Viral Hepatitis by hQeoR4cc

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									     HEPATITIS
       Dr. Adil Khazindar
Consultant Medicine & Infectious
            Diseases
             KAAUH
          Types of Viral Hepatitis
HepatitisA
Is an acute liver disease caused by the hepatitis A virus (HAV), lasting from a
few weeks to several months. It does not lead to chronic infection.
Transmission: Ingestion of fecal matter, even in microscopic amounts, from
close person-to-person contact or ingestion of contaminated food or drinks.
Vaccination: Hepatitis A vaccination is recommended for all children starting at
age 1 year, travelers to certain countries, and others at risk

Hepatitis B
 Is a liver disease caused by the hepatitis B virus (HBV). It ranges in severity
from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic)
illness that can lead to liver disease or liver cancer.
Transmission: Contact with infectious blood, semen, and other body fluids from
having sex with an infected person, sharing contaminated needles to inject
drugs, or from an infected mother to her newborn.
Vaccination: Hepatitis B vaccination is recommended for all infants, older
children and adolescents who were not vaccinated previously, and adults at risk
for HBV infection.

 Hepatitis C
 is a liver disease caused by the hepatitis C virus (HCV). HCV infection
sometimes results in an acute illness, but most often becomes a chronic
condition that can lead to cirrhosis of the liver and liver cancer.
Transmission: Contact with the blood of an infected person, primarily through
sharing contaminated needles to inject drugs.
 Vaccination: There is no vaccine for hepatitis C.
       Types of Viral Hepatitis
Hepatitis D
Is a serious liver disease caused by the hepatitis D virus (HDV)
and relies on HBV to replicate.
Transmission: Contact with infectious blood, similar to how HBV
is spread.
Vaccination: There is no vaccine for hepatitis D.

Hepatitis E
Is a serious liver disease caused by the hepatitis E virus (HEV)
that usually results in an acute infection. It does not lead to a
chronic infection. While rare in the United States, hepatitis E is
common in many parts of the world.
Transmission: Ingestion of fecal matter, even in microscopic
amounts; outbreaks are usually associated with contaminated
water supply in countries with poor sanitation.
Vaccination: There is currently no FDA-approved vaccine for
hepatitis E.
                        Hepatitis A
   Hepatitis A, caused by infection with the hepatitis A virus
    (HAV).
   has an incubation period of approximately 28 days (range:
    15–50 days).
   HAV replicates in the liver and is shed in high concentrations
    in feces from 2 weeks before to 1 week after the onset of
    clinical illness.
    HAV infection produces a self-limited disease that does not
    result in chronic infection or chronic liver disease.
   However, 10%–15% of patients might experience a relapse of
    symptoms during the 6 months after acute illness.
   Acute liver failure from hepatitis A is rare (overall case-fatality
    rate: 0.5%).
    The risk for symptomatic infection is directly related to age,
    with >80% of adults having symptoms compatible with acute
    viral hepatitis and the majority of children having either
    asymptomatic or unrecognized infection.
   Antibody produced in response to HAV infection persists for
    life and confers protection against reinfection.
                 Incidence
 There were 30,000 cases of Hepatitis A reported
  to the CDC in the U.S. in 1997.
 The agency estimates that there were as many as
  270,000 cases each year from 1980 through
  2000.
 there were an estimated 32,000 new hepatitis A
  virus infections in 2006. (However, the official
  number of reported hepatitis A cases is much
  lower since many people who are infected never
  have symptoms and are never reported to public
  health officials.
           How is HAV transmitted?

   Person-to-person transmission through the fecal-oral
    route (i.e., ingestion of something that has been
    contaminated with the feces of an infected person) is the
    primary means of HAV transmission in the United States. Most
    infections result from close personal contact with an infected
    household member or sex partner.
   Common-source outbreaks and sporadic cases also can occur
    from exposure to fecally contaminated food or water.
    Uncooked HAV-contaminated foods have been recognized as
    a source of outbreaks.
   Cooked foods also can transmit HAV if the temperature during
    food preparation is inadequate to kill the virus or if food is
    contaminated after cooking, as occurs in outbreaks associated
    with infected food handlers.
