Hepatitis C Infection

Introduction

The virus's recent spread is thought to be due to receipt of blood products before the introduction of testing (Feb 1990) and to an increase in injecting drug use (IDU) in Western countries.

Hepatitis C is probably the most common life threatening infection in Australia. Over the last 20 years, an estimated 130,000 people have been infected, with an estimated 6000 new infections annually from IDU alone. Of those infected, 80-85% develop chronic liver disease. Of these, 10-20% develop cirrhosis within 20 years, and of those with cirrhosis, 5% will develop hepato-cellular carcinoma.

Universal testing by blood banks has minimised the risk of transmission via blood products. However, there is little evidence that the campaign that successfully reduced the spread of HIV (via IDU) through education, needle exchanges and methadone clinics, has had much impact on the spread of hepatitis C.

The large numbers of people infected, together with the chronicity of the disease, makes HCV a major health challenge. GPs, with their skills in long term management of chronic illness, are at the forefront of this challenge and also have an opportunity to educate IDUs about the dangers of hepatitis C.

Hepatitis C - the Virus

Generally there are low titres of the virus in the serum of infected patients. It is very difficult to grow in cell culture, and no one has ever seen the virus with electron microscopy. Viral antigens have not been classified nor are they measurable (compare this with hep B surface antigen). A positive HCV antibody test indicates infection with the virus at some stage (past and/or current). The HCV-RNA test via the PCR technique is consistently improving and a positive test indicates the presence of active infection. At the current time there is no rebate for this test and most laboratories charge about $60.

Epidemiology of Hepatitis C

Direct parenteral exposure is the major risk factor in transmission of hepatitis C

• Transfusion of blood products from infected donors; people transfused with blood prior to universal testing of all blood products in February 1990 are at risk.
• Regular transfusion of blood products; 85-90% of haemophiliacs in Australia
• are HCV antibody +ve. Blood products are now treated by a process that destroys HCV.
• IDUs sharing contaminated drug injecting equipment.

• IDUs have the highest risk rate, studies showing 75% are infected after five years rising to nearly 100% at 10 years.
• Sex industry workers have a higher rate than the general population 5-8%, but this may be more a reflection of IDU use than sexual transmission.
• Body piercing and tattooing using contaminated equipment.

Vertical transmission from mother to fetus occurs, but breast feeding is safe unless there is bleeding from the nipple. Maternal hepatitis C antibodies are transmitted passively to the fetus but disappear from circulation by 18 months. 5-10% of children acquire the virus. This is most likely to happen when there is a high viral titre, such as when hepatitis C is acquired during pregnancy, or if the mother is HIV positive.

Endoscopy before 1990 may be a risk factor.

Natural History

• About 1/4 patients may develop significant liver diseases including:
  • 20% cirrhosis after 20 years
  • 10% hepatocellular carcinoma after 30 years

The challenge of therapy is to treat patients to prevent cirrhosis and hepato cellular carcinoma (HCC) without unduly disturbing those who will have mild chronic hepatitis only.

If 100 people catch the hapatitis C virus at the same time:

• 15 - 20 people get rid of the virus within two to six months ( but will continue to carry antibodies for some time).
• 80 - 85 people have chronic (long - term) hepatitis C infection.
  • Around 20 people will never develop any liver damage or physical symptoms.
  • Between 60 to 65 people will develop some level of long term symptoms or signs of liver damage ( after an average 13 years )
    • Between 20 to 25 of these people will develop cirrhosis of the liver (over an average 20 year period)
      • Bewteen 5 to 10 of those people will experience liver failure of liver cancer (after an average 25 to 30 years, all up)

HCV Prevelance

NSW North Coast hepatitis C study

This study, conducted by the North Coast Public Health Unit, examined how hepatitis C was being transmitted on the North Coast. All people who were notified to the North Coast Public Health Unit during a 21 month study period (1993-94) were invited to complete a survey. 465 questionnaires were completed (46% of notified cases).

