLIDE 7)
1. Description
a. Small, enveloped, single-stranded RNA virus Ð Flaviviridae
family(related to yellow fever virus)
b. Mutates rapidly Ð obstacle to vaccine development Ð (none
currentlyavailable)
2. At least 6 genotypes; at least 50 subtypes
a. Genotype 1 most common in US
i. 70 -80% of cases in US
ii. 1b is the most common genotype
b. Genotype 2 and Genotype 3 (frequent in Indian subcontinent) Ð 20-30%
ofcases in US
c. Genotype 4 Ð most common genotype of Africa and Middle East
d. Genotype 5 Ð South Africa; Genotype 6 Ð Hong Kong and Southeast
Asia(these are rare)
3. No correlation between genotype and severity of disease
4. Re-infection may occur; previous infection with genotype/subtype
onlyconfers immunity to that specific genotype/subtype
C. Transmission of HCV --- (SLIDE 8)
1. Transmitted via exposure to infected blood
2. Risk factors for HCV transmission12,14,15
a. Blood transfusions prior to 1992
i. After 1992 Ð widespread testing available
ii. No reported cases of transmission by blood transfusion since 1994
b. Unsafe medical practices
i. Particularly in 3rd world countries
ii. Use and re-use of contaminated syringes, needles, other instruments
iii. Transfusion of contaminated blood, blood products
iv. Failure to use universal precautions
c. Occupational exposures Ð prevalence in health care workers higher
thangeneral population (up to 3-4x prevalence)
i. Needlestick injuries Ð risk about 1.8% with each exposure toHCVcontaminated needles
ii. Other exposures to infected blood
d. Intravenous drug use - sharing of needles contaminated with HCV
e. Intranasal drug use Ð theoretical exposure to blood from
contaminatedstraws17
f.
Tattoos Ð much controversy
i. Conflicting studies - different patient cohorts and differentmethodology
ii. ?difference between commercial tattoo parlors vs. homemade
tattoos18,19
iii. Use of contaminated needles
iv. Contaminated ink
g. High risk sexual practices: multiple sexual partners, sex with
HCV+partners, sexual practices resulting in disruption of mucosal
membranes ortrauma causing bleeding20
i. Sex Ð inefficient method of HCV transmission
ii. 18% with acute HCV reported sexual contact as only risk
factor(community study by CDC)
(a) 2/3 reported known HCV+ sexual partner
(b) 1/3 reported multiple partners
iii. Sexual transmission uncommon in long-term monogamous
relationships
iv. Increased risk seen with untreated sexually transmitted diseases;HIV;
h. Maternal transmission during childbirth Ð uncommon21
i. Rate = 4-7% when mother has active HCV infection and detectable
HCVviral RNA
ii. Risk increases with maternal HIV infection to up to 20% - maycorrelate
with higher levels of maternal HCV viral RNA
D. Natural history of HCV infection15,16,22,23
1. Virus replicates only in liver
2. Carried through bloodstream via neutrophils
3. Liver damage caused by immune attack on cells containing virus Ð virusdoes
not directly attack/damage hepatocytes
4. Acute HCV infection --- (SLIDE 9)
a. Approximately 2/3 asymptomatic
b. Symptoms develop 3-12 weeks after infection
i. Fever, weakness, anorexia, malaise, jaundice
ii. May be severe, rarely causes fulminant hepatic failure
c. Viral RNA detectable in serum within 1-2 weeks; antibody detectable
in97% of infected persons within 6 months
d. Some clear the virus after initial infection Ð Òearly viral clearanceÓ
Ðassociated with younger age, female gender, non-African-American
ethnicity;
e. 60-85% have chronic infection
i. Persistence of HCV viral RNA for at least 6 months after infection
ii. Exact prevalence of chronic infection unclear
5. Chronic HCV infection --- (SLIDE 10)
a. Signs and symptoms
i. Symptoms
(a) Generally none
(b) Intermittent fatigue
(i) Frequent complaint Ð unclear association with HCV infection
(ii) Nonspecific Ð except in patients with severe liver disease
ii. Physical examination Ð often normal
iii. Laboratory studies
(a) May be normal
(b) ALT (SGPT) > AST (SGOT) Ðthese enzymes range from normal
to 10xnormal in chronic HCV
(c) Other tests Ð bilirubin, albumin, prothrombin time - often normal
b. Consequences of chronic HCV
i. Progression highly variable
ii. Liver function tests normal in 30-40% with chronic infection
(a) Majority of this group Ð no active liver disease
(b) Small percentage Ð significant liver disease on biopsy
iii. 50% have mild to moderate disease; slowly progressive and/or stable
iv. Cirrhosis and end-stage liver disease (decompensated cirrhosis) - upto