    Waterborne outbreaks are infrequent in developed countries
    with well-maintained sanitation and water supplies.
      Who is at increased risk for
       acquiring HAV infection?
   Travelers to countries with high or
    intermediate endemicity of HAV
    infection
   Users of injection and non-injection
    illegal drugs
   Persons with clotting factor disorders
   Persons working with nonhuman
    primates susceptible to HAV infection
              Signs & Symptoms
     Some persons, particularly young children, are asymptomatic.
    When symptoms are present, they usually occur abruptly and can
    include the following:
   Fever
   Fatigue
   Loss of appetite
   Nausea
   Vomiting
   Abdominal pain
   Dark urine
   Clay-colored bowel movements
   Joint pain
   Jaundice .
     When symptoms occur, how long do they usually last?
     Symptoms usually last less than 2 months, although 10%–15%
    of symptomatic persons have prolonged or relapsing disease for
    up to 6 months.
How long does HAV survive outside the body?
        How can the virus be killed?

   HAV can live outside the body for months,
    depending on the environmental
    conditions.
   The virus is killed by heating to 185
    degrees F (85 degrees C) for one minute.
   However, the virus can still be spread
    from cooked food if it is contaminated
    after cooking.
    Adequate chlorination of water, as
    recommended in the United States, kills
    HAV that enters the water supply.
                    Cont.
   Can hepatitis A become chronic?
    No. Hepatitis A does not become chronic.
   Can persons become reinfected with
    HAV after recovering from hepatitis
    A?
    No. IgG antibodies to HAV, which appear
    early in the course of infection, provide
    lifelong protection against the disease.
How is HAV infection prevented?
   Vaccination with the full, two-dose series of hepatitis A
    vaccine is the best way to prevent HAV infection.
   Hepatitis A vaccine has been licensed in the United States
    for use in persons 12 months of age and older.
   The vaccine is recommended for persons who are more
    likely to get HAV infection or are more likely to get
    seriously ill if they get hepatitis A
   Immune globulin is available for short-term protection
    (approximately 3 months) against hepatitis A, both pre-
    and post-exposure. Immune globulin must be administered
    within 2 weeks after exposure for maximum protection.
   Good hygiene — including handwashing or use of hand
    sanitizer after using the bathroom, changing diapers, and
    before preparing or eating food — is also integral to
    hepatitis A prevention, given that the virus is transmitted
    through the fecal–oral route.
       Who should be vaccinated
         against hepatitis A?
   All children at age 1 year (i.e., 12–23
    months). Children who have not been vaccinated by age
    2 can be vaccinated at subsequent visits.
   Children and adolescents ages 2–18 who live in
    states or communities where routine hepatitis A
    vaccination has been implemented because of high
    disease incidence.
   Persons traveling to or working in countries that
    have high or intermediate rates of hepatitis A.
   Persons traveling to or working in countries that
    have high or intermediate rates of hepatitis A.
   Persons who have occupational risk for infection
   Persons who have chronic liver disease.
   Persons who have clotting-factor disorders
               Hepatitis A Vaccine
   How long does protection from hepatitis A vaccine last?
    A recent review by an expert panel, which evaluated the projected
    duration of immunity from vaccination, concluded that protective
    levels of antibody to HAV could be present for at least 25 years in
    adults and at least 14–20 years in children.
   Can hepatitis A vaccine be administered concurrently with other
    vaccines?
    Yes. Hepatitis B, diphtheria, poliovirus (oral and inactivated), tetanus,
    oral typhoid, cholera, Japanese encephalitis, rabies, and yellow fever
    vaccines and immune globulin can be given at the same time that
    hepatitis A vaccine is given, but at a different injection site.
   Can hepatitis A vaccine be given during pregnancy?
    The safety of hepatitis A vaccination during pregnancy has not been
    determined; however, because the vaccine is produced from
    inactivated HAV, the theoretical risk to the developing fetus is
    expected to be low. The risk associated with vaccination, however,
    should be weighed against the risk for hepatitis A in women who
    might be at high risk for exposure to HAV.