Direct exposure to blood could be demonstrated for almost all subjects. Risks associated with household, sexual and other contact where blood exposure was avoided appeared to be minimal.

When 57 of these positive partners were followed up only 5% (3) had no independent blood exposure. Approximately half of the HCV negative sexual partners reported having unsafe sex with their HCV positive partner, further illustrating the lack of sexual transmission.

Management of hepatitis C antibody positive patients

Checklist

PreTest Counselling

Pretest check list

• Natural history of HCV
• Transmission
• Nature and interpretation of tests
• Assessment of level of risk
• Significance of positive result
• Management and treatment of HCV
• Assessment of psychological status
• Confidentiality and notification
• Informed consent
• Information material

• Assessment of the patient's risk factors and the likelihood of a positive result.
• The significance of a positive result. A positive result does not necessarily indicate progressive liver disease.
• Transmission sexually and from mother to infant is low, but transmission to household members is possible via toothbrushes and razors.
• An outline of the management of hep C including monitoring, antiviral therapy and lifestyle changes.
• A brief psychological assessment to gain some insight into the patient's possible reaction to a positive result.
• Confirmation that confidentiality will be respected but that positive results are notifiable to the NSW Health Department.
• Allow the patient to give informed consent before testing.
• Provision of written information (see back of book for details).

Who Should Be Tested

Testing should be offered to the following:

• People who have EVER injected drugs
• People who were transfused with blood or blood products (especially prior to February 1990)
• People with abnormal liver function tests or evidence of liver disease with no apparent cause
• People with occupational exposure to HCV
• People with extra hepatic manifestations eg. Cryoglobulinaemia glomerulonephritis
• Renal dialysis patients
• People with a history of imprisonment

• People who have had tattoos, body piercing or acupuncture in a situation where infection control guidelines may not have been followed
• People from countries where there is a high prevalence (the Mediterranean, Middle East, Asia, Africa, South America)
• Children, sexual and household contacts of persons with HCV
• Health care workers
• Those requesting the test who may have a hidden agenda
• Travellers who have received medical care, injections, or transfusions in countries where HCV has a high prevalence or where blood is not tested prior to transfusion.

The Tests

ANTI-HCV (HCV ANTIBODY)

• Measures antibody response to virus.
• 2nd and 3rd generation tests with confirmatory test are generally quite accurate but still have a low false positive rate..
• Antibody levels indicate the positivity of the test (ie level above cutoff) but are no guide to the severity of hepatitis.

LIVER ENZYMES

• ALT is the best indicator of hepatitis.
• Commonly fluctuates in HCV.
• If consistently normal (with positive anti-HCV and negative HCV-RNA) may suggest resolved past exposure.

VIRAL SUBTYPES

PCR (POLYMERASE CHAIN REACTION)

• A sensitive technique for detecting viral RNA.
• Even small amounts of RNA can be amplified and detected.
• Is a marker of viral replication and infectivity if positive.
• The commonly available test gives a non-qualitative result (ie. detected or not detected).
• The test is not currently funded under Medicare and costs about $60.

• If the anti-HCV and confirmatory test are equivocal and the ALT consistently normal, a negative PCR strongly suggests that the patient does not have hepatitis C.
• If a patient has normal LFTs during Interferon therapy but has a positive PCR 6-12 months into therapy, they are likely to relapse when therapy ceases.
• If the anti-HCV test is positive and the ALT consistently normal, and the PCR negative on two occasions over six to 12 months, then the patient has probably recovered after past infection.
• If the patient has several possible causes for liver disease and is anti-HCV positive, a positive PCR suggests that HCV is playing a role in the liver disease.

