Hepatitis C

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Overview

Hepatitis C
ICD-10	B17.1, B18.2
ICD-9	070.4, 070.5
OMIM	609532
DiseasesDB	5783
MedlinePlus	000284
eMedicine	med/993
MeSH	D006526

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This page is for the disease. For the virus, see Hepatitis C virus.

Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called Hepatitis C virus (HCV). The infection can cause liver inflammation (hepatitis) that is often asymptomatic, but ensuing chronic hepatitis can result later in cirrhosis (fibrotic scarring of the liver) and liver cancer.

The hepatitis C virus (HCV) is spread by blood-to-blood contact with an infected person's blood. The symptoms can be medically managed, and a proportion of patients can be cleared of the virus by a long course of anti-viral medicines. Although early medical intervention is helpful, people with HCV infection often experience mild symptoms, and consequently do not seek treatment. An estimated 150-200 million people worldwide are infected with hepatitis C. In the U.S., those with a history of intravenous drug use, inhaled drug usage, tattoos, or who have been exposed to blood via unsafe sex or social practices are increased risk for this disease. Hepatitis C is the leading cause of liver transplant in the United States.

The Virus

Main article: Hepatitis C virus

The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus in the families Flaviviridae.

History

In the mid 1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health (NIH), and his research team demonstrated that most post-transfusion hepatitis cases were not due to hepatitis A and B viruses. Despite this discovery, international research effort to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation utilized molecular cloning to identify the unknown organism. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April of 1989, the discovery of the virus, re-named hepatitis C virus (HCV), was published in two articles in the journal Science.

Dr. D.W. Bradley filed suit against Chiron, challenging the status of U.S. patent 5,350,671 covering HCV clones, diagnostics, and vaccines. Dr. Bradley sought to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income from Chiron. Dr. Bradley claimed he supplied Chiron with HCV-infected plasma that was instrumental in Chiron's isolation and cloning of HCV, that he developed critical findings about the virus, and that he provided Chiron with assistance regarding cloning methods. Dr. Bradley began work on what was then called non-A, non-B hepatitis in 1977 and the dispute between Dr. Bradley and Chiron can be traced back to 1986 when the parties failed to agree on terms for Dr. Bradley to provide infected plasma to Chiron.

Epidemiology

Hepatitis C infects an estimated 170 million people worldwide and 4 million in the United States. There are about 35,000 to 185,000 new cases a year in the United States. Co-infection with HIV is common and rates among HIV positive populations are higher. 10,000-20,000 deaths a year in the United States are from HCV; expectations are that this mortality rate will increase, as those who were infected by transfusion before HCV testing become apparent. A survey conducted in California showed prevalence of up to 34% among prison inmates; 82% of subjects diagnosed with hepatitis C have previously been in jail, and transmission while in prison is well described.

Egypt has the highest seroprevalence for HCV, up to 20% in some areas. There is a hypothesis that the high prevalence is linked to a now-discontinued mass-treatment campaign for schistosomiasis, which is endemic in that country.

Risk Factors

• Intravenous drug users (IVDU)
• Blood transfusion before 1990

  • Current transfusion-associated risk: < 1/100,000
  • Comparative risks: Hepatitis B Virus (HBV) 1/63,000, HIV 1/493,000
  • Residual risk due to recently infected donors (10 week window)

• Percutaneous exposures

  • Needle stick transmission: ~3% HCV, 30% HBV, 0.3% HIV

• Lesser Risk Factors

  • High-risk sexual behavior
  • Low socioeconomic status (unclear mechanisms)

    • Sexual transmission inefficient
    • HIV coinfection increases sexual and maternal-fetal transmission

• Risk Factors For Progression

  • EtOH use
  • HIV or HBV coinfection
  • Older age at infection, male sex

• Number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004.
• Most infections are due to illegal injection drug use.
• Transfusion-associated cases occurred prior to blood donor screening; now occurs in less than one per 2 million transfused units of blood.
• Estimated 4.1 million (1.6%) Americans have been infected with HCV, of whom 3.2 million are chronically infected.
• The risk for perinatal HCV transmission is about 4%
• If coinfected with HIV the risk for perinatal infection is about 19%

Transmission

CDC figures for sources of infection in the US. Source

The hepatitis C virus (HCV) is transmitted by blood-to-blood contact. In developed countries, it is estimated that 90% of persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via injecting drug use or by inhalational drug use. In developing countries, the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood products.