   Can hepatitis A vaccine be given to immunocompromised persons
    (e.g., persons on hemodialysis or persons with AIDS)?
    Yes. Because hepatitis A vaccine is inactivated, no special
    precautions need to be taken when vaccinating immunocompromised
    persons.
                               Hepatitis B
   Hepatitis B is a disease caused by hepatitis B virus which infects the liver of
    hominoidae, including humans, and causes an inflammation called hepatitis. Originally
    known as "serum hepatitis",
   The disease has caused epidemics in parts of Asia and Africa, and it is endemic in
    China.
    About a third of the world's population, more than 2 billion people, have been
    infected with the hepatitis B virus.
   This includes 350 million chronic carriers of the virus.
    Transmission of hepatitis B virus results from exposure to infectious blood or body
    fluids containing blood.
   The acute illness causes liver inflammation, vomiting, jaundice and—rarely—death.
    Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer—a fatal
    disease with very poor response to current chemotherapy.
    The infection is preventable by vaccination.
   Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a
    DNA virus—and it has a circular genome composed of partially double-stranded DNA.
   The viruses replicate through an RNA intermediate form by reverse transcription, and
    in this respect they are similar to retroviruses.
    Although replication takes place in the liver, the virus spreads to the blood where
    virus-specific proteins and their corresponding antibodies are found in infected people.
    Bloods test for these proteins and antibodies are used to diagnose the infection.
                               History
   The earliest record of an epidemic caused by Hepatitis B virus was made
    by Lurman in 1885.
   An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard
    employees were vaccinated with lymph from other people. After several
    weeks, and up to eight months later, 191 of the vaccinated workers
    became ill with jaundice and were diagnosed as suffering from serum
    hepatitis.
    Other employees who had been inoculated with different batches of
    lymph remained healthy.
    Lurman's paper, now regarded as a classical example of an
    epidemiological study, proved that contaminated lymph was the source of
    the outbreak.
    Later, numerous similar outbreaks were reported following the
    introduction, in 1909, of hypodermic needles that were used, and more
    importantly reused, for administering Salvarsan for the treatment of
    syphilis.
   The virus was not discovered until 1965 when Baruch Blumberg, then
    working at the National Institutes of Health (NIH), discovered the Australia
    antigen (later known to be Hepatitis B surface antigen, or HBsAg) in the
    blood of Australian aboriginal people.
   Although a virus had been suspected since the research published by
    MacCallum in 1947, D.S. Dane and others discovered the virus particle in
    1970 by electron microscopy.
    By the early 1980s the genome of the virus had been sequenced, and the
    first vaccines were being tested.
                             HBV
   Hepatitis B virus (HBV) is a member of the Hepadnavirus
    family.
   The virus particle, (virion) consists of an outer lipid
    envelope and an icosahedral nucleocapsid core composed of
    protein.
   The nucleocapsid encloses the viral DNA and a DNA
    polymerase that has reverse transcriptase activity.
   The outer envelope contains embedded proteins which are
    involved in viral binding of, and entry into, susceptible cells.
   The virus is one of the smallest enveloped animal viruses
    with a virion diameter of 42nm, but pleomorphic forms
    exist, including filamentous and spherical bodies lacking a
    core.
   These particles are not infectious and are composed of the
    lipid and protein that forms part of the surface of the virion,
    which is called the surface antigen (HBsAg), and is
    produced in excess during the life cycle of the virus.
                         HBV Genome
   The genome of HBV is made of circular DNA, but it is unusual because the DNA is not
    fully double-stranded.
   One end of the full length strand is linked to the viral DNA polymerase.
   The genome is 3020-3320 nucleotides long (for the full length strand) and 1700-
    2800 nucleotides long (for the short length strand).
    The negative-sense, (non-coding), is complementary to the viral mRNA.
   The viral DNA is found in the nucleus soon after infection of the cell.
    The partially double-stranded DNA is rendered fully double-stranded by completion
    of the (+) sense strand and removal of a protein molecule from the (-) sense strand
    and a short sequence of RNA from the (+) sense strand.
   Non-coding bases are removed from the ends of the (-)sense strand and the ends
    are rejoined.