TEST	RESULTS	INTERPRETATION	RECOMMENDATION
anti-HCV	positive	chronic hepatitis, chronic hepatitis C recovered, recent acute hepatitis C, or false positive test	further evaluation
anti-HCV ALT EIA	positive normal positive	possible chronic HCV or recovered infection	further evaluation
anti-HCV ALT EIA	positive elevated positive	presume chronic hepatitis C	further evaluation/ consider Interferon therapy
anti-HCV ALT EIA	positive normal negative or indeterminate	presume false positive anti-HCV or recovered	further evaluation by HCV-RNA PCR test
anti-HCV ALT EIA	positive elevated negative	presume false positive anti-HCV, false negative supplemental test unlikely	further evaluation for liver disease other then hepatitis C + HCV RNA PCR
ALT (no other +ve tests)	elevated	other liver diseases	further evaluation

Definitions:

• anti-HCV - antibody to hepatitis C virus.
• ALT - Liver enzyme released from liver cells that are injured, eg. by virus, alcohol, fat, drug, etc.
• Indeterminate means one of four antigens positive.
• HCV-RNA test by polymerase chain reaction (PCR) determines whether the virus is multiplying.
• EIA - Elisa immune assay - Supplemental test to detect antibody to hepatitis C virus.

Post Test Counselling

• A positive result often causes psychological trauma and this may be reduced by appropriate counselling at the time of diagnosis.

Counselling issues

Present or past IDU - a sensitive issue
Many people testing positive for HCV have a history of injecting drug use. This may have been years in the past when they dabbled in drugs, perhaps only on one occasion. Their partners and family may be unaware of this and for many it is a sensitive issue.

HCV patients may experience discrimination
HCV is often associated with injecting drug use, and for this reason many patients who are HCV positive have experienced discrimination from their health care providers and from family and friends who may have fears about the spread of HCV. HCV positive patients are not a homogeneous group, either in their mode of contracting the disease, their lifestyles or their socio-economic status, and counselling should be appropriate for the individual. HCV sufferers deserve optimum health care, whether they have an IDU history or not.

Fear of disclosure
Fear of discrimination may lead to social isolation, stress and depression and many patients fear disclosure. Issues of confidentiality should be discussed with the patient.

Fear of the effects of the disease on health and earning capacity
Patients are concerned about the pathological effects of HCV on their well-being and their earning capacity. It is important that the natural history of the disease, the symptomatology and the significance of test results are carefully explained. Patients need to be supplied with up to date information about HCV and treatment options.

Frustration with not knowing health status
Many patients express frustration at not knowing their health status. This has been compounded in the past by false positive antibody tests, an inability to readily identify those who have been exposed but who do not have progressive disease, inadequate research and education of health care providers.

Support in decision making about medical intervention and starting antiviral therapy
Full explanations about the advantages, limitations and side effects of antiviral therapy allow the patient to make an informed choice about treatment options.

Fears about the effect of their disease on their partners and family
Patients are fearful of having transmitted HCV to their partners and their children. They also worry about the effect it may have on their sexual relationships and the dangers of mother to child transmission. To date, hepatitis C RNA has not been isolated in body fluids such as saliva, semen and vaginal secretions. There is no definite evidence that HCV is transmitted by sharing of cups or utensils or through social contact. Studies based on serological screening of sexual partners and household contacts of HCV infected patients suggest that sexual transmission is infrequent. The risks through pregnancy, sexual relationships and household contacts should be clearly outlined. Testing should be offered to partners and children.

Information on legal issues

• legal requirements of reporting positive results
• disclosure of HCV and discrimination
• confidentiality requirements

The Hepatitis C Council of NSW
The Hepatitis C Council is an independent community based organisation. It provides a telephone information, support and referral service and produces and distributes information booklets, brochures, videos and a newsletter.

Counselling for patients with negative results
Those with negative results should be counseled for at risk behavior. They may need repeat testing to take into account the window period.

Lifestyle Changes

Hepatitis C may cause gastrointestinal symptoms such as loss of appetite, nausea, reflux or diarrhoea, which may contribute to nutrient deficiency. Fatty foods often increase gastrointestinal symptoms. Diet should be tailored to the patient's needs and the severity of the disease.