15% over 20-30 years
v. Hepatocellular carcinoma Ð up to 5% of those with chronic infection
vi. Predictors of rapid progression of disease
(a) Older age at infection
(b) Male
(c) Immunosuppressed
(d) Co infection with HIV and/or HBV
(e) Heavy alcohol use
(f) Diabetes
c. Extrahepatic manifestations Ð develop in 1-2%; may occur in absence
ofsignificant liver disease
i. Cryoglobulinemia Ð most common Ð
(a) Cryoglobulins
(i) Immunoglobulins - precipitate at < 37 degrees C
(ii) Re-dissolve with warming
(iii) Associated with HCV and other conditions - exact
pathogenesisunclear
(b) Symptoms
(i) Skin rash
(ii) Joint and muscle aches
(iii) Renal disease
(iv) Neuropathy
ii. Other
(a) Glomerulonephritis
(b) Porphyria cutanea tarda1
(i) Acquired disorder of heme biosythesis
(ii) Photosensitivity is only major manifestation
(iii) Skin lesions Ð enhanced pigmentation, increased skin
fragility,skin trauma and fragility, vesicular and ulcerative
lesions, sclerodermatouschanges
IV. SUBSTANCE USE DISORDERS AND HCV --- (SLIDE 11)
A. What is the connection?
1. High prevalence of all forms of hepatitis in patients with alcohol
andsubstance use disorders
2. Prevalence of hepatitis C (HCV) in patients with alcohol and substanceuse
disorders
a. Alcohol use disorders Ð approximately 10%24
b. Substance use disorders Ð up to 90% in intravenous drug users (IVDUs)12
3. High prevalence of substance use disorders in patients with HCV
a. Several studies of VA patients Ð 60-80% with HCV had alcohol
and/orsubstance use disorders25,26,27
b. Comorbid HCV/alcohol/substance use is the rule
i. Must recognize to provide optimal treatment
ii. Implications for HCV prevention/treatment
4. Issues of importance - interaction between substance use disorders
andhepatitis C --- (SLIDE 12)
a. Transmission/risk factors
i. Acquisition
ii. Implications for prevention of hepatitis C
b. Natural history of illness Ð impact of comorbid substance use on
courseand outcome of hepatitis C
c. HCV treatment Ð effects of comorbid substance use on antiviral treatment
d. Implications for patient care Ð patients with substance use disordersand
HCV
i. Prevention
ii. Improving outcomes Ð preventing morbidity and mortality
iii. Antiviral treatment
B. Drug use and transmission of HCV --- (SLIDE 13)
1. Risk with IV, intranasal and other routes of use
a. Highest risk with intravenous use; other routes using
needles(intramuscular, subcutaneous)
b. Increased risk with intranasal use
c. Increased risk with other routes (smoking, ingestion)
i. ?Associated with other high risk behaviors Ð high risk sexualactivity,
tattoos
ii. ?Associated with concurrent heavy alcohol use
iii. ?Associated with decreased immune response Ð alcohol, marijuana
mayhave adverse effects on immune response
2. Risk with different drugs Ð route of use rather than drug of use appearsto be
most important factor
a. 60% new cases of HCV related to IV drug use28
b. Up to 50% of all cases in US related to IV drug use28
c. 70-90% of intravenous drug users are HCV+12
d. Intravenous drug users who share needles Ð up to 80% infected within
oneyear; close to 100% infected after 8 years28
C. Alcohol as a risk factor for HCV infection --- (SLIDE 14)
1. 10% of alcohol-dependent persons are HCV+ vs. 1.8% of generalpopulation;
increased prevalence even in absence of other risk factors24,29
a. Data from studies of patients presenting for general medical care andfor
detoxification
b. 30% of alcohol-dependent persons with liver disease are HCV+ 24
2. Proposed mechanisms
a. Enabling initial infection - decreased immune response - allows
survivaland persistence of virus after initial exposure30
b. Enhanced viral replication31,32
i. Associated with decreased immune response
ii. Decrease in replication of viral RNA with abstinence
c. Impaired ability of patient to clear virus after initial infectionÐlikely
immune related as well
D. Substance use disorders and natural history of HCV --- (SLIDE 15) ---alcohol use
and course of HCV infection--- (SLIDE 16)
1. Development of chronic HCV - increased viral replication anddissemination
throughout body after initial infection
2. Alcohol effects on inflammation, fibrosis, development of cirrhosis13,29Ð 42
a. Numerous studies Ð most in patients with heavy alcohol consumption
(atleast 3-4 drinks per day for >5 years)
b. Acceleration of liver damage
c. Greater hepatic inflammatory activity
d. Higher levels of HCV viral RNA
e. Increased fibrosis
f.