Although injection drug use and receipt of infected blood/blood products are the most common routes of HCV infection, any practice, activity, or situation that involves blood-to-blood exposure can potentially be a source of HCV infection. The virus may be sexually transmitted, although this is rare, and usually only occurs when a second STD makes blood contact more likely.

Methods of transmission

Several activities and practices have been identified as potential sources of exposure to the hepatitis C virus. Anyone who may have been exposed to HCV through one or more of these routes should be screened for hepatitis C.

Injection drug use

Those who currently or have used drug injection as their delivery route for illicit drugs are at increased risk for getting hepatitis C because they may be sharing needles or other drug paraphernalia (includes cookers, cotton, spoons, water, etc.), which may be contaminated with HCV-infected blood. An estimated 60% to 80% of all IV drug users in the United States have been infected with HCV. Harm reduction strategies are encouraged in many countries to reduce the spread of hepatitis C, through education, provision of clean needles and syringes, and safer injecting techniques.

Drug use by nasal inhalation (Drugs which are "snorted")

Researchers have suggested that the transmission of HCV may be possible through the nasal inhalation (insuffulation) of illegal drugs such as cocaine and crystal methamphetamine when straws (containing even trace amounts of mucus and blood) are shared among users.

Blood products

Blood transfusion, blood products, or organ transplantation prior to implementation of HCV screening (in the U.S., this would refer to procedures prior to 1992) is a decreasing risk factor for hepatitis C.

The virus was first isolated in 1989 and reliable tests to screen for the virus were not available until 1992. Therefore, those who received blood or blood products prior to the implementation of screening the blood supply for HCV may have been exposed to the virus. Blood products include clotting factors (taken by hemophiliacs), immunoglobulin, Rhogam, platelets, and plasma. In 2001, the Centers for Disease Control and Prevention reported that the risk of HCV infection from a unit of transfused blood in the United States is less than one per million transfused units.

Iatrogenic; medical or dental exposure

People can be exposed to HCV via inadequately or improperly sterilized medical or dental equipment. Equipment that may harbor contaminated blood if improperly sterilized includes needles or syringes, hemodialysis equipment, oral hygiene instruments, and jet air guns, etc. Scrupulous use of appropriate sterilization techniques and proper disposal of used equipment can reduce the risk of iatrogenic exposure to HCV to virtually zero.

Occupational exposure to blood

Medical and dental personnel, first responders (e.g., firefighters, paramedics, emergency medical technicians, law enforcement officers), and military combat personnel can be exposed to HCV through accidental exposure to blood through accidental needlesticks or blood spatter to the eyes or open wounds. Universal precautions to protect against such accidental exposures significantly reduce the risk of exposure to HCV.

Recreational exposure to blood

Contact sports and other activities, such as "slam dancing" that may result in accidental blood-to-blood exposure are potential sources of exposure to HCV.

Sexual exposure to blood

Sexual transmission of HCV is considered to be rare. The CDC does not recommend the use of condoms between discordant couples (where one partner is positive and the other is negative); however, because of the high prevalence of hepatitis C, this small risk may translate into a non-trivial number of cases transmitted by sexual routes. Vaginal penetrative sex is believed to have a lower risk of transmission than sexual practices that involve higher levels of trauma to anogenital mucosa (anal penetrative sex, fisting, use of sex toys).

