ALSO SEE HEPATITIS B SERODIAGNOSIS ESSENTIALS

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Hepatitis and HBV Tutorial
Hepatitis
Hepatitis is inflammation of the liver, and although it could have various causes such as abuse
of alcohol and certain drugs, its most common cause is one of the five types of hepatitis viruses,
denoted by the first five letters of the alphabet, A through E. Hepatitis A is usually spread by
poor hygiene (fecal-oral route and contaminated water) as well as by sexual contact. Usually,
there are no symptoms; the patient recovers and does not become a carrier. Hepatitis B, a more
serious condition than hepatitis A, is usually transmitted by body fluids and, in case of drug
addicts, by the sharing of needles. Patients can become carriers of the virus, and in 10% of the
patients, the condition may become chronic, leading to cirrhosis and cancer of the liver. In the
past, hepatitis C was transmitted by blood transfusions, but screening has almost completely
eradicated that route and now it is transmitted mostly by shared needles among drug addicts.
About three-quarters of people who have the hepatitis C virus will reach the chronic stage, and
of these, 20% to 25% will develop cirrhosis and then liver cancer. Hepatitis D is also transmitted
by the sharing of needles and is always accompanied by hepatitis B. The double infection is a
more severe condition. Hepatitis E is spread by the fecal-oral route and is responsible for
epidemics but mostly in underdeveloped countries. Neither chronic nor carrier states are
present with this form of the hepatitis virus. Universal vaccination is recommended to protect the
population from hepatitis B, and this has the added benefit t of protection against hepatitis D; it
is recommended that travelers to underdeveloped countries where hepatitis A is prevalent be
vaccinated against hepatitis A. There are no vaccines currently available against hepatitis C or
E.
Serologic testing in HBV| See HBV Antibody-Viral Test
Surface antigen: The outer coating of the virus is made up of the surface antigen or
HBsAg. It surrounds the core of the virus.
Core antigen: The inner shell contains the core antigen (HBcAg).
E antigen: Another antigen found in the core’s interior is the “e” antigen (HBeAg).
Also, within the core of the virus are the viral DNA genetic material and the DNA
polymerase enzyme, which contains the key genetic replication instructions.

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FIRST AID 2013 (pgs. 162-65)

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VIRAL HEPATITIS: The Big Picture| Pathology
In the acute phase of HBV infection, HBV surface antigen (HBsAg) and antibodies to
HBV core antigen (anti-HBc) are detected in the serum. HBsAg disappears within 3–5
months, and antibodies to HBV surface antigen(HbsAb) do not appear until 6 months
after infection. During this variable length “window period,” anti-HBc antibody is the only
serologic marker of infection. Immunity to HBV is conferred by anti-HBV surface
antibodies (HBsAb) and is seen in resolved acute infection (Table 15-4).
Outcomes of viral hepatitis
■ Carrier state: Patients have no symptoms but can transmit
the disease; a carrier state is not seen with HAV. HBe antigen
is associated with a highly infectious state.
■ Asymptomatic infection: No symptoms.
Important clinical points
■ Hepatitis A (HAV) and hepatitis E (HEV): Have no chronic carrier state so there is no
risk of cirrhosis; rarely can HAV cause fulminant hepatic failure. When HEV causes
fulminant hepatic failure, it is most commonly associated with Southeast Asian pregnant
females.
■ Of the forms of viral hepatitis, acute hepatitis B (HBV) is most likely to cause fulminant
hepatic failure, especially if the patient is co-infected with hepatitis D (HDV).
■ Immune response is critical in the pathogenesis of acute hepatitis. A vigorous immune
response on exposure to HBV increases the risk of acute hepatitis and fulminant
hepatic failure but decreases the risk of subsequent development of the chronic carrier
state.

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■ The immune response to chronic viral hepatitis (e.g., TGF- ) is responsible for most of
the damage to the liver.
■ HAV is transmitted by the fecal-oral route. HBV is transmitted by exposure to blood or
body fluid, sexual contact, or congenital transmission. Transmission of hepatitis C
(HCV) requires exposure to blood, and conclusive evidence of routine sexual or
congenital transmission is lacking.
Formative Exam (From First Aid Q & A for the USMLE Step 1)
Micro2. A hepatitis panel is ordered for a 27-year-old woman as part of a routine work-
up for abdominal pain. Results of serologic testing are negative for HBeAg and HBsAg,
but positive for HBsAb and IgG HBcAb. Which of the following is the appropriate
conclusion?
(A) The patient has been exposed to hepatitis B and has completely recovered
(B) The patient has been exposed to hepatitis B and is in the acute disease phase
(C) The patient has been exposed to hepatitis B and is in the window phase
(D) The patient has been exposed to hepatitis B and is now chronically infected
(E) The patient has been exposed to hepatitis B but was never infected
Micro10. Oncogenic viruses act through a variety of mechanisms. Some introduce
oncogenes directly into host cells, while others force cells to repeatedly undergo cycles
of proliferation that eventually become unregulated. Still others introduce oncogenic
potential by manipulating chromosomal structure through deletions or translocations.
Which of the following viruses causes neoplasia by inactivating tumor suppressor genes
such as p53 and Rb?
(A) Epstein-Barr virus
(B) Hepatitis C virus
(C) HIV
(D) Human papillomavirus
(E) Human T-cell lymphotropic virus type 1