Increased risk of cirrhosis - odds ratios for development of cirrhosisin
HCV+ patients with heavy alcohol use vs. no alcohol use - patients
withheavy alcohol use and HCV Ð 10 times more likely to develop
cirrhosis --- (SLIDE17)
g. Increased risk of end stage liver disease and death
h. Most studies show increased inflammation, increased rates of fibrosisand
increased cirrhosis in patients with heavy alcohol use
3. Increased risk of hepatocellular carcinoma
E. Drug use and course of HCV infection --- (SLIDE 18)
1. Effects on natural history of HCV infection are unknown
2. Drugs of abuse may suppress the immune response and may
enhancehepatotoxicity
F. Cigarette smoking and course of HCV infection 43,44
1. Animal studies Ð nicotine may have deleterious effects on the liver
a. Steatosis (fatty liver), necrosis observed in rats
b. Aggravates hepatotoxic effects of other chemicals
2. Cigarette smokers with HCV
a. More severe hepatic inflammation
b. Increased rates of fibrosis
c. Effects of use of tobacco in other forms (cigars, pipes, etc) unknown
V. SUBSTANCE USE DISORDERS AND TREATMENT OF HCV --- (SLIDE 19)
A. Brief overview - treatment of HCV45,46,47 --- (SLIDE20)
1. Interferon
a. Protein synthesized by organism in response to viral infection
b. Natural antiviral activity
c. Standard interferon Ð given 3x per week via IM injection
d. ÒPegylatedÓ interferon Ð modified chemically by addition of
polyethyleneglycol
i. Prolongs half-life
ii. Given once weekly via IM injection
2. Ribavirin
a. Oral antiviral agent Ð given daily
b. Activity against broad range of viruses
c. Little effect against HCV when given alone
d. Increases response rate 2-3x when added to interferon
3. Current optimal treatment Ð pegylated interferon and ribavirin --- (SLIDE21)
a. Genotype 1 Ð 48 weeks of treatment
b. Genotypes 2 and 3 Ð 24 weeks of treatment
c. Compliance essential Ð patients must take 80% or more of doses
torespond
4. Treatment outcome
a. Successful treatment defined as: no detectable HCV viral RNA in serum
24weeks after course of treatment is complete (termed SVR or sustained
viralresponse)
b. > 90% of those with sustained viral response have no detectable
serumviral RNA in serum > 5 years
c. Successful treatment
i. Improvement seen on liver biopsy
ii. Normalization of liver function tests
d. Positive prognostic factors
i. Favorable genotype - differential response among genotypes
(a) Genotype 1 Ð 40-50% sustained viral response
(b) Genotypes 2,3 Ð 70-80% sustained viral response
ii. Absence of cirrhosis (on biopsy or clinical exam)
5. History of treatment approaches --- (SLIDE 22)
a. Data from large, often multicenter clinical trials
i. Criteria for inclusion Ð diagnosis of chronic HCV, increased
liverfunction tests, evidence of liver disease on biopsy
ii. Demographics of patients (in general, differs somewhat from trial
totrial)
(a) Average age Ð early 40s
(b) Male:Female = 2:1
(c) Most patients Caucasian
(d) >60% genotype 1
b. Initially interferon alone for 24 weeks Ð response rate = 6%
c. Interferon alone for 48 weeks Ð response rate = 16%
d. Interferon + ribavirin for 24 weeks Ð response rate = 33%
e. Interferon + ribavirin for 48 weeks Ð response rate = 45%
f.
