Hepatitis C Update: A Primary Care Perspective

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Hepatitis C Update A Primary Care Perspective

• Jay Fathi, M.D.
• February 2003

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Overviewan epidemic

• RNA virus discovered by cloning in 1988
• First serologic test 1990
• Approximately 4 million Americans infected most
  common liver disease in US, most common
  indication for transplantation
• Roughly 30,000 new cases annually only 30
  diagnosed

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Overview (cont.)

• 85 become chronically infected
• 10,000 deaths annually
• Incidence falling recently prevalence increasing
  over last decade

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Natural Course

• Acute infection asymptomatic or mild illness
• Virus detectable by PCR-RNA in 2-4 weeks after
  exposure usually
• Roughly 15 spontaneously clear virus remain
  Ab-positive but are PCR-RNA negative
• 20 (3-30 depending on study) develop cirrhosis,
  usually over many years
• Alcohol, co-morbid HIV, Hep B increase risk

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Natural Course (cont.)

• 20 cirrhotic patients (5 of total) develop
  hepatocellular carcinoma survival after Dx of
  HCC is 6 months-2 years
• Clinic course varies greatly case by case

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Transmission

• Contaminated blood most infectious (transfusions
  prior to 1992, now needle-sharing, intranasal
  cocaine)
• Sexual transmission (less than 5)
• Perinatal transmission (approx. 5) dependent on
  maternal viral load
• Shared razors, toothbrushes, open cuts, etc.

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Transmission (cont.)

• Occupational exposure (roughly 2 with
  needlesticks)
• ALWAYS USE UNIVERSAL PRECAUTIONS

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Diagnosis

• Enzyme immunoassays
• PCR (viral load), qualitative vs. quantitative
  useful to follow treatment response
• Viral load not correlated with disease
  progression
• Genotyping (when considering treatment)
• Complete Hep screen, HIV

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LFTs

• LFTs are not well correlated with hepatic
  fibrosis
• Fairly specific poor sensitivity
• Normal LFTs somewhat reassuring, but hepatic
  fibrosis can still exist
• Biopsy-gold standard for assessing disease
  progression

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Patient Education

• Avoid hepatotoxins (esp. ALCOHOL!!!)
• General healthcare maintenance (diet, smoking
  cessation, exercise, etc.)
• Weight losscan help steatosis and may possibly
  alter course of disease
• Immunizations (Hep A, B, pneumovax, Td, flu shot,
  etc.)

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Education (cont.)

• Do not donate blood, share needles or inhalation
  devices for recreational drugs, cover wounds,
  discuss possible sexual/perinatal transmission
• Support groups

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Treatment

• 18-60 years old ()
• Persistently elevated LFTs (?)
• PCR positive, biopsy positive
• Studies currently ongoing in other populations
  (children, older adults, severe cirrhotics, etc.)

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Treatment (cont.)

• No current substance abuse
• Patient interested in therapy
• No current substance abuse, generally healthy,
  no unstable psychiatric disorders

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Treatment (cont.)

• Interferon plus oral ribavirin
• Usually 12 months, 1-3 weekly injections, very
  costly (15,000 for Ribavirin alone)
• Side effects flu-like symptoms, alopecia, bone
  marow suppression, cardiac and pulmonary
  impairment, thyroid/ocular abnormalities,
  seizures, exacerbation of any pre-existing
  psychiatric abnormalities

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Treatment (cont.)

• Pegylated interferon higher clearance rates,
  once-weekly injections, less psychiatric SE
• Lasting (?) clearance of virus in 20-50 patients
• Resposne to treatment somewhat dependent on
  genotype (1 most prevalent in US, likely most
  virulent also)
• Genotype I, previous non-responders, African
  Americans less responsive to treatment

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Treatment (cont.)

• Depression (emotional disturbances) most common
  reason for discontinuation
• 20 or more drop out of treatment before 48 week
  course completed
• Protease Inhibitors promising preliminary data
• Milk thistle? Data shows no improvement

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Frequent Co-morbidities

• HIV, Hep B, alcohol abuse, other substance abuse,
  psychiatric disorders (depression, bipolar),
  homelessness, etc.

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Suggested Management Plan

• Check PCR if negative, periodically screen with
  ALT and/or PCR (Q2-5 years?) to ensure patient
  has definitively cleared virus
• If PCR positive, assess if patient is candidate
  for therapy and give thorough counselling about
  disease/treatment/etc. to see if they are
  interested

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Management plan (cont.)

• If yes to both (PCR positive, interested in
  treatment), refer for liver biopsy
• Primary care clinician must be able to
  competently counsel patients regarding the myriad
  of complicating issues
• Each patient must be managed individually

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Hepatitis B

• Double-stranded DNA virus
• Global prevalence 5
• Approximately 400 million people!
• Mostly in SE Asia, Philippines, Middle East,
  Africa, parts of S. America
• Lowest prevalence US, Canada, N. Europe
• US 1 million chronically infected (chronic
  carriers)

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Transmission

• Blood, body fluids (saliva, semen)
• Most common mode of spread in US sexual contact
  (heterosexual and homosexual)
• Most common mode of spreas worldwide VERTICAL
  TRANSMISSION

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Acute to chronic infection

• After acute infection, 5-10 of adults become
  chronically infected
• Up to 90 of neonates become chronically infected
  when vertical transmission occurs
• HBcAB evidence of prior infection
• HBsAg chronically infected
• HBcAB and HBsAg negative prior infection,
  have cleared virus

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Chronic Hep B

• HBeAgindicative of replication and infectivity
• HBeAg Replicators, more infections, poor
  prognosis
• 15-20 progress to cirrhosis in 5 years
• HBeAg negative---- Non-replicators, less
  infectious, better prognosis
• Both should be referred to specialist for likely
  liver biopsy, treatment evaluation

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Treatment

• Interferon, 3TC (lamivudine)
• Fairly low numbers re response rates
• Hepsera (Adefovir)new treatment
• 50-60 cure rate (?) in studies
• Liver fibrosis improved on biopsy
• SE 25 can experience exacerbation of hepatitis

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Prevention

• IMMUNIZATION !!!!!!!!!!!!!!!!!!!!!!!!!
• ALL infants
• High risk adults
• All adults?