Reduce alcohol intake to 1 standard drink per day. If this is impossible:

• use low alcohol drinks
• avoid binge drinking

Prescribed drugs

• Do not donate blood or other tissue
• Do not share needles or any other injecting equipment
• Advise health care workers and dentists of HCV status
• Do not share toothbrushes, razors and other personal articles
• Wipe up blood spills with bleach and paper towels
• Cover cuts and wounds with waterproof dressings
• Dispose of blood stained articles in a plastic bag before placing in the garbage
• Practice safe sex avoiding blood contact during intercourse (during menstruation, with coexistent STDs or traumatic intercourse). Condoms should always be used for anal intercourse. There is no evidence that HCV is transmitted by kissing.

Counselling IDUs

AVOIDANCE OF ILLICIT DRUG USE - While this is the preferred option it may not be the choice of the patient. Advice should be given about drug and alcohol counselling, and detox and rehabilitation facilities. Information about local methadone clinics and prescribers should be offered.

CHANGE TO ROUTES OTHER THAN PARENTERAL - Although the same dose may have a slower and reduced effect, smoking, snorting or taking drugs orally carries a much lower risk of infection.

REDUCE RISKS IF USING INTRAVENOUSLY - Needles, syringes and other users' equipment should not be shared. This includes avoiding sharing needles, syringes, swabs, filters, spoons, water, utensils and tourniquets. Information about local needle exchanges and safe disposal of needles should be offered.

IF SHARING NEEDLES, REDUCE RISK BY CLEANING IN BLEACH - This is not very effective at killing the HCV virus but does reduce the risk of transmission.

SHARING NEEDLES WITH SOMEONE ELSE WITH HEP C IS NOT SAFE - Being HCV antibody positive does not protect a patient from reinfection. A person who has contacted HCV and does not have active disease may become infected with the same or another genotype. A person with active disease may become coinfected by another genotype and develop more severe disease. Different genotypes are associated with varying severity of disease, infectivity and response to antiviral therapy.

SAFE DISPOSAL OF NEEDLES - This is vital to the prevention of spread of HCV.

Counselling IDUs about hep C is vital, not only for their own sakes, but to prevent the further spread of this disease which is already a major public health problem.

Assessing the Disease

Symptoms

• fatigue, lethargy and need to sleep for long periods
• waking up feeling tired
• nausea
• right upper quadrant pain
• sweating

• Commonly have no abnormal signs
• Multiple spider naevi are commonly seen
• Cirrhosis may be undetectable clinically
• Patients may have typical signs of chronic liver disease
  • palmar erythema
  • spider naevi
  • jaundice
  • gynaecomastia
  • hepatosplenomegaly
  • ascites, oedema and complications including variceal bleeding, liver failure, spontaneous bacterial peritonitis and hepato cellular carcinoma.

Treatment Options

INTERFERON

Interferon Alfa is a relatively expensive treatment. On current costings, the 12 month cost of the drug alone is about $3,000. The Federal Government will fund Interferon Alfa under Section 100 of the National Health Act for patients with chronic hep C who satisfy the following criteria.

GPs are asked to assess patients carefully with regard to the following criteria, prior to specialist referral for Interferon treatment

Have chronic hepatitis evident in liver biopsy, except in patients with coagulation disorder; Have positive anti-HCV antibody on repeated testing, tested twice over six months with an interval of at least 16 weeks; There is no cirrhosis or other liver disease; There is no HIV infection (HIV Ab-ve/patient consent required); Are not pregnant, lactating or not practising an adequate form of birth control; Have no history of significant psychiatric illness; Would be likely to attend regularly for treatment and follow-up; Drink no more that seven standard drinks a week; Have not used illicit injectable drugs within the previous twelve months; The course of treatment is limited to three million units subcutaneously three times weekly for 12 months; If the ALT remains greater than the upper limit of the laboratory reference range after twelve weeks, treatment is to cease.

It is important to highlight that the patient requires three above normal ALT levels over a six month period. Patients being referred for consideration of liver biopsy and Alfa Interferon should have undergone such testing.