Pegylated interferon (long acting preparation) + ribavirin for 48
weeksÐresponse rate = 55%
6. Toxicity of treatment --- (SLIDE 23)
a. 10-14% of patients discontinue treatment because of side effects
b. Physical side effects common
i. Flu-like symptoms Ð fever, malaise, nausea, vomiting in > 60%
ii. Bone marrow suppression ~ 25%
iii. Thyroid abnormalities
iv. Retinopathy, optic neuritis
v. Interstitial pulmonary fibrosis
vi. Cardiac, renal failure
vii. Autoimmune syndromes
c. Neuropsychiatric side effects Ð up to 40%
i. Depression Ð most common
ii. Anxiety, agitation, irritability
iii. Insomnia
iv. Cognitive difficulties
v. Psychosis Ð various diagnoses included - <1% of patients
(a) Mania
(b) Delirium
(c) Presence of psychotic symptoms without diagnosis
B. History Ð Treatment of HCV in patients with alcohol and other substanceuse
disorders 12 --- (SLIDE 24)
1. 1997 NIH Conference on Management of Hepatitis C
a. Excluded all active users of alcohol and drugs from antiviral treatmentof
HCV
b. 6 months abstinence required from alcohol/drugs prior to evaluation
forHCV treatment
c. Majority of patients with HCV excluded from treatment
(remembercomorbidity data)
2. 2002 NIH Conference on Management of Hepatitis C
a. Eliminated exclusionary criteria for antiviral treatment of HCV forusers of
alcohol and drugs
b. Recommended abstinence from alcohol and drugs for all patients prior
toHCV treatment
c. Recognized safe and effective treatment of HCV in patients with
alcoholand substance use disorders possible
i. Ongoing heavy alcohol use Ð contraindication to HCV treatment
(a) Defined as >80grams per day (6-7 drinks per day)
(b) Alcohol interferes with antiviral action of interferon
(c) Risk of acute alcoholic hepatitis
ii. Active substance use Ð not an absolute contraindication to
HCVtreatment Ð suggested considering patients on case-by-case basis
for antiviraltreatment
d. Recognized need to treat these patients
i. High prevalence of HCV
ii. Prevent spread of HCV
e. Co-management strategies recommended Ð concurrent treatment by
chemicaldependency programs and hepatology clinics
C. Alcohol - treatment of HCV in heavy users of alcohol 12,34 --(SLIDE 25)
1. Abstinence Ð strongly recommended during antiviral treatment for allpatients
a. Improvement in liver function tests Ð especially AST and ALT
b. Improvement in liver disease Ð seen on biopsy
c. Decrease in level of HCV viral RNA
d. Better response to antiviral treatment
2. Current treatment recommendations and concerns
a. Ongoing heavy alcohol use
i. Contraindication to antiviral treatment for HCV
ii. Concerns include: --- (SLIDE 26)
(a) Poor compliance
(b) Exacerbation of underlying psychiatric illness and interferoninducedneuropsychiatric disorders
(c) Alcohol interferes with antiviral actions of interferon48,49,50,51
(i) Patients drinking alcohol during antiviral treatment - response
tointerferon inversely correlated with level of alcohol intake
during antiviraltreatment
(ii) Patients with history of alcohol use who are abstinent
duringantiviral treatment
a. Response rates inversely correlate with previous level of
alcohol use
b. Decreased interferon response in patients with recent heavy
alcohol use
(d) Increased risk of acute alcoholic hepatitis during interferon rx
Ðseveral reported cases in the literature52
b. Patients with heavy alcohol use and alcohol use disorders
i. Abstinence required prior to initiation of antiviral treatment Ðchemical
dependency treatment encouraged
ii. Co-management (hepatology and chemical dependency
professionals)strongly encouraged
D. Drugs - Treatment of HCV in patients with ongoing substance use 53 -- (SLIDE
27)
1. Current treatment recommendations and concerns
a. Abstinence recommended, not required
b. Treat active drug users on a case-by-case basis
2. Interferon and ongoing drug use
a. Concerns Ð increased toxicity, decreased efficacy, adverse
druginteractions Ð no evidence in studies to date
b. Strongest predictor of treatment response Ð compliance with
antiviralregimen, not relapse or ongoing drug use
c. Interferon appears safe and effective in the few studies performed todate
d. Studies of active drug users and methadone patients
i. Interferon safe, effective, well-tolerated
3. Concerns and the evidence --- (SLIDE 28)
a. Treatment adherence Ð can patients with drug problems be compliant?