   There are four known genes encoded by the genome called C, X, P, and S. The core
    protein is coded for by gene C (HBcAg), and its start codon is preceded by an
    upstream in-frame AUG start codon from which the pre-core protein is produced.
    HBeAg is produced by proteolytic processing of the pre-core protein. The DNA
    polymerase is encoded by gene P. Gene S is the gene that codes for the surface
    antigen (HBsAg).
   The HBsAg gene is one long open reading frame but contains three in frame "start"
    (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S.
   Because of the multiple start codons, polypeptides of three different sizes called
    large, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced.
    The function of the protein coded for by gene X is not fully understood.
                          Replication
   The life cycle of Hepatitis B virus is complex.
   Hepatitis B is one of a few known non-retroviral viruses which use reverse
    transcription as a part of its replication process.
   The virus gains entry into the cell by binding to a receptor on the surface
    of the cell and enters it by endocytosis.
   Because the virus multiplies via RNA made by a host enzyme, the viral
    genomic DNA has to be transferred to the cell nucleus by host proteins
    called chaperones.
   The partially double stranded viral DNA is then made fully double stranded
    and transformed into covalently closed circular DNA (cccDNA) that serves
    as a template for transcription of four viral mRNAs.
   The largest mRNA, (which is longer than the viral genome), is used to
    make the new copies of the genome and to make the capsid core protein
    and the viral DNA polymerase.
   These four viral transcripts undergo additional processing and go on to
    form progeny virions which are released from the cell or returned to the
    nucleus and re-cycled to produce even more copies.
   The long mRNA is then transported back to the cytoplasm where the virion
    P protein synthesizes DNA via its reverse transcriptase activity.
                     Prevalence
   The primary method of transmission reflects the prevalence
    of chronic HBV infection in a given area.
   In low prevalence areas such as the continental United
    States and Western Europe, where less than 2% of the
    population is chronically infected, injection drug abuse and
    unprotected sex are the primary methods, although other
    factors may be important.
    In moderate prevalence areas, which include Eastern
    Europe, Russia, and Japan, where 2-7% of the population is
    chronically infected, the disease is predominantly spread
    among children.
   In high prevalence areas such as China and South East
    Asia, transmission during childbirth is most common,
    although in other areas of high endemicity such as Africa,
    transmission during childhood is a significant factor.
    The prevalence of chronic HBV infection in areas of high
    endemicity is at least 8%.
                   Transmission
   Transmission of hepatitis B virus results from exposure to
    infectious blood or body fluids containing blood.
   Possible forms of transmission include (but are not limited
    to) unprotected sexual contact, blood transfusions, re-use
    of contaminated needles & syringes, and vertical
    transmission from mother to child during childbirth.
   Without intervention, a mother who is positive for HBsAg
    confers a 20% risk of passing the infection to her offspring
    at the time of birth. This risk is as high as 90% if the
    mother is also positive for HBeAg.
    HBV can be transmitted between family members within
    households, possibly by contact of nonintact skin or mucous
    membrane with secretions or saliva containing HBV.
   However, at least 30% of reported hepatitis B among
    adults cannot be associated with an identifiable risk factor.
                           Symptoms
    Acute infection with hepatitis B virus
    Is associated with acute viral hepatitis – an illness that begins with
    general ill-health, loss of appetite, nausea, vomiting, body aches, mild
    fever, dark urine, and then progresses to development of jaundice.
   It has been noted that itchy skin has been an indication as a possible
    symptom of all hepatitis virus types.
   The illness lasts for a few weeks and then gradually improves in most
    affected people.
   A few patients may have more severe liver disease (fulminant hepatic
    failure), and may die as a result of it.
   The infection may be entirely asymptomatic and may go unrecognized.
    Chronic infection with Hepatitis B virus
    May be either asymptomatic or may be associated with a chronic
    inflammation of the liver (chronic hepatitis), leading to cirrhosis over a
    period of several years.
   This type of infection dramatically increases the incidence of hepatocellular
    carcinoma (liver cancer).
    Chronic carriers are encouraged to avoid consuming alcohol as it
    increases their risk for cirrhosis and liver cancer.
    Hepatitis B virus has been linked to the development of Membranous
    glomerulonephritis (MGN).