There is a current requirement for liver biopsy. There is an exemption for patients with coagulation disorders. The rationale for liver biopsy is to determine the presence or absence of cirrhosis, the activity of the hepatitis and to exclude coexistent liver disease. You will note that the upper limit of alcohol use is specified and the patient should not have used illicit injectable drugs within the previous 12 months.

A history of significant psychiatric illness is listed as a contraindication. The major concern is mood disorders, particularly depressive illness, as the exacerbation or triggering of moderate to severe depression can occur on Interferon therapy. Many patients with hep C show anxiety and other relatively minor psychiatric disorders but these do not normally preclude use of this drug.

Understandably many patients are concerned by the need to inject the drug. Interferon Alfa is a protein or polypeptide and is digested in the stomach and proximal small intestine. In this regard it is similar to insulin, requiring a parenteral route of administration. Most patients can be taught to self inject by the GP or the general practice nurse. Usual sites of injection are the anterior abdominal wall or the thighs, with the injection being a subcutaneous injection. Needles, syringes and alcohol wipes as well as instructions are provided with the supply of Interferon.

Many patients are concerned about the side effects of Interferon. These can be classified as short term or long term.
Short term side effects
The short term side effects usually subside within the first week or two of treatment. They normally occur within four to six hours of the first few injections and can be reduced to a tolerable level by prophylactic use of Paracetamol. These side effects are fever, aches and chills, flu-like symptoms.

Medium to long term side effects
The medium to long term side effects whilst on treatment are fatigue, alteration in mood, sleep disturbance, suppression of white cell count and platelet count, reduction in appetite and weight, dryness of the mucous membranes and hair loss. These side effects are rarely serious enough to require alteration in dose or cessation of treatment.

For those patients undergoing antiviral therapy, the patient would see the specialist at the end of the first, third, fifth, seventh, ninth and eleventh months with the patients seeing the GP at the end of the second, fourth, sixth, eighth, tenth and twelfth months. A patient history, examination, assessment of effects of treatment, liver function tests and full blood count would be performed at each visit with the data collated for the National Hepatitis C Data Bank. The decision to continue with treatment at the three month point is made on the basis of normalisation of the ALT levels at that time.

Interferon Alfa is not a panacea for hep C infection. It currently represents the only effective treatment, but unfortunately the majority of patients will not have a long term response. There is a considerable research effort throughout the world to find other antiviral therapies. Ribaviron may soon enter clinical practice.

SHARED CARE PROGRAMME FOR INTERFERON

Adam Osborne, a local GP, experienced in the use of TCM, outlines his approach to hep C.

The liver has been dubbed 'the Bandit of a Thousand Illnesses' in Traditional Chinese Medicine (TCM) because of the many different types of symptoms to which its ills give rise. Although most authorities agree there are four main patterns of hep C sufferers in TCM, there are many different symptoms attributed to hep C including diarrhoea, nausea, sub-costal pain, tiredness and so on. This recognises that different individuals respond in a different way to the same infectious organism. In TCM a patient's condition is characterised by the total set of symptoms, together with the clinical signs (general appearance, body structure, tongue appearance and palpative quality of the radial pulse). Commonly observed patterns of symptoms and signs in science are given descriptive labels for convenience. Armed with this description, herbs and herbal formulas that have been shown to be effective in counteracting the specific pattern are chosen. These clinical signs and symptoms have been systematised over 5,000 years of observation and recording. Although hep C has only recently been diagnosed, hepatitis of various types has been successfully treated for hundreds of years with herbal medicines in China that in effect 'clear out the liver'. These are dispensed as pills, powder or the dried herbs which are decocted and taken as a tea. When people first come to me, I test their LFT, and suggest ultra sound, biopsy or specialist referral as applicable. I then prescribe a six to 12 month programme of the herbs depending on their degree of illness and stage of the disease. I have found that most patients get relief of presenting symptoms within a couple of weeks, but ideally treatment continues for six to 12 months. The herbs can be taken with Interferon although I don't recommend this if people are taking part in a clinical trial. The role of diet in prognosis is contentious, but I give patients dietary guidelines because their digestive system is weakened by the liver not smoothly distributing blood to it. They are adversely affected by oily or deep fried foods, hot spices, alcohol and smoking. Easily digested foods are better tolerated and assist the patient's wellbeing. TCM believes the liver is the 'seat of emotion' and in my experience sufferer's symptoms worsen with stress, emotional and psychological upset. In a sedentary lifestyle the liver's function in moving blood smoothly to the organs and digestive system can stagnate. This process of stagnation of blood movement by the liver can also come about through psychological inaction such as suppression or repression of emotions. Newly diagnosed patients with hep C have often had the disease for a decade or more. In my experience a holistic approach using TCM enables their process to recovery. ~ Adam Osborne

