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 – alcohol/substance use disorders and risk factors for acquisition 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



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 against cells containing these compounds

iv. Action of cytokines

(a) Increased levels of tumor necrosis factor and interleukin-6 with alcohol 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 – this is highly variable)

(i) May be less in some individuals

(ii) Many heavy drinkers and individuals with alcohol use disorders do not develop severe liver disease

(b) Significant percentage of people with alcoholic liver disease (and cirrhosis) 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 – fatty liver – may develop after single episode of heavy alcohol 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 – Mild cases common; severe cases rare but may be lethal

(a) Symptoms – fever, hepatomegaly, jaundice

(b) Elevations of transaminases, alkaline phosphatase, bilirubin

iii. Cirrhosis

(a) Similar clinical and laboratory features as noted in cirrhosis from other causes

(b) Increased risk of liver disease

(i) Associated with greater than 4-6 drinks per day for men; greater than 2 drinks per day for women

(ii) One study – very heavy drinkers (average > 10 drinks per day for > 10 years) – risk of severe liver disease (cirrhosis and pre-cirrhotic lesions) approximately 50%

B.     Hepatotoxicity of drugs of abuse --- (SLIDE 5)

1.       MDMA (3,4 methyldioxymethamphetamine) – “Ecstasy”4,5,6

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 – possible explanations:

i. Hyperpyrexia

ii. Immune-mediated injury

2.       Cocaine

a.       Direct hepatic injury uncommon in humans – possible causes of hepatotoxicity 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 – 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 are using

b.       Hepatitis - “Peliosis hepatitis”

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 (few cases)10

C.     Indirect damage11

1.       Secondary to systemic effects of drugs and alcohol

a.       Hypo and hyperthermia – e.g. PCP, cocaine

b.       Shock

c.       Ischemia – e.g. cocaine

2.       Indirect damage to the liver from acquired illnesses – most common - viral hepatitis

a.       Hepatitis A

i. Transmitted via fecal-oral route

ii. Patients with substance use disorders at higher risk for acquiring this 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



A.     Importance – 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 “non-A non-B” hepatitis are HCV12

d.       Leading indication for liver transplantation in the US12

2.       Epidemiologic data – 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 and incarcerated persons – 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 – (400,000 in US have serious liver disease)

d.       10-20,000 deaths/year

B.     Hepatitis C virus16 --- (SLIDE 7)

1.       Description

a.       Small, enveloped, single-stranded RNA virus – Flaviviridae family (related to yellow fever virus)

b.       Mutates rapidly – obstacle to vaccine development – (none currently available)

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) – 20-30% of cases in US

c.       Genotype 4 – most common genotype of Africa and Middle East

d.       Genotype 5 – South Africa; Genotype 6 – 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 only confers 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 – 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 – prevalence in health care workers higher than general population (up to 3-4x prevalence)

i. Needlestick injuries – risk about 1.8% with each exposure to HCV-contaminated needles

ii. Other exposures to infected blood

d.       Intravenous drug use - sharing of needles contaminated with HCV

e.       Intranasal drug use – theoretical exposure to blood from contaminated straws17

f.        Tattoos – much controversy

i. Conflicting studies - different patient cohorts and different methodology

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 or trauma causing bleeding20

i. Sex – 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 – uncommon21

i. Rate = 4-7% when mother has active HCV infection and detectable HCV viral RNA

ii. Risk increases with maternal HIV infection to up to 20% - may correlate 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 – virus does 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 in 97% of infected persons within 6 months

d.       Some clear the virus after initial infection – “early viral clearance” – associated 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 – unclear association with HCV infection

(ii) Nonspecific – except in patients with severe liver disease

ii. Physical examination – often normal

iii. Laboratory studies

(a) May be normal

(b) ALT (SGPT) > AST (SGOT) –these enzymes range from normal to 10x normal in chronic HCV

(c) Other tests – 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 – no active liver disease

(b) Small percentage – 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) - up to 15% over 20-30 years

v. Hepatocellular carcinoma – 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 – develop in 1-2%; may occur in absence of significant liver disease

i. Cryoglobulinemia – most common –

(a) Cryoglobulins

(i) Immunoglobulins - precipitate at < 37 degrees C

(ii) Re-dissolve with warming

(iii) Associated with HCV and other conditions - exact pathogenesis unclear

(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 – enhanced pigmentation, increased skin fragility, skin trauma and fragility, vesicular and ulcerative lesions, sclerodermatous changes