Diagnosis
                                 Treatment
   Acute hepatitis B infection does not usually require treatment because most adults clear
    the infection spontaneously.
   Early antiviral treatment may only be required in fewer than 1% of patients, whose
    infection takes a very aggressive course ("fulminant hepatitis") or who are
    immunocompromised.
   On the other hand, treatment of chronic infection may be necessary to reduce the risk of
    cirrhosis and liver cancer.
   Chronically infected individuals with persistently elevated serum alanine
    aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for
    therapy.
   Although none of the available drugs can clear the infection, they can stop the virus from
    replicating, and minimize liver damage such as cirrhosis and liver cancer.
   Currently, there are seven medications licensed for treatment of hepatitis B infection in
    the United States. These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera),
    tenofovir (Viread), telbivudine (Tyzeka) and entecavir (Baraclude) and the two immune
    system modulators interferon alpha-2a and alfa-2a (Pegasys).
   The use of interferon, which requires injections daily or thrice weekly, has been
    supplanted by long-acting pegylated interferon, which is injected only once weekly.
    However, some individuals are much more likely to respond than others and this might
    be because of the genotype of the infecting virus or the patient's heredity.
    The treatment works by reducing the viral load, (the amount of virus particles as
    measured in the blood), which in turn reduces viral replication in the liver.
   Infants born to mothers known to carry hepatitis B can be treated with antibodies to the
    hepatitis B virus (hepatitis B immune globulin or HBIg). When given with the vaccine
    within twelve hours of birth, the risk of acquiring hepatitis B is reduced 95%. This
    treatment allows a mother to safely breastfeed her child.
                     Reactivation
   Hepatitis B virus DNA persists in the body after infection
    and in some people the disease re-occurs.
   Although rare, reactivation is seen most often in people
    with impaired immunity.
   Hepatitis B goes through cycles of replication and non-
    replication.
   Approximately 50% of patients experience acute
    reactivation.
    Male patients with baseline ALT of 200 UL/L are three
    times more likely to develop a reactivation than patients
    with lower levels.
   Patients who undergo chemotherapy are at risk for HBV
    reactivation.
   The current view are that immunosuppressive drugs favor
    increased HBV replication while inhibiting cytotoxic T cell
    function in the liver.
                         Prognosis
   Hepatitis B virus infection may either be acute (self-limiting) or
    chronic (long-standing). Persons with self-limiting infection clear
    the infection spontaneously within weeks to months.
   Children are less likely than adults to clear the infection. More
    than 95% of people who become infected as adults or older
    children will stage a full recovery and develop protective immunity
    to the virus.
    However, only 5% of newborns that acquire the infection from
    their mother at birth will clear the infection.
   This population has a 40% lifetime risk of death from cirrhosis or
    hepatocellular carcinoma.
   Of those infected between the age of one to six, 70% will clear
    the infection.
   Hepatitis D infection can only occur with a concomitant infection
    with Hepatitis B virus because the Hepatitis D virus uses the
    Hepatitis B virus surface antigen to form a capsid.
    Co-infection with hepatitis D increases the risk of liver cirrhosis
    and liver cancer.
    Polyarteritis nodosa is more common in people with hepatitis B
    infection.
                           Prevention
   Several vaccines have been developed for the prevention of hepatitis B virus
    infection.
   These rely on the use of one of the viral envelope proteins (hepatitis B
    surface antigen or HBsAg).
   The vaccine was originally prepared from plasma obtained from patients who
    had long-standing hepatitis B virus infection.
    However, currently, these are more often made using recombinant DNA
    technology, though plasma-derived vaccines continue to be used; the two
    types of vaccines are equally effective and safe.
   Following vaccination Hepatitis B Surface antigen may be detected in serum
    for several days; this is known as vaccine antigenaemia.
    Vaccine is generally administered in either a two, three, or four dose
    schedules; and can be received by infants to adults.
    It provides protection for 85-90% of individuals, and lasts for 23 years.
   Unlike Hepatitis A, Hepatitis B does not generally spread through water and
    food.