i. Programs specifically designed to treat medical conditions in drugusers
Ð rates of compliance comparable to general population
b. Exacerbation of psychiatric illness
i. Drug users Ð high incidence of comorbid psychiatric illness
ii. Drugs of abuse Ð cause/exacerbate most psychiatric symptoms
iii. No data to support this concern Ð anecdotal reports of some problems
c. Precipitation of relapse to drug use
i. Interferon side effects - similar to withdrawal states Ð inducecraving for
drugs to alleviate symptoms
ii. Self-injection with interferon may precipitate relapse into IV druguse
iii. Increased psychiatric symptoms
iv. No data Ð some anecdotal reports of problems
d. Re-infection with HCV with relapse to use of intravenous drugs
(a) 2 studies Ð examined re-infection with relapse to drug use54,55
(i) Appears to be low incidence
(ii) Patient education about safe injection practices can minimize
risk
4. Recommendations
a. Offer treatment on a case by case basis
b. Encourage chemical dependency treatment
c. Co-management strategies (hepatology and chemical
dependencyprofessionals) strongly encouraged Ð may enhance outcomes
E. Summary of treatment recommendations Ð patients with alcohol andsubstance
use disorders -- (SLIDE 29)
1. Patients with heavy alcohol use and alcohol use disorders
b. Abstinence strongly encouraged
c. Education, chemical dependency treatment and co-management
strategiesmay enhance outcomes
2. Other substance use disorders
b. Individualized approach Ð consider treatment on case-by-case basis
c. Recognize, manage risks Ð noncompliance, relapse,
psychiatriccomplications
d. Education, chemical dependency treatment, co-management
strategiesrecommended
VI. SUMMARY AND CONCLUSIONS -- (SLIDE 30)
A. Conclusions - implications for patient care -- (SLIDE 31)
1. Prevention
a. Primary
i. Education of patients with substance use disorders about HCV
ii. Needle exchange programs
iii. Chemical dependency treatment
b. Secondary
i. Screening high risk patients (substance users)
ii. Chemical dependency treatment
iii. More education Ð so they donÕt spread HCV
2. Decreasing morbidity and mortality from HCV
a. Education, chemical dependency treatment Ð decrease progression
tocirrhosis, hepatocellular carcinoma
b. Antiviral treatment
3. Decreasing prevalence of HCV in population with substance use
disordersmay decrease transmission of HCV in general population
4. Care of patients with HCV and substance use disorders
a. Historically excluded from HCV treatment
b. In need of HCV treatment
c. Can and should receive treatment for both HCV and substance use!
B. Summary Ð what we have discussed --- (SLIDE 32)
1. Importance of HCV Ð public health issue
a. Affects 4 million in United States
b. Serious liver disease in 400,000 patients
c. #1 indication for liver transplantation
d. 10-20,000 deaths/yr
e. 38,000 new cases/yr
2. HCV and substance use disorders
a. High prevalence of HCV in patients with alcohol and substance
usedisorders
b. High prevalence of substance use disorders in patients with HCV
3. Drugs, alcohol and HCV Ð what we know
a. Transmission/risk factors
i. Alcohol Ð risk factor for HCV because of effects on immune response
ii. Drug use Ð users of injected drugs high risk for HCV Ð exposure
toinfected blood
b. Natural History
i. Alcohol Ð known to accelerate serious liver damage from HCV
ii. Drugs Ð unknown effects on liver damage from HCV;
additivehepatotoxicity possible
c. Treatment of HCV
i. Alcohol
(a) Adversely affects treatment of HCV
(b) Abstinence necessary during antiviral treatment
ii. Drugs
(a) Interferon treatment of active drug users can be safe and effective
(b) Consider treatment on case by case basis
d. Implications for patient care
REFERENCES
1.
Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL
(eds):HarrisonÕs Principles of Internal Medicine, 15th Edition. New
York,McGraw-Hill, 2001
2.
Friedman SL: Pathogenesis and frequency of development of alcoholicliver
disease. UpToDate Online 11.3 2003; http://www.uptodate.com (accessed
12/20/2003)
3.
Lelbach WK: Cirrhosis in the alcoholic and its relation to the volume
ofalcohol abuse. Ann NY Acad Sci 1975; 252:85-105
4.
Jones AL, Simpson KJ: Review article: mechanisms and management
ofhepatotoxicity in ecstasy (MDMA) and amphetamine intoxications.
AlimentPharmacol Ther 1999; 13:129-133
5.
Henry JA, Jeffreys KJ: Toxicity and deaths from3,4methylenedioxymethamphetamine (ÒecstasyÓ). Lancet 1992; 340:384-387
6.
