Hepatitis CHepatitis C

Joyce Sutton, M.D.Joyce Sutton, M.D.

HIV and HCV in CDCHIV and HCV in CDC

1994 and 1999 anonymous tests of all inmates entering prison during a two month period. 5000+ each time.

1994 and 1999 anonymous tests of all inmates entering prison during a two month period. 5000+ each time.

ResultsResults

1994 HIV 2.5% HCV 41% 1999 HIV 1.4% HCV 34.6%

NYC inmates 16% positive for HIV

1994 HIV 2.5% HCV 41% 1999 HIV 1.4% HCV 34.6%

NYC inmates 16% positive for HIV

Incidence of HCV in other populations

Incidence of HCV in other populations

US overall 1.8% NYC Oral Surgeons-9% 1990 Egypt overall 18% Sacramento clinic for IVDU 95% 2000 California state hospital patients 25% Psychiatric outpatients in US 5-20% Sacramento Co. Jail 1999- 28%

US overall 1.8% NYC Oral Surgeons-9% 1990 Egypt overall 18% Sacramento clinic for IVDU 95% 2000 California state hospital patients 25% Psychiatric outpatients in US 5-20% Sacramento Co. Jail 1999- 28%

History of HCVHistory of HCV

1970’s non-A, non-B hepatitis 1989 HCV cloned, blood tests available 1990 Interferon approved for Tx 1990 ribaviron added to Tx 2001 Pegelated interferon approved

1970’s non-A, non-B hepatitis 1989 HCV cloned, blood tests available 1990 Interferon approved for Tx 1990 ribaviron added to Tx 2001 Pegelated interferon approved

Hepatitis reviewHepatitis review

Hep A

. Food borne (oysters, etc) Oral-fecal spread (un-washed hands,

dishes) Acute symptoms (fever, jaundice, malaise) Most persons recover completely

Hep A

. Food borne (oysters, etc) Oral-fecal spread (un-washed hands,

dishes) Acute symptoms (fever, jaundice, malaise) Most persons recover completely

Hep BHep B

Blood to blood transmission (needles, transfusions)

Most persons recover, 5-20% develop chronic infection, 5% cirrhosis and death

10x more contagious than HCV 100x more than HIV

Blood to blood transmission (needles, transfusions)

Most persons recover, 5-20% develop chronic infection, 5% cirrhosis and death

10x more contagious than HCV 100x more than HIV

1990 vaccine approved for Hep A and Hep B

Before then, infection of health care personnel was common

State hospital and CDC dentists- 75% became infected 25 years ago

Royal Air Force, England 1940’s and 1960’s outbreaks of jaundice and hepatitis in troupes from re-use of injection syringes

1990 vaccine approved for Hep A and Hep B

Before then, infection of health care personnel was common

State hospital and CDC dentists- 75% became infected 25 years ago

Royal Air Force, England 1940’s and 1960’s outbreaks of jaundice and hepatitis in troupes from re-use of injection syringes

Hep C (HCV)Hep C (HCV)

Rapidly mutating RNA virus, develops many sub-populations of HCV “quasi-species”

Difficult for immune system to eradicate, and difficult to develop vaccine or effective treatment

Blood to Blood transmission

Rapidly mutating RNA virus, develops many sub-populations of HCV “quasi-species”

Difficult for immune system to eradicate, and difficult to develop vaccine or effective treatment

Blood to Blood transmission

Methods of transmission in USMethods of transmission in US

IV drug use 65% of patients Transfusions 15% (before 1989) Dialysis 7% Fetus 2% Needle stick 1% (accidents). Unknown 10% . Sexual Transmission- low risk

IV drug use 65% of patients Transfusions 15% (before 1989) Dialysis 7% Fetus 2% Needle stick 1% (accidents). Unknown 10% . Sexual Transmission- low risk

Transmission in prisonTransmission in prison

Shared needles Tattoos ink is saved and re-used Other shared personal items (toothbrushes,

razors, nail clippers)

Shared needles Tattoos ink is saved and re-used Other shared personal items (toothbrushes,

razors, nail clippers)

Transmission to FetusTransmission to Fetus

3-7% of babies of HCV+ mothers No medication to prevent this Interferon and ribaviron both cause severe birth

defects Most babies do well without treatment 50% eradicate virus by 6 months 75% eradicate virus by one year.