    Instead, it is transmitted through body fluids, from which prevention is
    taken to avoid: unprotected sexual contact, blood transfusions, re-use of
    contaminated needles and syringes, and vertical transmission during child
    birth.
   Infants may be vaccinated at birth.
                                   HCV
   Hepatitis C is an infectious disease affecting the liver, caused by the
    hepatitis C virus (HCV).
   The infection is often asymptomatic, but once established, chronic infection
    can progress to scarring of the liver (fibrosis), and advanced scarring
    (cirrhosis).
   In some cases, those with cirrhosis will go on to develop liver failure or
    other complications of cirrhosis, including liver cancer.
   The hepatitis C virus (HCV) is spread by blood-to-blood contact.
   Most people have few symptoms after the initial infection, yet the virus
    persists in the liver in about 80% of those infected.
   Persistent infection can be treated with medication, such as interferon and
    ribavirin, but only a minority is cured.
   Those who develop cirrhosis or liver cancer may require a liver transplant,
    although the virus may recur after transplantion.
   An estimated 150-200 million people worldwide are infected with hepatitis
    C. Apart from humans, it only infects chimpanzees.
   No vaccine against hepatitis C is available. The existence of hepatitis C
    (originally "non-A non-B hepatitis") was postulated in the 1970s and proved
    conclusively in 1988.
   It is one of five known hepatitis viruses: A, B, C, D, and E.
                                       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, and his research
    team demonstrated that most post-transfusion hepatitis cases were not due to hepatitis A
    or B viruses.
   Despite this discovery, international research efforts 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,
    collaborating with Dr. D.W. Bradley from CDC, utilized a novel molecular cloning approach
    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. Chiron filed for several patents on the
    virus and its diagnosis.
   A competing patent application by the CDC was dropped in 1990 after Chiron paid $1.9
    million to the CDC and $337,500 to Bradley.
    In 1994 Bradley sued Chiron, seeking to invalidate the patent, have himself included as a
    co-inventor, and receive damages and royalty income. He dropped the suit in 1998 after
    losing before an appeals court.
   In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical
    Research for "pioneering work leading to the discovery of the virus that causes hepatitis C
    and the development of screening methods that reduced the risk of blood transfusion-
    associated hepatitis in the U.S. from 30% in 1970 to virtually zero in 2000."
   In 2004 Chiron held 100 patents in 20 countries related to hepatitis C and had successfully
    sued many companies for infringement.
    Scientists and competitors have complained that the company hinders the fight against
    hepatitis C by demanding too much money for its technology
                                Virology
   The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped, single-
    stranded, positive sense RNA virus.
   It is the only known member of the hepacivirus genus in the family
    Flaviviridae. There are six major genotypes of the hepatitis C virus, which
    are indicated numerically (e.g., genotype 1, genotype 2, etc.).
   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, rarely, 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 an STD (like HIV) is also present and makes blood contact
    more likely.
                         Epidemiology
   Hepatitis C infects nearly 200 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,
    and hepatitis C is the leading cause of liver transplant in the USA.
   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.
   Prevalence is higher in some countries in Africa and Asia.
    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.
   Regardless of how the epidemic started, a high rate of HCV transmission
    continues in Egypt, both iatrogenically and within the community and
    household.
           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.
                       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 use 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.
   Drug use by nasal inhalation (Drugs that 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.
                    Transmission Cont.
   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.
   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.[12]
                    Transmission Cont.
   Sexual transmission of HCV is considered to be rare.
    Studies show the risk of sexual transmission in heterosexual, monogamous relationships is
    extremely rare or even null.
    The CDC does not recommend the use of condoms between long-term monogamous 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
   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. Despite these
    risks, it is rare for tattoos to be directly associated with HCV infection and the U.S.
   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. Appropriate caution should be taken regarding any medical condition
    which results in bleeding such as canker sores, cold sores, and immediately after flossing.
   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 transmitting
    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 breastfeeding.
                 Signs &Symptoms
     Acute
   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 15-40% 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 60-85% 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.
                            Chronic HCV
   Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for
    more than six months.
   Clinically, it is often asymptomatic (without symptoms) 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 suggest 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.
                                   Cont.