Monitoring disease progress

In the stable patient who does not wish to consider antiviral therapy (Interferon) or who has failed antiviral therapy, the following is recommended:

• 4 monthly clinical review by GP with reassessment of symptoms, signs and LFTs as well as continuing education and psychologic support.
• Alfa feta protein and hepatobiliary ultrasound yearly in the cirrhotic patient.

Liver biopsy

Before the procedure, informed consent, representative liver function tests, full blood count, coagulation studies and hepatobiliary ultrasound are performed. The patient is admitted to hospital in the morning, having fasted from midnight. Premedication can be given as required by the patient.

The procedure is usually performed in a radiology department, with ultrasound assistance to increase the margin of safety. The right infero-lateral aspect of the chest is the most usual position, along the mid axillary line. The skin is disinfected, local anaesthetic installed in stages to the skin, muscle and surface of the liver until analgesia is obtained. A 16 or 18 gauge needle is then passed between the intercostal space for an average distance of 5cm into the parenchyma of the right lobe of the liver. A thin core of tissue is then obtained, the patient is asked to lie on their right hand side for four hours and frequent observations taken.

About 50 percent of patients will require post-operative analgesia which may be in the form of Paracetamol and Codeine or narcotic. Patients may start fluids four hours later and are usually discharged eight hours later. Patients who live more than half an hour from the hospital are often admitted overnight for observation.

Liver biopsy is a safe procedure. The potential complications are hemorrhage from the surface of the liver or an intercostal vessel, perforation of a major bile radical or the gall bladder, pneumothorax, colonic perforation and local infection. The risk of a major complication is in the order of 1/1000. In the presence of continued bleeding from the surface of the liver, major bile leak or gall bladder perforation or colonic perforation, a laparotomy may be required. Death is a remote possibility.

Understandably the majority of patients are concerned by having an invasive test. While the procedure is not risk free, by far the majority of patients will have an uneventful liver biopsy. They will all experience at least minor pain but with reassurance and sensible use of post-procedure analgesia, the majority of patients remark that it was much better than expected.

Liver transplantation is of course a major physical and psychological undertaking and is reserved for patients with severe impairment of quality of life or impending death from their liver disease. One year survival after transplant is about 80%. The grafted liver will always become reinfected and for the majority of patients, liver transplant will represent a bridge, to allow them to survive and function until successful and eradicative antiviral therapy can be given.

Resources

Recommended Further Reading

Overview

The OBSVIRC, METAVIR, CLINIVIR, and DOSCVIR groups. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349(9055): 852-32

Kaldor JM, Archer GT, Burning ML, et al., Risk factors for hepatitis C virus infection in blood donors: a case-control study. Med J Aust 1992;157:227-230.

Transmission through Receipt Blood products
Ismay SL, Thomas S, Fellows A, et al., Post-transfusion hepatitis revisited. Med J Aust 1995;163:74-77.

Leslie DE, Rann S, Nicholson S, et al., Prevalence of hepatitis C antibodies in patients with clotting disorders in Victoria. Med J Aust 1992;156:789-792.

Risk of Tattooing
Ko Y-C, Ho M-S, Chang T-A, et al., Tattooing as a risk of hepatitis C virus infection. J Med Virol 1992;38:288-291.