3-7% of babies of HCV+ mothers No medication to prevent this Interferon and ribaviron both cause severe birth

defects Most babies do well without treatment 50% eradicate virus by 6 months 75% eradicate virus by one year.

Natural History of HCV infectionNatural History of HCV infection

No symptoms for many years or decades, most cases detected by blood test.

Mild symptoms may occur: fatigue, itching, RUQ discomfort

25% clear virus, 75% chronic infection 25% progress to Fibrosis-Cirrhosis 5% develop liver cancer

No symptoms for many years or decades, most cases detected by blood test.

Mild symptoms may occur: fatigue, itching, RUQ discomfort

25% clear virus, 75% chronic infection 25% progress to Fibrosis-Cirrhosis 5% develop liver cancer

25%+ will develop type II Diabetes ANY alcohol use accelerates

progression to Fibrosis and Cirrhosis HIV co-infection greatly accelerates

progression of HCV (decreases immune response) 30%+ of HIV patients also have HVC. HCV is becoming a major cause of death in treated HIV patients.

25%+ will develop type II Diabetes ANY alcohol use accelerates

progression to Fibrosis and Cirrhosis HIV co-infection greatly accelerates

progression of HCV (decreases immune response) 30%+ of HIV patients also have HVC. HCV is becoming a major cause of death in treated HIV patients.

6 genotypes and over 50 subtypes

6 genotypes and over 50 subtypes

1 Most common US and Canada 60-75% 2+3 25% Us and Canada 4,5 +6 less then 5% US and Canada 4 most common type in Egypt

1 Most common US and Canada 60-75% 2+3 25% Us and Canada 4,5 +6 less then 5% US and Canada 4 most common type in Egypt

TreatmentTreatment

Least effective (45% SVR) for the most common HCV genotype (type I- 75% of cases)

Most effective (80% SVR) for the least common genotypes (2&3-25%)

Many side effects, very unpleasant Can delay Tx if disease not progressing rapidly

and hope for better Tx later.

Least effective (45% SVR) for the most common HCV genotype (type I- 75% of cases)

Most effective (80% SVR) for the least common genotypes (2&3-25%)

Many side effects, very unpleasant Can delay Tx if disease not progressing rapidly

and hope for better Tx later.

Early Treatment RecommendedEarly Treatment Recommended

Genotypes 2+3- better results 80% SVR Shorter treatment duration 24 weeks Possible lower dose ribavirin Consider treatment after needle stick injury

if infection results

Genotypes 2+3- better results 80% SVR Shorter treatment duration 24 weeks Possible lower dose ribavirin Consider treatment after needle stick injury

if infection results

Absolute Contraindications to Treatment

Absolute Contraindications to Treatment

Age less than 3 Poor compliance Decompensated liver Disease (except pre-

transplant) Ongoing and Untreated Substance Abuse Pregnancy or nonadherence to

contraceptive use during Tx and 6mos after

Age less than 3 Poor compliance Decompensated liver Disease (except pre-

transplant) Ongoing and Untreated Substance Abuse Pregnancy or nonadherence to

contraceptive use during Tx and 6mos after

Co-existing Medical Disorders and contraindications

Co-existing Medical Disorders and contraindications

Uncontrolled seizure disorder Uncontrolled severe Psychiatric Disorder Autoimmune diseases, including SLE and

Rheumatoid Arthritis Solid Organ Transplantation (except liver)

Uncontrolled seizure disorder Uncontrolled severe Psychiatric Disorder Autoimmune diseases, including SLE and

Rheumatoid Arthritis Solid Organ Transplantation (except liver)

Severe Anemia, Neutropenia, Thrombocytopenia

Uncontrolled Heart disease (angina, congestive failure, significant arrhythmias)

Cerebrovascular disease Advanced Renal failure

Severe Anemia, Neutropenia, Thrombocytopenia

Uncontrolled Heart disease (angina, congestive failure, significant arrhythmias)

Cerebrovascular disease Advanced Renal failure

Serologic TestingSerologic Testing

HCV antibodies (anti-HCV) EIA 95-99% sensitivity- inexpensive 6-8 weeks after exposure HCV-RNA assay (qualitative-PCR) Detects viral RNA - expensive 1-3 weeks after exposure