Andreu V, Mas A, Bruguera M, Salmeron JM, Moreno V, Nogue S, Rodes
J:Ecstasy: a common cause of severe acute hepatoxicity. Journal of
Hepatology1998; 29:394-397
7.
Selim K, Kaplowitz N: Hepatoxicity of psychotropic drugs.
Hepatology1999; 29:347-351
8.
Lukas SE: The pharmacology of steroids, in Principles of
AddictionMedicine. Edited by Graham AW, Schultz TK, Mayo-Smith MF,
Ries RK, Wilford BB.Chevy Chase, American Society of Addiction
Medicine, 2003, pp 305-321
9.
Stimac D, Milic S, Dintinjana RD, Kovac D, Ristic S:
Androgenic/anabolicsteroid-induced toxic hepatitis. Journal of Clinical
Gastroenterology 2002;35:350-352
10.
Armen R, Kanel G, Reynolds T: Phencyclidine induced
malignanthyperthermia causing submassive liver necrosis. American Journal
of Medicine1984; 77:167-172
11.
Graham AW, Schultz TK, Mayo-Smith MF, Ries RK, Wilford BB
(eds):Principles of Addiction Medicine. Chevy Chase, American Society of
AddictionMedicine, 2003
12.
Seeff LB, Hoofnagle JH: National Institutes of Health
consensusdevelopment conference: management of hepatitis C: 2002.
Hepatology 2002;36:S1-S20
13.
Kim WR: The burden of hepatitis C in the United States. Hepatology2002;
36:S30-S34
14.
Alter MJ, Kruszon-Moran D, Nainan OV, MCQuillan GM, Gao F, Moyer
LA,Kaslow RA, Margolis HS: The prevalence of hepatitis C virus infection in
theUnited States, 1988-1994. New England Journal of Medicine 1999;
341:556-562
15.
Marsano LS: Hepatitis. Primary Care Clinics in office practice 2003;30:81107
16.
Hoofnagle JH: Course and outcome of hepatitis C. Hepatology 2002;36:S21S29
17.
Conroy-Cantilena C, VanRaden M, Gibble J et al.: Routes of
infection,viremia and liver disease in blood donors found to have hepatitis C
virusinfection. New England Journal of Medicine 1996; 334:1691-1696
18.
Alter MJ: Prevention of spread of hepatitis C. Hepatology 2002; 36:S93-S98
19.
Haley RW, Fischer RP: Commercial tattooing as a potentially
importantsource of hepatitis C infection: clinical epidemiology of 626
consecutivepatients unaware of their hepatitis C serologic status. Medicine
2001;80:134-151
20.
Terrault NA: Sexual activity as a risk factor for hepatitis C. Hepatology
2002; 36:S99-S105
21.
Roberts EA, Yeung L: Maternal-infant transmission of hepatitis C
virusinfection. Hepatology 2002; 36:S106-S113
22.
Seeff LB: Natural history of chronic hepatitis C. Hepatology 2002; 36:S35S46
23.
Thomas DL, Astemborski J, Rai RM, et al.: The natural history ofhepatitis C
virus infection. JAMA 2000; 284:450-456
24.
Schiff ER: Hepatitis C and alcohol. Hepatology 1997; 26:39S-42S
25.
El-Serag H, Kunik M, Richardson P, Rabeneck L: Psychiatric
disordersamong veterans with hepatitis C infection. Gastroenterology 2002;
123:476-482
26.
Lehman LL, Cheung RC: Depression, anxiety, post-traumatic stress
andalcohol-related problems among veterans with chronic hepatitis C.
AmericanJournal of Gastroenterology 2002; 97:2640-2646
27.
Straits-Troster KA, Sloan KL, Dominitz JA: Psychiatric and substanceuse
disorder comorbidity with hepatitis C. Psychiatric Annals 2003; 33:362-366
28.
Davis GL, Rodrigue JR: Treatment of chronic hepatitis C in active drugusers.
New England Journal of Medicine 2001; 345:215-217
29.
Schiff ER: The alcoholic patient with hepatitis C virus infection. Am
JMedicine 1999; 107:95-99
30.
Leiber CS: Alcohol and hepatitis C. Alcohol Research and Health
2001;25:245-254
31.
Pessione F, Degos F, Marcellin P, et al.: Effect of alcohol consumptionon
serum hepatitis C virus RNA and histological lesions in chronic hepatitis C.
Hepatology 1998; 27:1717-1722
32.