Body piercings and tattoos

Tattooing dyes, ink pots, stylets and piercing implements can transmit HCV-infected blood from one person to another if proper sterilization techniques are not followed. Tattoos or piercings performed before the mid 1980s, "underground," or non-professionally are of particular concern since sterile techniques in such settings may have been or be insufficient to prevent disease.

Shared personal care items

Personal care items such as razors, toothbrushes, cuticle scissors, and other manicuring or pedicuring equipment can easily be contaminated with blood. Sharing such items can potentially lead to exposure to HCV.

HCV is not spread through casual contact such as hugging, kissing, or sharing eating or cooking utensils.

Vertical transmission

Vertical transmission refers to the transmission of a communicable disease from an infected mother to her child during the birth process. Mother-to-child transmission of hepatitis C has been well described, but occurs relatively infrequently. Transmission occurs only among women who are HCV RNA positive at the time of delivery; the risk of transmission in this setting is approximately 6 out of 100. Among women who are both HCV and HIV positive at the time of delivery, the risk of HCV is increased to approximately 25 out of 100.

The risk of vertical transmission of HCV does not appear to be associated with method of delivery or breast feeding.

Co-infection with HIV

Approximately 350,000, or 35% of patients in the USA infected with HIV are also infected with the hepatitis C virus, mainly because both viruses are blood-borne and present in similar populations. In other countries co-infection is less common, and this is possibly related to differing drug policies. HCV is the leading cause of chronic liver disease in the USA. It has been demonstrated in clinical studies that HIV infection causes a more rapid progression of chronic hepatitis C to cirrhosis and liver failure. This is not to say treatment is not an option for those living with co-infection.

Diagnosis

The diagnosis of "hepatitis C" is rarely made during the acute phase of the disease because the majority of people infected experience no symptoms during this phase of the disease. Those who do experience acute phase symptoms are rarely ill enough to seek medical attention. The diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the disease.

Chronic hepatitis C may be suspected on the basis of the medical history (particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoos, unexplained symptoms, or abnormal liver enzymes or liver function tests found during routine blood testing. Occasionally, hepatitis C is diagnosed as a result of targeted screening such as blood donation (blood donors are screened for numerous blood-borne diseases including hepatitis C) or contact tracing.

Hepatitis C testing begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong positive predictive value for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion), or have an insufficient level of antibodies to detect. While uncommon, a small minority of people infected with HCV never develop antibodies to the virus and therefore, never test positive using HCV antibody screening.

Anti-HCV antibodies indicate exposure to the virus, but cannot determine if ongoing infection is present. All persons with positive anti-HCV antibody tests must undergo additional testing for the presence of the hepatitis C virus itself to determine whether current infection is present. The presence of the virus is tested for using molecular nucleic acid testing methods such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only whether the virus is present, but also to measure the amount of virus present in the blood (the HCV viral load). The HCV viral load is an important factor in determining the probability of response to interferon-based therapy, but does not indicate disease severity nor the likelihood of disease progression.

In people with confirmed HCV infection, genotype testing is generally recommended. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.). HCV genotype testing is used to determine the required length and potential response to interferon-based therapy.

Signs and symptoms

Early studies of viral loads in eleven asymptomatically infected viral carriers (blood donors in 1989, prior to implementation of blood bank screening for HCV, and from whom the donated blood units were rejected because of elevated alanine transaminase (ALT) liver enzyme levels) indicated that asymptomatic viral loads in blood plasma varied between 100/mL and 50,000,000/mL.