HCV antibodies (anti-HCV) EIA 95-99% sensitivity- inexpensive 6-8 weeks after exposure HCV-RNA assay (qualitative-PCR) Detects viral RNA - expensive 1-3 weeks after exposure

Who should be tested for HCV-RNA

Who should be tested for HCV-RNA

Inconclusive anti HCV PCR Immunocompromised (HIV, transplant

patient, hemodialysis) Suspected acute infection (needle stick) Positive HCV, but persistently low normal

ALT (may have cleared virus)

Inconclusive anti HCV PCR Immunocompromised (HIV, transplant

patient, hemodialysis) Suspected acute infection (needle stick) Positive HCV, but persistently low normal

ALT (may have cleared virus)

MonitoringMonitoring

Follow LFT, especially ALT(indicates inflammation)

Follow FBS and 2h pp glucose (glucose intolerance increases as disease progresses)

Test for genotype and viral titer Liver biopsy before Tx (Only way to know

how far disease has progressed)

Follow LFT, especially ALT(indicates inflammation)

Follow FBS and 2h pp glucose (glucose intolerance increases as disease progresses)

Test for genotype and viral titer Liver biopsy before Tx (Only way to know

how far disease has progressed)

Course of TreatmentCourse of Treatment

Goal- complete irradication of virus sustained for 6 months after Tx stopped

Studies at 3 and 13 years after SVR indicate durable results

Length of Tx and dose depends on genotype

Goal- complete irradication of virus sustained for 6 months after Tx stopped

Studies at 3 and 13 years after SVR indicate durable results

Length of Tx and dose depends on genotype

Type I (75%) Continue Tx for 48 weeks+ Peg Interferon (weekly sub-Q ) and

Ribaviron 1000-1200mg daily Type 2 & 3 (25%) Continue Tx 24 weeks Peg Interferon (weekly Sub Q) and

Ribaviron 800mg daily

Type I (75%) Continue Tx for 48 weeks+ Peg Interferon (weekly sub-Q ) and

Ribaviron 1000-1200mg daily Type 2 & 3 (25%) Continue Tx 24 weeks Peg Interferon (weekly Sub Q) and

Ribaviron 800mg daily

12 week treatment test12 week treatment test

All genotypes, repeat viral titer at 12 weeks If less than 2 LOG decrease in viral titer,

STOP TREATMENT Less than 3% chance of response, does not

justify risks of treatment

All genotypes, repeat viral titer at 12 weeks If less than 2 LOG decrease in viral titer,

STOP TREATMENT Less than 3% chance of response, does not

justify risks of treatment

24 week treatment test24 week treatment test

All genotypes, repeat viral titer at 24 weeks. Titer should be ZERO. If not, STOP

TREATMENT Less than 3% chance of response and

continued treatment does not justify the risks

All genotypes, repeat viral titer at 24 weeks. Titer should be ZERO. If not, STOP

TREATMENT Less than 3% chance of response and

continued treatment does not justify the risks

Adverse effects of TreatmentAdverse effects of Treatment

Bone marrow suppression- Neutropenia, anemia, decreased platelets

Contraindicated with clozaril Problematic with HIV patients who are

immunosuppressed. However, many HIV patients have been successfully treated. Response rates are similar to other patients.

Bone marrow suppression- Neutropenia, anemia, decreased platelets

Contraindicated with clozaril Problematic with HIV patients who are

immunosuppressed. However, many HIV patients have been successfully treated. Response rates are similar to other patients.

Flu-like symptoms-can be severe: malaise, headache, muscle aches, nausea, fever, anorexia,

Psychiatric symptoms: depression and irritability, can be severe. 60% of non psychiatric patients become depressed.

SSRI medications helpful (prozac, etc.) Relative contraindication in psychiatric

patients. However, many state hospital patients have been successfully Tx. Requires close observation and increased medications. (increased suicide risk)

Flu-like symptoms-can be severe: malaise, headache, muscle aches, nausea, fever, anorexia,

Psychiatric symptoms: depression and irritability, can be severe. 60% of non psychiatric patients become depressed.