Risk in Prison inmates
Crofts N, Stewart T, Hearne P, et al., Spread of blood-borne viruses among Australian prison entrants. Br Med J 1995;310:285-88.

Sexual Transmission
Scaraggi FA, Lomuscio S, Perricci A, et al., Intrafamilial and sexual transmission of hepatitis C virus. BMJ 1993;342:1300-1301.

Bresters D, Mauser-Brunschoten EP, Reesink HW, et al., Sexual transmission of hepatitis C virus. Lancet 1993;342:210-211.

Thomas DL, Zenilman JM, Alter HJ, et al., Sexual transmission of hepatitis C virus among patients attending sexually transmitted diseases clinics in Baltimore - An analysis of 309 sex partnerships. J Infect Dis 1995;171:768-75.

Transmission to Health Care Workers
Lanphear BP. Trends and patterns in the transmission of bloodborne pathogens to health care workers. Epidemiol. Reviews 1994;16:1109-1114.

Gerberding JL. Incidence and prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus and cytomegalovirus among health care personnel at risk for blood exposure: Final report from a longitudinal study. J Infect Dis 1994;170:1410-7.

Transmission from Mothers to Infants
Ohto H, Terazawa S, Sasaki N, et al., Transmission of hepatitis C virus from mothers to infants. New Engl J Med 1994;330:744-750.

Lin H-H, Kao J-H, Hsu H-Y, et al., Possible role of high-titre maternal viraemia in perinatal transmission of hepatitis C virus. J Inf Dis 1994;169:638-641.

Zanetti AR, Tanzi E, Paccognini S, et al., Mother-to-infant transmission of hepatitis C virus. Lancet 1995;345:289-91.

Transmission through IDU
Kaldor JM, Archer GT, Buring ML, et al., Risk factors for hepatitis C virus infection in blood donors: a case-control study. Med J Aust 1992;157:227-230.

Crofts N, Hooper JL, Bowden DS, Breschkin AM, Milner R, Locarnini SA, Hepatitis C virus infection among a cohort of Victorian injecting drug users. Med J Aust 1993;159(4):237-41.

Van Beek I, Buckley R, Stewart M, MacDonald M, Kaldor J, Risk factors for hepatitis C virus infection among injecting drug users in Sydney. Genitourin Med 1994;70(5):321-4.

Response to Interferon treatment
Bellary S, Smith DG, Bankers P, Harris A Shayiq R, Black M, High dose Interferon alpha-2B therapy for chronic hepatitis C: an open label study of the response and predictors of response. Am J Gastrenterol 1995 Feb; 90(2):259-62.

Davis GI, Balart LA, Schiff ER, et al., Treatment of chronic hepatitis C with recombinant Interferon alpha. A multi-centre randomised controlled trial. N Engl J Med 1989;321:1501-1506. Poynard et al. Meta-analysis of Interferon randomised trials in the treatment of viral hepatitis C: effects of dose and duration. Hepatology 1996; 24(4) 778-89.

Genotype and response to Interferon
Swanson NR, Lareu RR, Reed WD, Fox SA. An analysis of the influence of HCV genotype on short and long-term responses to alpha Interferon therapy for chronic hepatitis C. Hepatology. 1994; 20:157a.

HCV RNA load & response to Interferon
Lin R, Liddle C, Farrell GC, HCV RNA load is predictive of long-term response to Interferon treatment in patients with chronic hepatitis C. Hepatology, 1994;20:157a.

"Hepatitis C. Ten Questions and Answers". CEIDA Publication 1994.

"Hepatitis C Second Edition". Australian Gastroenterology Institute 1994.

"Hep C What you need to know". Hep C Council of NSW.

List of Agencies

Information and Support Services

Local Health Services

Methadone Prescribers

Acknowledgements

I would like to thank Drs Mark Cornwell, Howard Hope and Adam Osborne for their input into this manual, the Public Health Unit, Katherine Breen Kurucsev at the Northern Rivers Division of General Practice for journalistic support and to Professor Bob Batey for proof reading.

Dr Jane Barker