80% of persons have no signs or symptoms. General symptoms include:

• jaundice
• fatigue
• dark urine
• abdominal pain
• loss of appetite
• nausea

Clinical Findings According to Disease Stages

• Acute

  • Mild or absent symptoms (7-8 weeks after exposure)

• Chronic

  • Fatigue

• Late Complications

  • Cirrhosis
  • Hepatocellular carcinoma (HCC) in cirrhotics (1-4%/year)

• Extrahepatic Symptoms

  • Cryoglobulinemia (~50%)

    • Only 10-15% of patients with +cryos have symptoms
    • Symptoms

      • Arthralgias
      • Weakness
      • Purpura
      • Membranoproliferative glomerulonephritis (MPGN)

  • Pruritus, psoriasis, Raynaud’s phenomenon (6-20%)
  • Sicca syndrome (10-12%)
  • Neuropathy (5-9%)
  • Porphyria cutanea tarda (PCT), lichen planus (1%)

Laboratory Diagnosis

• HCV Enzyme-linked immunosorbent assay (ELISA)

  • Positive within 4-10 weeks after infection
  • False negatives can occur with HIV infection, chronic renal failure, cryos

• HCV RNA

  • Polymerase chain reaction (PCR) highly sensitive for confirming viremia
  • Predicts response to therapy but not risk of progression

There are several blood tests that can be done to determine if you have been infected with HCV. Your doctor may order just one or a combination of these tests. The following are the types of tests your doctor may order and the purpose for each:

a) Anti-HCV (antibody to HCV)

EIA (enzyme immunoassay) or CIA (enhanced chemiluminescence immunoassay) Test is usually done first. If positive, it should be confirmed

RIBA (recombinant immunoblot assay) A supplemental test used to confirm a positive EIA test

Anti-HCV does not tell whether the infection is new (acute), chronic (long-term) or is no longer present.

b) Qualitative tests to detect presence or absence of virus (HCV RNA)

c) Quantitative tests to detect amount (titer) of virus (HCV RNA)

A single positive PCR test indicates infection with HCV. A single negative test does not prove that a person is not infected. Virus may be present in the blood and just not found by PCR. Also, a person infected in the past who has recovered may have a negative test. When hepatitis C is suspected and PCR is negative, PCR should be repeated.

Clinical Stages

Acute Hepatitis C

Acute hepatitis C refers to the first 6 months after infection with HCV. Between 60% to 70% of people infected develop no symptoms during the acute phase. In the minority of patients who experience acute phase symptoms, they are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.

The hepatitis C virus is usually detectable in the blood within one to three weeks after infection, and antibodies to the virus are generally detectable within 3 to 12 weeks. Approximately 20-30% of persons infected with HCV clear the virus from their bodies during the acute phase as shown by normalization in liver function tests (LFTs) such as alanine transaminase (ALT) & aspartate transaminase (AST) normalization, as well as plasma HCV-RNA clearance (this is known as spontaneous viral clearance). The remaining 70-80% of patients infected with HCV develop chronic hepatitis C, i.e., infection lasting more than 6 months.

Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate with half the treatment time required for chronic infections, but that the majority of acute hepatitis C is cleared.

Chronic Hepatitis C

Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic (without jaundice) and it is mostly discovered accidentally.

The natural course of chronic hepatitis C varies considerably from one person to another. Virtually all people infected with HCV have evidence of inflammation on liver biopsy, however, the rate of progression of liver scarring (fibrosis) shows significant variability among individuals. Recent data suggests that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years. Another third progress to cirrhosis within 30 years. The remainder of patients appear to progress so slowly that they are unlikely to develop cirrhosis within their lifetimes. Factors that have been reported to influence the rate of HCV disease progression include age (increasing age associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an increased rate of disease progression).

Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, marked weight loss, flu-like symptoms, muscle pain, joint pain, intermittent low-grade fevers, itching, sleep disturbances, abdominal pain (especially in the right upper quadrant), appetite changes, nausea, diarrhea, dyspepsia, cognitive changes, depression, headaches, and mood swings.

Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension. Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen), bruising and bleeding tendency, bone pain, varices (enlarged veins, especially in the stomach and esophagus), fatty stools (steatorrhea), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.

Liver function tests show variable elevation of ALAT, AST and GGTP and periodically they might show normal results. Usually prothrombin and albumin results are normal. The level of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies such as ultrasound or CT scan do not show liver injury until it is fairly advanced.