SSRI medications helpful (prozac, etc.) Relative contraindication in psychiatric

patients. However, many state hospital patients have been successfully Tx. Requires close observation and increased medications. (increased suicide risk)

Needle SharingNeedle Sharing

Sacramento drug Tx clinics 2000 Meth users- 30% inject 43% often did not

sterilize Meth users- shared with 11 strangers /yr casual sex with 8 partners Heroin users- shared with 3.4 strangers /yr casual sex with 2.6 partners

Sacramento drug Tx clinics 2000 Meth users- 30% inject 43% often did not

sterilize Meth users- shared with 11 strangers /yr casual sex with 8 partners Heroin users- shared with 3.4 strangers /yr casual sex with 2.6 partners

Needle Exchange ProgramsNeedle Exchange Programs

2002 Mar 13 Int. J of STD and AIDS New Haven, Co. Needles were “tagged” to identify “owner” 31.5% were returned by different “owner”

2002 Mar 13 Int. J of STD and AIDS New Haven, Co. Needles were “tagged” to identify “owner” 31.5% were returned by different “owner”

Unsafe Injections and Blood Bourne Disease

World Wide Problem

Unsafe Injections and Blood Bourne Disease

World Wide Problem

Developing world (Africa, Asia, Central and South America, Mexico, Romania)

50% of injections are un-sterile, and other medical practices are un-safe

Developed countries-Shared Needles of drug usersUnsafe cosmetic practices (nail salons, piercing,

tattoos).

Developing world (Africa, Asia, Central and South America, Mexico, Romania)

50% of injections are un-sterile, and other medical practices are un-safe

Developed countries-Shared Needles of drug usersUnsafe cosmetic practices (nail salons, piercing,

tattoos).

Cultural DifferencesCultural Differences

Nothing of value is thrown away or wasted Injections are “magic” Are the most effective way to deliver

powerful and expensive medicine Overuse of injections 90% not needed

(vitamins,antibiotics,analgesics) 10% vaccinations

Lack of understanding of sanitation and blood bourne disease

Nothing of value is thrown away or wasted Injections are “magic” Are the most effective way to deliver

powerful and expensive medicine Overuse of injections 90% not needed

(vitamins,antibiotics,analgesics) 10% vaccinations

Lack of understanding of sanitation and blood bourne disease

Unsafe injections may spread HIV more than sex

Unsafe injections may spread HIV more than sex

Controversial -Interesting data “Deep” injuries may be 10X more likely to infect

than superficial needle pricks. Account for over 50% of infections in health care workers, yet are only 10% of accidents.

HIV+ children- 20% have HIV- mothers Pre-natal care and delivery (Kenya,Zimbabwe,S.

Africa) 5-19% of HIV- women become HIV+ Puerperal fever rates in Vienna 1841-46 6-

16% (Semmelweis)

Controversial -Interesting data “Deep” injuries may be 10X more likely to infect

than superficial needle pricks. Account for over 50% of infections in health care workers, yet are only 10% of accidents.

HIV+ children- 20% have HIV- mothers Pre-natal care and delivery (Kenya,Zimbabwe,S.

Africa) 5-19% of HIV- women become HIV+ Puerperal fever rates in Vienna 1841-46 6-

16% (Semmelweis)

Romania 1990- 14% of orphans 0-3 yrs old tested HIV+ (1000+ )

Origin- imported gamaglobulin given to a few kids and spread to rest by un-safe injections.

One orphanage records: 1989 Given- 4457 injections Sterilized- 810 syringes (82% Not sterilized)

Pediatric clinics in Africa re-use needles 3-20% of children are HIV+

Infants have viral loads 10-100x adults No investigation of infections is done

Romania 1990- 14% of orphans 0-3 yrs old tested HIV+ (1000+ )

Origin- imported gamaglobulin given to a few kids and spread to rest by un-safe injections.

One orphanage records: 1989 Given- 4457 injections Sterilized- 810 syringes (82% Not sterilized)

Pediatric clinics in Africa re-use needles 3-20% of children are HIV+

Infants have viral loads 10-100x adults No investigation of infections is done

Thousands of paid blood donors in China are infected with HIV.

One Chinese village, 50-70% of older people have HCV from clinic injections before 1985

Egypt- 18% of population is HCV+ -injections for shistosomiasis 1920-1980

1950,s-1980’s massive increase in Medical injections in Africa- vaccinations and treatment of yaws. Time of silent spread of HIV

The River- Source of HIV may have been early polio vaccine trials in Africa using monkey kidney cultures

Thousands of paid blood donors in China are infected with HIV.