A.     What is the connection?

1.       High prevalence of all forms of hepatitis in patients with alcohol and substance use disorders

2.       Prevalence of hepatitis C (HCV) in patients with alcohol and substance use disorders

a.       Alcohol use disorders – approximately 10%24

b.       Substance use disorders – 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 – 60-80% with HCV had alcohol and/or substance 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 and hepatitis C --- (SLIDE 12)

a.       Transmission/risk factors

i. Acquisition

ii. Implications for prevention of hepatitis C

b.       Natural history of illness – impact of comorbid substance use on course and outcome of hepatitis C

c.       HCV treatment – effects of comorbid substance use on antiviral treatment

d.       Implications for patient care – patients with substance use disorders and HCV

i. Prevention

ii. Improving outcomes – 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 – high risk sexual activity, tattoos

ii. ?Associated with concurrent heavy alcohol use

iii. ?Associated with decreased immune response – alcohol, marijuana may have adverse effects on immune response

2.       Risk with different drugs – route of use rather than drug of use appears to 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 – up to 80% infected within one year; 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 general population; increased prevalence even in absence of other risk factors24,29

a.       Data from studies of patients presenting for general medical care and for detoxification

b.       30% of alcohol-dependent persons with liver disease are HCV+ 24

2.       Proposed mechanisms

a.       Enabling initial infection - decreased immune response - allows survival and 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 infection –likely 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 and dissemination throughout body after initial infection

2.       Alcohol effects on inflammation, fibrosis, development of cirrhosis13,29 – 42

a.       Numerous studies – most in patients with heavy alcohol consumption (at least 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 cirrhosis in HCV+ patients with heavy alcohol use vs. no alcohol use - patients with heavy alcohol use and HCV – 10 times more likely to develop cirrhosis --- (SLIDE 17)

g.       Increased risk of end stage liver disease and death

h.       Most studies show increased inflammation, increased rates of fibrosis and 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 enhance hepatotoxicity

F.      Cigarette smoking and course of HCV infection 43,44

1.       Animal studies – 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



A.     Brief overview - treatment of HCV45,46,47 --- (SLIDE 20)

1.       Interferon

a.       Protein synthesized by organism in response to viral infection

b.       Natural antiviral activity

c.       Standard interferon – given 3x per week via IM injection

d.       “Pegylated” interferon – modified chemically by addition of polyethylene glycol

i. Prolongs half-life

ii. Given once weekly via IM injection

2.       Ribavirin

a.       Oral antiviral agent – 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 – pegylated interferon and ribavirin --- (SLIDE 21)

a.       Genotype 1 – 48 weeks of treatment

b.       Genotypes 2 and 3 – 24 weeks of treatment

c.       Compliance essential – patients must take 80% or more of doses to respond

4.       Treatment outcome

a.       Successful treatment defined as: no detectable HCV viral RNA in serum 24 weeks after course of treatment is complete (termed SVR or sustained viral response)

b.       > 90% of those with sustained viral response have no detectable serum viral 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 – 40-50% sustained viral response

(b) Genotypes 2,3 – 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 – diagnosis of chronic HCV, increased liver function tests, evidence of liver disease on biopsy

ii. Demographics of patients (in general, differs somewhat from trial to trial)

(a) Average age – early 40s

(b) Male:Female = 2:1

(c) Most patients Caucasian

(d) >60% genotype 1

b.       Initially interferon alone for 24 weeks – response rate = 6%

c.       Interferon alone for 48 weeks – response rate = 16%

d.       Interferon + ribavirin for 24 weeks – response rate = 33%

e.       Interferon + ribavirin for 48 weeks – response rate = 45%

f.        Pegylated interferon (long acting preparation) + ribavirin for 48 weeks –response 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 – 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 – up to 40%

i. Depression – most common

ii. Anxiety, agitation, irritability

iii. Insomnia

iv. Cognitive difficulties

v. Psychosis – various diagnoses included - <1% of patients

(a) Mania

(b) Delirium

(c) Presence of psychotic symptoms without diagnosis

B.     History – Treatment of HCV in patients with alcohol and other substance use disorders 12 --- (SLIDE 24)

1.       1997 NIH Conference on Management of Hepatitis C

a.       Excluded all active users of alcohol and drugs from antiviral treatment of HCV

b.       6 months abstinence required from alcohol/drugs prior to evaluation for HCV treatment

c.       Majority of patients with HCV excluded from treatment (remember comorbidity data)