Chronic hepatitis C, more than other forms of hepatitis, is diagnosed because of extrahepatic manifestations associated with the presence of HCV such as thyroiditis (inflammation of the thyroid) with hyperthyreosis or hypothyreosis, porphyria cutanea tarda, cryoglobulinemia (a form of vasculitis) and glomerulonephritis (inflammation of the kidney), specifically membranoproliferative glomerulonephritis (MPGN) . Hepatitis C is also associated with sicca syndrome, thrombocytopenia, lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders.

Differential Diagnosis

• Viral Hepatitis A
• Viral Hepatitis B
• Viral Hepatitis C
• Viral Hepatitis D
• Viral Hepatitis E

Treatment

Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment (but balance this against the 80% chance of spontaneous clearance without treatment).

Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 2 million virons/ml). Current combination therapy is usually supervised by physicians in the fields of gastroenterology, hepatology or infectious disease.

The treatment may be physically demanding, particularly those with a prior history of drug or alcohol abuse. It can qualify for temporary disability in some cases. A substantial proportion of patients will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including anemia, cardiovascular events and psychiatric problems such as suicide or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.

In addition to the standard treatment with interferon and ribavirin, some studies have shown a higher success rates when the antiviral drug amantadine (Symmetrel) is added to the regimen. Sometimes called "triple therapy", it involves the addition of 100mg of amantadine twice a day. Studies indicate that this may be especially helpful for "nonresponders" - patients who have not been successful in previous treatments using interferon and ribavirin only. Currently, amantadine is not approved for treatment of Hepatitis C, and studies are ongoing to determine when it is most likely to benefit the patient. Followup studies have shown no benefit to adding this drug and currently it is not commonly used by experienced hepatologists.

Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not yet been exposed to these viruses, as this would radically worsen their liver disease.

Alcoholic beverage consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; insulin resistance and metabolic syndrome may similarly worsen the hepatic prognosis. There is also evidence that smoking increases the fibrosis (scarring) rate.

Treatment Indications

• Clearly Indicated

  • Detectable HCV RNA and persistently elevated alanine aminotransferase (ALT)
  • Liver biopsy with fibrosis or moderate necrosis/inflammation

    • High risk disease progression

• Possibly Beneficial

  • Detectable HCV RNA and elevated ALT
  • Liver biopsy with minimal or mild inflammatory changes

    • Lower risk disease progression
    • Alternative = follow ALT and re-biopsy at 3-5 years

• Not Indicated

  • Detectable HCV RNA with persistently normal ALT
  • Liver biopsy with minimal or no inflammatory changes

    • Excellent prognosis without therapy
    • May consider therapy if extrahepatic hepatic manifestations

• Contraindicated

  • IFN-alfa

    • Severe depression, psychosis
    • Decompensated cirrhosis
    • Neutropenia or thrombocytopenia
    • Uncontrolled seizures
    • Organ transplant (other than liver)
    • Symptomatic heart disease

  • Ribavirin

    • Pregnancy or inadequate contraception
    • Anemia, hemoglobinopathy
    • Severe cardiac disease or end-stage renal disease (ESRD)

Chronic Pharmacotherapies

• Interferon alfa monoRx

  • Sustained response 16%
  • Genotype 1a or 1b--lowest response rate

• IFN-alfa + ribavirin

  • Sustained response 40%
  • Genotype 1 or high HCV RNA--max response at 48 weeks
  • Genotype 2 or 3--maximal response at 24 weeks
  • Doses = IFN 3 mU sc tiw + ribavirin 600 mg po bid
  • If HCV RNA+ at 24 weeks, discontinue therapy (no response)

• Pegylated Interferon

  • Higher response rate than conventional IFN monoRx
  • Weight-based dose given every week
  • Combination with ribavirin currently in clinical trials

During pregnancy and breastfeeding

If a pregnant woman has risk factors for hepatitis C, she should be tested for antibodies against HCV. About four out of every hundred infants born to HCV infected women become infected. The virus is spread to the baby at the time of birth. There is no treatment that can prevent this from happening.