One Chinese village, 50-70% of older people have HCV from clinic injections before 1985

Egypt- 18% of population is HCV+ -injections for shistosomiasis 1920-1980

1950,s-1980’s massive increase in Medical injections in Africa- vaccinations and treatment of yaws. Time of silent spread of HIV

The River- Source of HIV may have been early polio vaccine trials in Africa using monkey kidney cultures

Hepatitis C and diabetesHepatitis C and diabetes

Incidence of Hepatitis CIncidence of Hepatitis C

CDC 35-38% of inmates at reception center 1994 + 1999

DMH 25-30% state hospital patients US population 1.8% US Psychiatric outpatients 5-20% Sacramento drug tx program 95% Egypt general population 18%

CDC 35-38% of inmates at reception center 1994 + 1999

DMH 25-30% state hospital patients US population 1.8% US Psychiatric outpatients 5-20% Sacramento drug tx program 95% Egypt general population 18%

Diabetes and Hepatitis Diabetes and Hepatitis

Hep C increases insulin resistance Hep C is an independent risk factor Hep C is additive to other risk factors Diabetes risk increases as the liver disease

advances (13-33%non-cirrhotic mean 25%) (50%+ cirrhotic) No-one has studied the diabetes risk of Hep C in

Psychiatric patients or the interactions with Psychiatric medications

Hep C increases insulin resistance Hep C is an independent risk factor Hep C is additive to other risk factors Diabetes risk increases as the liver disease

advances (13-33%non-cirrhotic mean 25%) (50%+ cirrhotic) No-one has studied the diabetes risk of Hep C in

Psychiatric patients or the interactions with Psychiatric medications

Eli Lilly(Olanzapine)

Eli Lilly(Olanzapine)

Clinical trials eliminated any patients with known liver disease

They had not thought about the combined effects of Hep C and Olanzapine re diabetes

They are interested in funding clinical studies

Clinical trials eliminated any patients with known liver disease

They had not thought about the combined effects of Hep C and Olanzapine re diabetes

They are interested in funding clinical studies

Diabetes may increase the progression of HCV to cirrhosis

Test all patients for HCV and HBV Consider medications with less potential

for weight gain in HCV+ Monitor HCV+ more closely for diabetes

Diabetes may increase the progression of HCV to cirrhosis

Test all patients for HCV and HBV Consider medications with less potential

for weight gain in HCV+ Monitor HCV+ more closely for diabetes

SGA’S and weight gainSGA’S and weight gain

Drug Weight gain

Clozapine +++

Olanzapine +++

Risperidone ++

Quetiapine ++

Aripiprazole +/-

Ziprasidone +/-

amantadineamantadine

Has some antiviral activity against Hep C Helps to prevent depression during Hep C

treatment May stop weight gain from antipsychotics As effective as cogentin or artane for EPS

side effects

Has some antiviral activity against Hep C Helps to prevent depression during Hep C

treatment May stop weight gain from antipsychotics As effective as cogentin or artane for EPS

side effects

HVC Self CareHVC Self Care

Abstain from all alcohol Maintain normal body weight Exercise Avoid Herbal Products, especially Kava- these are

not effective and many are toxic to the liver Do not take Iron supplements (buy senior

vitamins) Avoid NSAIDS

Abstain from all alcohol Maintain normal body weight Exercise Avoid Herbal Products, especially Kava- these are

not effective and many are toxic to the liver Do not take Iron supplements (buy senior

vitamins) Avoid NSAIDS

HCV PreventionHCV Prevention

Do not share needles Do not use Health Care in developing countries

(includes blood tests and acupuncture) buy Medical Evacuation Insurance (SOS, AAA)

Evaluate carefully nail salons- bring your own tools. (also tattoo and piercing parlors)

Do not use nail salons in Developing countries

Do not share needles Do not use Health Care in developing countries

(includes blood tests and acupuncture) buy Medical Evacuation Insurance (SOS, AAA)

Evaluate carefully nail salons- bring your own tools. (also tattoo and piercing parlors)

Do not use nail salons in Developing countries