   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, bruising and
    bleeding tendency, bone pain, varices, 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 with hyperthyreosis or hypothyreosis, porphyria cutanea
    tarda, cryoglobulinemia (a form of small-vessel vasculitis) and
    glomerulonephritis, specifically membranoproliferative glomerulonephritis
    (MPGN).
    Hepatitis C is also associated with sicca syndrome (an autoimmune
    disorder), thrombocytopenia, lichen planus, diabetes mellitus and with B-cell
    lymphoproliferative disorders.
                                 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. Rarely, people infected with HCV never develop
    antibodies to the virus and therefore, never test positive using HCV antibody
    screening.
   Because of this possibility, RNA testing (see nucleic acid testing methods below)
    should be considered when antibody testing is negative but suspicion of hepatitis
    C is high (e.g. because of elevated transaminases in someone with risk factors
    for hepatitis C).
                   Diagnosis cont.
   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. HCV genotype testing is used to
    determine the required length and potential response to
    interferon-based therapy
                                  Treatment
   There is a very small chance of clearing the virus spontaneously in chronic HCV carriers
    (0.5 to 0.74% per year), however, 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 response still have actively replicating virus in their liver and
    peripheral blood mononuclear cells.
   The evidence for treatment in genotype 6 disease is currently sparse, and the evidence
    that exists is for 48 weeks of treatment at the same doses as are used for genotype 1
    disease.
   Physicians considering shorter durations of treatment (e.g., 24 weeks) should do so within
    the context of a clinical trial.
   Treatment during the acute infection phase has much higher success rates (greater than
    90%) with a shorter duration of treatment; however, this must be balanced against the
    15-40% chance of spontaneous clearance without treatment
                    Treatment Cont.
   Those with low initial viral loads respond much better to treatment
    than those with higher viral loads (greater than 2 million virions/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 for 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.
   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.
           During Pregnancy & Breast
                    Feeding
   If a pregnant woman has risk factors for hepatitis C, she should be tested for
    antibodies against HCV.
   About 4% infants born to HCV infected women become infected.
   There is no treatment that can prevent this from happening.
   There is a high chance of the baby ridding the HCV in the first 12 months.
   In a mother that also has HIV, the rate of transmission can be as high as 19%.
   There are 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 Therapy
   Several alternative therapies purport to
    maintain liver functionality, rather than
    treat the virus itself, thereby slowing the
    course of the disease to retain quality of
    life.
   As an example, extract of Silybum
    marianum and Sho-saiko-to are sold for
    their HCV related effects; the first is said
    to provide some generic help to hepatic
    functions, and the second claims to aid in
    liver health and provide some antiviral
    effects.[25]
                 Experimental Therapy
   The drug viramidine, which is a prodrug of ribavirin that 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
    interferons, 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 some of these is still in
    the early phase. VX 950, also known as Telaprevir is currently in Phase 3 Trials.
    One protease inhibitor, , 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, , and DAPY.[citation needed] Antisense phosphorothioate oligos have been
    targeted to hepatitis C.
   Antisense Morpholino oligos have shown promise in preclinical studies however, they were
    found to cause a limited viral load reduction.
   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.
   In addition to the standard treatment with interferon and ribavirin, some studies have
    shown higher success rates when the antiviral drug amantadine (Symmetrel) is added to
    the regimen. Sometimes called "triple therapy", it involves the addition of 100 mg 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.
                        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
   Avoid unsanitary acupuncture
   Avoid needlestick injury
   Avoid sharing personal items such as toothbrushes, razors, and
    nail clippers.
   Use latex condoms correctly and every time you have sex if not in
    a long-term monogamous relationship
   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.
   No vaccine protects against contracting hepatitis C, or helps to
    treat it. Vaccines are under development and some have shown
    encouraging results.
          Autoimmune Hepatitis
   Autoimmune hepatitis is a disease in which the
    body’s own immune system attacks the liver and
    causes it to become inflamed.
   The disease is chronic, meaning it lasts many
    years.
   If untreated, it can lead to cirrhosis and liver
    failure.
   There are two forms of this disease.
    Type 1, or classic, autoimmune hepatitis is the
    more common form. This is the form that mostly
    affects young women and is often associated with
    other autoimmune diseases.