In a mother that also has HIV, the rate of transmission can be as high as 19%. There is currently no data to determine whether antiviral therapy reduces perinatal transmission. Ribavirin and interferons are contraindicated during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after rupture of membranes may reduce the risk of transmission to the infant.

HCV antibodies from the mother may persist in infants until 15 months of age. If an early diagnosis is desired, testing for HCV RNA can be performed between the ages of 2 and 6 months, with a repeat test done independent of the first test result. If a later diagnosis is preferred, an anti-HCV test can performed after 15 months of age. Most infants infected with HCV at the time of birth have no symptoms and do well during childhood. There is no evidence that breast-feeding spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are cracked and bleeding.

Alternative therapies

Several "alternative therapies" purport to reduce the liver's duties, rather than treat the virus itself, thereby slowing the course of the disease or keeping the quality of life of the person. As an example, extract of Silybum marianum and licorice are sold for their HCV related effects; the first is said to provide some generic help to hepatic functions, and the second to have a mild antiviral effect and to raise blood pressure.

Experimental treatments

The drug viramidine, which is a prodrug of ribavirin which has better targeting for the liver, and therefore may be more effective against hepatitis C for a given tolerated dose, is in phase III experimental trials against hepatitis C. It will be used in conjunction with interferon, in the same manner as ribavirin. However, this drug is not expected to be active against ribavirin-resistant strains, and the use of the drug against infections which have already failed ribavirin/interferon treatment, is unproven.

There are new drugs under development like the protease inhibitors (including VX 950) and polymerase inhibitors (such as NM 283), but development of these is still in the early phase. One protease inhibitor, BILN 2061, had to be discontinued due to safety problems early in the clinical testing. Some more modern new drugs that provide some support in treating HCV are Albuferon, Zadaxin, and DAPY. Antisense phosphorothioate oligos have been targeted to hepatitis C. Antisense Morpholino oligos have shown promise in preclinical studies and are in a clinical trial. All of these are not approved remedies and have not yet demonstrated their efficacy in clinical trials. Immunoglobulins against the hepatitis C virus exist and newer types are under development. Thus far, their roles have been unclear as they have not been shown to help in clearing chronic infection or in the prevention of infection with acute exposures (e.g. needlesticks). They do have a limited role in transplant patients.

Pathologic Findings

Click on the arrow to view the pathologic findings in viral hepatitis: <youtube v=_hXvbpSxFZw/>

Risk Stratification and Prognosis

• Acute Infection

  • 20% recover
  • 80% have persistent infection

    • 30% of these patients develop cirrhosis

• Genotype

  • Predicts response to treatment
  • Genotype 1 less responsive than types 2 & 3

External links

• CDC's Hepatitis C Fact Sheet
• CDC's Hepatitis C Frequently Asked Questions
• Hepatitis C homepage of the UK National Health Service
• The hepatitis C trust - hepatitis C resource for the UK
• UK Hepatitis C Resource centre - your central referral point for Hepatitis C in the UK
• Special issue on virology and clinical advances of HCV
• National HCV Prison Coalition (U.S.A)
• Hepatitis C Fact Sheet
• Hepatitis C Fact Sheet

Frequently Asked Questions about Hepatitis C

Cirrhosis of the liver and liver cancer may ensue from Hepatitis C.

What is Hepatitis C?

Is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of persons who have the disease. HCV is spread by contact with the blood of an infected person.

Occurs when blood from an infected person enters the body of a person who is not infected. HCV is spread through sharing needles or "works" when "shooting" drugs, through needlesticks or sharps exposures on the job, or from an infected mother to her baby during birth.

Who may have infected?