Oshita M, Hayashi N, Kasahara A, et al.: Increased serum hepatitis Cvirus
RNA levels among alcoholic patients with chronic hepatitis C.
Hepatology1994; 20:1115-1120
33.
Regev A, Jeffers LJ: Hepatitis C and alcohol. Alcohol Clin Exp Res
1999;23:1543-1551
34.
Peters MG, Terrault NA: Alcohol use and hepatitis C. Hepatology 2002;
36:S220-S225
35.
Wiley TE, McCarthy M, Breidi L, et al.: Impact of alcohol on thehistological
and clinical progression of hepatitis C infection. Hepatology 1998; 28:805809
36.
Tanaka T, Yabusako T, Yamashita T, et al.: Contribution of hepatitis Cvirus
to the progression of alcoholic liver disease. Alcohol Clin Exp Res
2000;24:112S-116S
37.
Ostapowicz G, Watson KJR, Locarnini S, et al.: Role of alcohol in
theprogression of liver disease caused by hepatitis C virus infection.
Hepatology1998; 27:1731-1735
38.
Loguercio C, Di Pierro M, Marino MPD, et al.: Drinking habits ofsubjects
with hepatitis C virus-related chronic liver disease. Alcohol andAlcoholism
2000; 35:296-301
39.
Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosisprogression
in patients with chronic hepatitis C. Lancet 1997; 349:825-832
40.
Cromie SL, Jenkins PJ, Bowden DS, Dudley FJ: Chronic hepatitis C:effect of
alcohol on hepatic activity and viral titre. J Hepatol 1996; 25:821-826
41.
Bellentani S, Pozzato G, Saccoccio G, et al.: Clinical course and riskfactors
of hepatitis C related liver disease in the general population: reportfrom the
Dionysos study. Gut 1999; 44:874-880
42.
Noda K, Yoshihara H, Suzuki K, et al.: Progression of type C
chronichepatitis to liver cirrhosis and hepatocellular carcinoma. Alcohol Clin
ExpRes 1996; 20:95A-100A
43.
Hezode C, Lonjon I, Roudot-Thoraval F, et al.: Impact of smoking
onhistological liver lesions in chronic hepatitis C. Gut 2003; 52:126-129
44.
Pessione F, Ramond M, Njapoum C, et al.: Cigarette smoking and
hepaticlesions in patients with chronic hepatitis C. Hepatology 2001; 34:121125
45.
Lindsay KL: Introduction to therapy of hepatitis C. Hepatology
2002;36:S114-S120
46.
Bisceglie AM, Hoofnagle JH: Optimal therapy of hepatitis C.
Hepatology2002; 36:S121-S127
47.
Fried MW, Shiffman ML, Reddy K et al.: Peginterferon alfa-2a plusribavirin
for chronic hepatitis C infection. New England Journal of Medicine2002;
347:975-982
48.
Ono K, Sata M, Murashima S, et al.: Biological responses toadministered
interferon in alcoholics. Alcohol Clin Exp Res 1996; 20:1560-1563
49.
Okazaki T, Yoshihara H, Suzuki K, et al.: Efficacy of interferon therapyin
patients with chronic hepatitis C. Comparison between non-drinkers
anddrinkers. Scand J Gastroenterol 1994;29:1039-1043
50.
Ohnishi K, Matsuo S, Matsutani K, et al.: Interferon therapy forchronic
hepatitis C in habitual drinkers: comparison with chronic hepatitis Cin
infrequent drinkers. Am J Gastroenterol 1996; 91:1374-1379
51.
Tabone M, Sidoli L, Laudi C, et al.: Alcohol abstinence does not offsetthe
strong negative effect of lifetime alcohol consumption on the outcome
ofinterferon therapy. J Viral Hepat 2002;9:288-294
52.
Zylberberg H, Fontaine H, Thepot V, et al.: Triggering of acutealcoholic
hepatitis by α-interferon therapy. J Hepatol 1999; 30:722-725
53.
Edlin B: Prevention and treatment of hepatitis C in injection drugusers.
Hepatology 2002; 36:S210-S219
54.
Sylvestre DL: Treating hepatitis C in methadone maintenance patients:an
interim analysis. Drug Alcohol Depend 2002; 67:117-123
55.
Backmund M, Meyer M, Von Zielonka M, Eichenlaub D: Treatment
ofhepatitis C infection in injection drug users. Hepatology 2001; 34:188-193