2.       2002 NIH Conference on Management of Hepatitis C

a.       Eliminated exclusionary criteria for antiviral treatment of HCV for users of alcohol and drugs

b.       Recommended abstinence from alcohol and drugs for all patients prior to HCV treatment

c.       Recognized safe and effective treatment of HCV in patients with alcohol and substance use disorders possible

i. Ongoing heavy alcohol use – 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 – not an absolute contraindication to HCV treatment – suggested considering patients on case-by-case basis for antiviral treatment

d.       Recognized need to treat these patients

i. High prevalence of HCV

ii. Prevent spread of HCV

e.       Co-management strategies recommended – concurrent treatment by chemical dependency programs and hepatology clinics

C.     Alcohol - treatment of HCV in heavy users of alcohol 12,34 -- (SLIDE 25)

1.       Abstinence – strongly recommended during antiviral treatment for all patients

a.       Improvement in liver function tests – especially AST and ALT

b.       Improvement in liver disease – 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 interferon-induced neuropsychiatric disorders

(c) Alcohol interferes with antiviral actions of interferon48,49,50,51

(i) Patients drinking alcohol during antiviral treatment - response to interferon inversely correlated with level of alcohol intake during antiviral treatment

(ii) Patients with history of alcohol use who are abstinent during antiviral 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 – several reported cases in the literature52

b.       Patients with heavy alcohol use and alcohol use disorders

i. Abstinence required prior to initiation of antiviral treatment – chemical 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 – increased toxicity, decreased efficacy, adverse drug interactions – no evidence in studies to date

b.       Strongest predictor of treatment response – compliance with antiviral regimen, not relapse or ongoing drug use

c.       Interferon appears safe and effective in the few studies performed to date

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 – can patients with drug problems be compliant?

i. Programs specifically designed to treat medical conditions in drug users – rates of compliance comparable to general population

b.       Exacerbation of psychiatric illness

i. Drug users – high incidence of comorbid psychiatric illness

ii. Drugs of abuse – cause/exacerbate most psychiatric symptoms

iii. No data to support this concern – anecdotal reports of some problems

c.       Precipitation of relapse to drug use

i. Interferon side effects - similar to withdrawal states – induce craving for drugs to alleviate symptoms

ii. Self-injection with interferon may precipitate relapse into IV drug use

iii. Increased psychiatric symptoms

iv. No data – some anecdotal reports of problems

d.       Re-infection with HCV with relapse to use of intravenous drugs

(a) 2 studies – 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 dependency professionals) strongly encouraged – may enhance outcomes

E.      Summary of treatment recommendations – patients with alcohol and substance 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 strategies may enhance outcomes

2.       Other substance use disorders

b.       Individualized approach – consider treatment on case-by-case basis

c.       Recognize, manage risks – noncompliance, relapse, psychiatric complications

d.       Education, chemical dependency treatment, co-management strategies recommended



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 – so they don’t spread HCV

2.       Decreasing morbidity and mortality from HCV

a.       Education, chemical dependency treatment – decrease progression to cirrhosis, hepatocellular carcinoma

b.       Antiviral treatment

3.       Decreasing prevalence of HCV in population with substance use disorders may 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 – what we have discussed --- (SLIDE 32)

1.       Importance of HCV – 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 use disorders

b.       High prevalence of substance use disorders in patients with HCV

3.       Drugs, alcohol and HCV – what we know

a.       Transmission/risk factors

i. Alcohol – risk factor for HCV because of effects on immune response

ii. Drug use – users of injected drugs high risk for HCV – exposure to infected blood

b.       Natural History

i. Alcohol – known to accelerate serious liver damage from HCV

ii. Drugs – unknown effects on liver damage from HCV; additive hepatotoxicity 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



1.                    Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL (eds): Harrison’s Principles of Internal Medicine, 15th Edition. New York, McGraw-Hill, 2001

2.                    Friedman SL: Pathogenesis and frequency of development of alcoholic liver disease. UpToDate Online 11.3 2003; (accessed 12/20/2003)

3.                    Lelbach WK: Cirrhosis in the alcoholic and its relation to the volume of alcohol abuse. Ann NY Acad Sci 1975; 252:85-105

4.                    Jones AL, Simpson KJ: Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications. Aliment Pharmacol Ther 1999; 13:129-133

5.                    Henry JA, Jeffreys KJ: Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ecstasy”). 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 Hepatology 1998; 29:394-397

7.                    Selim K, Kaplowitz N: Hepatoxicity of psychotropic drugs. Hepatology 1999; 29:347-351

8.                    Lukas SE: The pharmacology of steroids, in Principles of Addiction Medicine. 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/anabolic steroid-induced toxic hepatitis. Journal of Clinical Gastroenterology 2002; 35:350-352

10.                Armen R, Kanel G, Reynolds T: Phencyclidine induced malignant hyperthermia causing submassive liver necrosis. American Journal of Medicine 1984; 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 Addiction Medicine, 2003