For example, you may have gotten infected with HCV if:

• you ever injected street drugs, as the needles and/or other drug "works" used to prepare or inject the drug(s) may have had someone else's blood that contained HCV on them.
• you received blood, blood products, or solid organs from a donor whose blood contained HCV.
• you were ever on long-term kidney dialysis as you may have unknowingly shared supplies/equipment that had someone else's blood on them.
• you were ever a healthcare worker and had frequent contact with blood on the job, especially accidental needlesticks.
• your mother had hepatitis C at the time she gave birth to you. During the birth her blood may have gotten into your body.
• you ever had sex with a person infected with HCV.
• you lived with someone who was infected with HCV and shared items such as razors or toothbrushes that might have had his/her blood on them.

Who should get tested for hepatitis C?

• persons who ever injected illegal drugs, including those who injected once or a few times many years ago
• persons who were treated for clotting problems with a blood product made before 1987 when more advanced methods for manufacturing the products were developed
• persons who were notified that they received blood from a donor who later tested positive for hepatitis C
• persons who received a blood transfusion or solid organ transplant before July 1992 when better testing of blood donors became available
• long-term hemodialysis patients
• persons who have signs or symptoms of liver disease (e.g., abnormal liver enzyme tests)
• healthcare workers after exposures (e.g., needle sticks or splashes to the eye ) to HCV-positive blood on the job
• children born to HCV-positive women

What to do during the treatment?

• HCV positive persons should be evaluated by their doctor for liver disease.
• Interferon and ribavirin are two drugs licensed for the treatment of persons with chronic hepatitis C.
• Interferon can be taken alone or in combination with ribavirin. Combination therapy, using pegylated interferon and ribavirin, is currently the treatment of choice.
• Combination therapy can get rid of the virus in up to 5 out of 10 persons for genotype 1 and in up to 8 out of 10 persons for genotype 2 and 3.
• Drinking alcohol can make your liver disease worse.

Treatment is very expensive, how can I find out more information about treatment options?

There is a very small chance of clearing the virus spontaneously (0.5 to 0.74% per year), and the majority of patients with chronic hepatitis C will not clear it without treatment.

Current treatment is a combination of pegylated interferon alpha (brand names Pegasys and PEG-Intron) and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on genotype. Indications for treatment include patients with proven hepatitis C virus infection and persistent abnormal liver function tests. Sustained cure rates (sustained viral response) of 75% or better occur in people with genotypes HCV 2 and 3 in 24 weeks of treatment,about 50% in those with genotype 1 with 48 weeks of treatment and 65% for those with genotype 4 in 48 weeks of treatment. About 80% of hepatitis C patients in the United States have genotype 1. Genotype 4 is more common in the Middle East and Africa. Should treatment with pegylated ribivirin-interferon not return a 2-log viral reduction or complete clearance of RNA (termed early virological response) after 12 weeks for genotype 1, the chance of treatment success is less than 1%. Early virological response is typically not tested for in non-genotype 1 patients, as the chances of attaining it are greater than 90%. The mechanism of action is not entirely clear, because even patients who appear to have had a sustained virological resonse still have actively replicating virus in their liver and peripheral blood mononuclear cells.

• Support organizations are good places to get information about medical care. Links to these organizations can be found here.
• CDC funds hepatitis C coordinators within the states to implement programs regarding hepatitis C prevention. Links and phone numbers to coordinators in your state.
• To contact Social Security for an assessment of eligibility for financial assistance programs, see www.ssa.gov. You might also want to contact Medicaid (see http://cms.hhs.gov/medicaid/default.asp) for an eligibility assessment.
• To research the possibility of free treatment through participation in clinical trials (research studies), see www.clinicaltrials.gov.
• Roche has a Hep C Action Newsletter including details about hepatitis C treatments and services see http://www.hepcfight.com/
• The Bureau of Primary Health Care (BPHC) maintains a database of clinics/hospitals that serve those without medical resources. We do not know how these clinics charge for medical care, but these clinics could be an option for those who do not have a primary doctor and do not want to go to a walk-in clinic. The website is: <http://ask.hrsa.gov/pc/>
• The National Institutes of Health chronic hepatitis C web site has extensive information about chronic hepatitis C treatment and research. The website is available at: http://digestive.niddk.nih.gov/ddiseases/pubs/hepc_ez/.