    Type 2 autoimmune hepatitis is less common
    and generally affects girls between the ages of 2
    and 14.
           What Is The Cause?
   The immune system normally attacks bacteria,
    viruses and other invading organisms.
   It is not supposed to attack your own cells; if it
    does, the response is called autoimmunity.
    In autoimmune hepatitis, the immune system
    attacks your liver cells, causing long-term
    inflammation and liver damage.
   Scientists don’t know why the body attacks itself
    in this way, although heredity and prior infections
    may play a role.
             Who Is at Risk?
   About 70 percent of people with
    autoimmune hepatitis are women,
    usually between the ages of 15 and
    40.
   Many people with this disease also
    have other autoimmune diseases,
    including type 1 diabetes, thyroiditis,
    ulcerative colitis, vitiligo, or Sjogren’s
    syndrome .
                  Symptoms
   Often, the symptoms of autoimmune hepatitis
    are minor.
   When symptoms do occur, the most common are
    fatigue, abdominal discomfort, aching joints,
    itching, jaundice, enlarged liver, nausea and
    spider angiomas (blood vessels) on the skin.
   Other symptoms may include dark urine, loss of
    appetite, pale stools and absence of
    menstruation.
    More severe complications can include ascites
    and mental confusion.
                         Diagnosis
   Blood tests. A routine blood test for liver enzymes can help
    reveal a pattern typical of hepatitis, but further tests, especially
    for autoantibodies, are needed to diagnose autoimmune hepatitis.
   Antibodies are proteins made by the immune system to fight off
    bacteria and viruses. Autoantibodies attack the body’s cells.
   In autoimmune hepatitis, the immune system makes one or more
    types of autoantibodies.
   The most common are antinuclear antibodies (ANA), smooth
    muscle antibodies (SMA), and antibodies to liver and kidney
    microsomes (anti-LKM). People with type 1 have ANA, SMA, or
    both, and people with type 2 have anti-LKM.
   Blood tests also help distinguish autoimmune hepatitis from other
    diseases that resemble it, such as viral hepatitis B or C or a
    metabolic disease such as Wilson disease.
   Liver biopsy. A tiny sample of liver tissue, examined with a
    microscope, can help doctors accurately diagnose autoimmune
    hepatitis and tell how serious it is.
                                 Treatment
   The primary treatment is medicine to suppress, or slow down, an overactive immune
    system.
   Both types of autoimmune hepatitis are treated with daily doses of a corticosteroid called
    prednisone.
   Treatment may begin with a high dose of 30 to 60 mg per day and be lowered to 10 to
    20 mg per day as the disease is controlled. The goal is to find the lowest possible dose
    that will control the disease.
   Another medicine, azathioprine (Imuran) is also used to treat autoimmune hepatitis. Like
    prednisone, azathioprine suppresses the immune system, but in a different way.
   Treatment may begin with both azathioprine and prednisone, or azathioprine may be
    added later, once the disease is under control. The use of azathioprine allows for a lower
    dose of prednisone, which in turn reduces predisone’s side effects.
   In about seven out of 10 people, the disease goes into remission within 3 years of
    starting treatment. Remission occurs when symptoms disappear and lab tests show
    improvement in liver function.
   Some people can eventually stop treatment, although many will see the disease return.
    People who stop treatment must carefully monitor their condition and promptly report
    any new symptoms to their doctor.
    Treatment with low doses of prednisone or azathioprine may be necessary on and off for
    years, if not for life.
   Some people with mild forms of the disease may not need to take medication. Doctors
    assess each patient individually to determine whether those with mild autoimmune
    hepatitis should undergo treatment.
             Other Treatment
   People who do not respond to standard
    immune therapy or who have severe side
    effects may benefit from other
    immunosuppressive agents such as
    mycophenylate mofetil, cyclosporine, or
    tacrolimus.
   People who progress to end-stage liver
    disease—also called liver failure—or
    cirrhosis may need a liver transplant.
   Transplantation has a 1-year survival rate
    of 90 percent and a 5-year survival rate of
    70 to 80 percent.

								
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