12.                Seeff LB, Hoofnagle JH: National Institutes of Health consensus development conference: management of hepatitis C: 2002. Hepatology 2002; 36:S1-S20

13.                Kim WR: The burden of hepatitis C in the United States. Hepatology 2002; 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 the United States, 1988-1994. New England Journal of Medicine 1999; 341:556-562

15.                Marsano LS: Hepatitis. Primary Care Clinics in office practice 2003; 30:81-107

16.                Hoofnagle JH: Course and outcome of hepatitis C. Hepatology 2002; 36:S21-S29

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 virus infection. 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 important source of hepatitis C infection: clinical epidemiology of 626 consecutive patients 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 virus infection. Hepatology 2002; 36:S106-S113

22.                Seeff LB: Natural history of chronic hepatitis C. Hepatology 2002; 36:S35-S46

23.                Thomas DL, Astemborski J, Rai RM, et al.: The natural history of hepatitis 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 disorders among veterans with hepatitis C infection. Gastroenterology 2002; 123:476-482

26.                Lehman LL, Cheung RC: Depression, anxiety, post-traumatic stress and alcohol-related problems among veterans with chronic hepatitis C. American Journal of Gastroenterology 2002; 97:2640-2646

27.                Straits-Troster KA, Sloan KL, Dominitz JA: Psychiatric and substance use disorder comorbidity with hepatitis C. Psychiatric Annals 2003; 33:362-366

28.                Davis GL, Rodrigue JR: Treatment of chronic hepatitis C in active drug users. New England Journal of Medicine 2001; 345:215-217

29.                Schiff ER: The alcoholic patient with hepatitis C virus infection. Am J Medicine 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 consumption on 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 C virus RNA levels among alcoholic patients with chronic hepatitis C. Hepatology 1994; 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 the histological and clinical progression of hepatitis C infection. Hepatology 1998; 28:805-809

36.                Tanaka T, Yabusako T, Yamashita T, et al.: Contribution of hepatitis C virus 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 the progression of liver disease caused by hepatitis C virus infection. Hepatology 1998; 27:1731-1735

38.                Loguercio C, Di Pierro M, Marino MPD, et al.: Drinking habits of subjects with hepatitis C virus-related chronic liver disease. Alcohol and Alcoholism 2000; 35:296-301

39.                Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression 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 risk factors of hepatitis C related liver disease in the general population: report from the Dionysos study. Gut 1999; 44:874-880

42.                Noda K, Yoshihara H, Suzuki K, et al.: Progression of type C chronic hepatitis to liver cirrhosis and hepatocellular carcinoma. Alcohol Clin Exp Res 1996; 20:95A-100A

43.                Hezode C, Lonjon I, Roudot-Thoraval F, et al.: Impact of smoking on histological liver lesions in chronic hepatitis C. Gut 2003; 52:126-129

44.                Pessione F, Ramond M, Njapoum C, et al.: Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology 2001; 34:121-125

45.                Lindsay KL: Introduction to therapy of hepatitis C. Hepatology 2002; 36:S114-S120

46.                Bisceglie AM, Hoofnagle JH: Optimal therapy of hepatitis C. Hepatology 2002; 36:S121-S127

47.                Fried MW, Shiffman ML, Reddy K et al.: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C infection. New England Journal of Medicine 2002; 347:975-982

48.                Ono K, Sata M, Murashima S, et al.: Biological responses to administered interferon in alcoholics. Alcohol Clin Exp Res 1996; 20:1560-1563

49.                Okazaki T, Yoshihara H, Suzuki K, et al.: Efficacy of interferon therapy in patients with chronic hepatitis C. Comparison between non-drinkers and drinkers. Scand J Gastroenterol 1994; 29:1039-1043

50.                Ohnishi K, Matsuo S, Matsutani K, et al.: Interferon therapy for chronic hepatitis C in habitual drinkers: comparison with chronic hepatitis C in infrequent drinkers. Am J Gastroenterol 1996; 91:1374-1379

51.                Tabone M, Sidoli L, Laudi C, et al.: Alcohol abstinence does not offset the strong negative effect of lifetime alcohol consumption on the outcome of interferon therapy. J Viral Hepat 2002; 9:288-294

52.                Zylberberg H, Fontaine H, Thepot V, et al.: Triggering of acute alcoholic hepatitis by α-interferon therapy. J Hepatol 1999; 30:722-725

53.                Edlin B: Prevention and treatment of hepatitis C in injection drug users. 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 of hepatitis C infection in injection drug users. Hepatology 2001; 34:188-193