Combination therapy with pegylated interferon and ribavirin is the treatment of choice resulting in sustained response rates of 40%-80%. (up to 50% for patients infected with the most common genotype found in the U.S. [genotype 1] and up to 80% for patients infected with genotypes 2 or 3). Interferon monotherapy is generally reserved for patients in whom ribavirin is contraindicated. Ribavirin, when used alone, does not work. Combination therapy using interferon and ribavirin is now FDA approved for the use in children aged 3-17 years.

What are the side effects of interferon therapy?

Most persons have flu-like symptoms (fever, chills, headache, muscle and joint aches, fast heart rate) early in treatment, but these lessen with continued treatment. Later side effects may include tiredness, hair loss, low blood count, trouble with thinking, moodiness, and depression. Severe side effects are rare (seen in less than 2 out of 100 persons). These include thyroid disease, depression with suicidal thoughts, seizures, acute heart or kidney failure, eye and lung problems, hearing loss, and blood infection. Although rare, deaths have occurred due to liver failure or blood infection, mostly in persons with cirrhosis. An important side effect of interferon is worsening of liver disease with treatment, which can be severe and even fatal. Interferon dosage must be reduced in up to 40 out of 100 persons because of severity of side effects, and treatment must be stopped in up to 15 out of 100 persons. Pregnant women should not be treated with interferon.

What are the side effects of combination (ribavirin + interferon) treatment?

In addition to the side effects due to interferon described above, ribavirin can cause serious anemia (low red blood cell count) and can be a serious problem for persons with conditions that cause anemia, such as kidney failure. In these persons, combination therapy should be avoided or attempts should be made to correct the anemia. Anemia caused by ribavirin can be life-threatening for persons with certain types of heart or blood vessel disease. Ribavirin causes birth defects and pregnancy should be avoided during treatment. Patients and their healthcare providers should carefully review the product manufacturer information prior to treatment.

Can anything be done to reduce symptoms or side effects due to antiviral treatment?

You should report what you are feeling to your doctor. Some side effects may be reduced by giving interferon at night or lowering the dosage of the drug. In addition, flu-like symptoms can be reduced by taking acetaminophen before treatment.

Can children receive interferon therapy for chronic hepatitis C?

The Food and Drug Administration has approved the use of the combination anti-viral therapy for the treatment of hepatitis C in children 3 to 17 years old.

What can I do for Prevention?

The following guidelines will prevent infection with the hepatitis C virus, which is spread by blood:

• Avoid sharing drug needles or any other drug paraphernalia including works for injection or bills or straws
• Avoid unsanitary tattoo methods
• Avoid unsanitary body piercing methods and acupuncture
• Avoid needlestick injury
• Avoid sharing grooming utensils
• Avoid sharing personal items such as toothbrushes, razors, and nail clippers.

Proponents of harm reduction believe that strategies such as the provision of new needles and syringes, and education about safer drug injection procedures, greatly decreases the risk of hepatitis C spreading between injecting drug users.

As a summary:

• There is no vaccine to prevent hepatitis C.
• Do not shoot drugs; if you shoot drugs, stop and get into a treatment program; if you can't stop, never share needles, syringes, water, or "works", and get vaccinated against hepatitis A & B.
• Do not share personal care items that might have blood on them (razors, toothbrushes).
• If you are a health care or public safety worker, always follow routine barrier precautions and safely handle needles and other sharps; get vaccinated against hepatitis B.
• Consider the risks if you are thinking about getting a tattoo or body piercing. You might get infected if the tools have someone else's blood on them or if the artist or piercer does not follow good health practices.
• HCV can be spread by sex, but this is rare. If you are having sex with more than one steady sex partner, use latex condoms* correctly and every time to prevent the spread of sexually transmitted diseases. You should also get vaccinated against hepatitis B.
• If you are HCV positive, do not donate blood, organs, or tissue.

References

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