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Micro27. A 31-year-old pregnant woman comes to the physician because of painful
vesicular lesions that have recently appeared on her genitalia. A positive result on which
of the following diagnostic tests would mean that her baby is at risk for congenital
anomalies?
(A) Anti-hepatitis B surface antibody test
(B) Giemsa stain for cytoplasmic inclusions
(C) Monospot test
(D) Tzanck smear for multinucleated giant cells
(E) Weil-Felix test
Micro32. A 54-year-old man presents to the clinic with scleral icterus,
hepatosplenomegaly, ascites, and a history of episodes of jaundice over the past 3
years. He was involved in an auto accident when he was 21 years old, for which he
required surgery and blood transfusions. Laboratory tests show:
Aspartate aminotransferase: 734 U/L
Alanine aminotransferase: 846 U/L
Direct bilirubin: 0.1 mg/dL
Indirect bilirubin: 7.6 mg/dL
Assuming a viral etiology, which of the following is the most likely cause of this patient’s
illness?
(A) Hepatitis A
(B) Hepatitis C
(C) Hepatitis D
(D) Hepatitis E
(E) Hepatitis G

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1.GI A 35-year-old woman who is HIV-positive presents to the physician with jaundice
and right upper quadrant abdominal pain. The patient reports having had multiple
episodes of jaundice over the past 10 years. A hepatitis panel is positive for HBsAg and
anti-HBc IgM, but negative for HBsAb and anti-HAV IgM. Which of the following would
most likely be lower thannormal in this patient?
(A) Albumin
(B) Alkaline phosphatase
(C) Bilirubin
(D) Prothrombin time
(E) Transaminases
12GI. Which of the following types of hepatocellular injury is commonly seen after
acetaminophen overdose?
(A) Acute hepatitis
(B) Centrilobular necrosis
(C) Fibrosis
(D) Granuloma formation
(E) Microvesicular fatty change

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20.GI A 37-year-old woman is found by police in a confused state and is brought to the
emergency department for evaluation. The patient is unable to answer any of the
physician’s questions. Physical examination reveals jaundice. Despite aggressive
therapy the patient dies. An autopsy is performed and a microscopic view of the
patient’s liver is shown in the image.
Which of the following conditions is most consistent with these fi ndings?
(A) α1-Antitrypsin defi ciency
(B) Acute viral hepatitis
(C) Alcoholic hepatitis
(D) Fatty liver of pregnancy
(E) Neonatal hepatitis

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47FLE. A major problem in hospitals is the risk of needle sticks and the accidental
transmission of hepatitis C, hepatitis B, and HIV to health care personnel. Although
different circumstances can make the likelihood of infection higher or lower, it is well
known that the chance of infection transmission from a needle is not the same for each
of these diseases. From greatest chance of infection to least, which of the following is
the order of infection among these three diseases?
(A) Hepatitis B, hepatitis C, HIV
(B) Hepatitis C, hepatitis B, HIV
(C) Hepatitis B, HIV, hepatitis C
(D) Hepatitis C, HIV, hepatitis B
(E) HIV, hepatitis B, hepatitis C
Further Study:
HBV Antibody-Viral Test
HBV Wikipedia
A Clinical Trial
Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis with Telbivudine or
Adefovir: A Randomized Trial
http://annals.org/article.aspx?articleid=737735
Editors' Notes
Context
 Optimal regimens for suppressing virus in chronic hepatitis B infection are
unclear.
Contribution
 In this 52-week open label trial, 135 adults with hepatitis B e antigen–positive
chronic hepatitis B were randomly assigned to telbuvidine, adefovir, or adefovir
for 24 weeks followed by telbivudine for 28 weeks. The telbivudine and the
adefovir-to-telbivudine groups experienced similar reductions in viral levels that
were greater than those in the adefovir group.

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Caution
 The small trial did not establish long-term drug resistance or effects on clinical
outcomes.
Implication
 Telbivudine and switching from adefovir to telbivudine suppressed viral levels
more than adefovir in adults with chronic hepatitis B.
—The Editors
In chronic hepatitis B virus (HBV) carriers, elevated serum HBV DNA levels have been
associated with increased risk for end-stage complications, such as cirrhosis and
hepatocellular carcinoma (1–4). Corresponding evidence supports the concept that
antiviral therapy can ameliorate liver injury and reduce or delay the progression of
cirrhosis and the incidence of hepatocellular carcinoma (5–9). Effectively maintained
viral suppression has been correlated with these effects (5, 10). Recent studies further
suggest that, with direct-acting anti-HBV nucleosides and nucleotides, therapeutic
efficacy and the emergence of resistance are related to the degree of viral suppression
achieved early in the course of treatment (11–18). Specifically, achieving low serum
HBV DNA levels in the first 6 to 12 months—preferably levels undetectable by
polymerase chain reaction (PCR) assay—has been associated with greater subsequent
efficacy and less resistance, with observations now extending to treatment periods
beyond 2 years. Maximizing early viral suppression is therefore emerging as an
important therapeutic goal for patients with hepatitis B.
Telbivudine and adefovir are approved for use in the United States and elsewhere (8,
19–22). Telbivudine, a thymidine nucleoside analogue, had greater antiviral efficacy
than lamivudine in phase IIb and III trials (22–23). Adefovir, an adenosine nucleotide
analogue, had greater efficacy than placebo in phase III trials (8, 21). Telbivudine and
adefovir have not been compared directly, although HBV DNA reductions after 1 year of
telbivudine in phase III trials seemed greater than those reported with adefovir in similar
patient populations (8, 21–22).
We compared the degree of telbivudine- and adefovir-induced viral suppression after 24
and 52 weeks of treatment to assess the relative antiviral efficacy and safety of these
agents. Because trial data (8, 22) suggest that the clinical antiviral effects of telbivudine
may be greater than those of adefovir, we also assessed antiviral efficacy and safety in
patients switched to telbivudine after receiving adefovir treatment for 24 weeks. Finally,
we evaluated potential relationships between the degree of viral suppression achieved
after 6 months of therapy and subsequent efficacy outcomes at 1 year.