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GI II Exam 2 > Liver Path 2 > Flashcards

Liver Path 2 Flashcards

1
Q

Clinicopathologic Syndromes of Viral Hepatitis

A

Acute asymptomatic infection with recovery (serologic evidence only)

Acute symptomatic hepatitis with recovery

Chronic hepatitis, with or without progression to cirrhosis

Acute liver failure with massive to submassive hepatic necrosis

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2
Q

Tests for Hepatitis Viruses

A

Antibody to viral proteins (often coat proteins) take day-weeks to develop (delay)
* IgM - initial response to acute infection
* IgG - long term response
ongoing chronic infection
past infection

Viral proteins

  • rarely measurable
  • exception: Hepatitis B

Viral nucleic acid

  • Polymerase chain reaction assays available
  • most infections will be diagnosed by detection of organism nucleic acid in the future
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3
Q

alk phos is a marker of

A

cholestasis

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4
Q

Typical Case History of Acute Viral Hepatitis

A 
30 year old woman with a 1 week history of:	
increasing fatigue
nausea
loss of taste for meat, oily foods
1-2 days of darkening urine,	
yellow eyes

PE: jaundice and moderately tender liver

AST, ALT, Alk phos elevated

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5
Q

Jaundice detected clinically once the serum bilirubin level rises above

A

3 mg per dL

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6
Q

ratio of amino transferases to alk phosphatases

A

transferases up? hepatocellular

alk phosphatases? cholestasis

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7
Q

symptoms of obstructive jaundice

A

classic constellation of tea-colored urine and clay-colored stool

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8
Q

Histology Acute Hepatitis

A

Lobular disarray
– Ballooned hepatocytes and acidophilic bodies
– Individual or confluent hepatocyte dropout
– Zonal, bridging, or panlobular necrosis
– Sinusoidal inflammatory cells
– Prominent Kupffer cells

  • Mild portal inflammation
  • No fibrosis
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9
Q

Hepatitis A Virus

A

Hepatitis A virus (ssRNA) is usually * self-limited disease, incubation period of 2 to 6 wks

Does not cause chronic hepatitis or a carrier state in the * immunocompetent patient

Generally transmitted via the * oral-fecal route, person to person/contaminated water and foods

Blood-borne transmission of HAV occurs only rarely*

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10
Q

Risk factors for Hep A infection

A

mostly unknown

sexual or houshold contact
men sex w/ men
int'l travel
day care
injection drug use
food or water outbreak
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11
Q

Hep A pathobiology

A
  • Receptor for HAV (* Picornavirus) is an integral membrane glycoprotein receptor

Genome serves as a messenger RNA that encodes both structural and nonstructural *viral proteins

In the cytoplasm * RNA translation into a polyprotein that is later processed to mature viral proteins

  • Replication membrane-bound complex generates new viral genomes that are * exported out of cell into bile and to a lesser extent into blood
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12
Q

Hepatitis Viruses that ONLY Cause Acute Self-limited Disease

A

Hepatitis A
RNA virus (picornavirus)
Good vaccine available

Hepatitis E
RNA virus (Hepeviridae)
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13
Q

Hepatitis E Virus

A

Hepatitis E virus (HEV) is an * enterically transmitted, water-borne infection

Feature of HEV infection is the * high mortality rate among pregnant women, approaching 20%.

Typically acute, self-limited icteric disease *without a chronic/carrier state, much like Hepatitis A

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14
Q

Hep E lab tests

A

Laboratory Tests
IgM antibody to hepatitis E for acute disease
IgG antibody to hepatitis E for past disease or immunity

Vaccine under development

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15
Q

Histopathology of Hepatitis E Infection

A
  • Not much information on detailed histological appearances in hepatitis E.
    Focal hepatocyte necrosis including frequent acidophil bodies, swollen (or ballooned) hepatocytes, and lymphocytic parenchymal and portal infiltrates

Canalicular cholestasis and gland-like transformation of hepatocytes.

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16
Q

Hepatitis Viruses that may Cause both Acute and Chronic Disease

A

Hepatitis B

Hepatitis B + D

Hepatitis C

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17
Q

Hepatitis B Virus

A

DNA virus (Hepadnaviridae)

Replicates through RNA intermediate (like HIV)

Blood borne

Many serologic tests have been developed

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18
Q

prognosis with Hep B

A

Spontaneous recovery in patients infected at birth is less than 5%

Adult infections * spontaneously resolve in
95-99%

5-10% of infected individuals develop * chronic disease

Low prevalence areas (USA) unprotected sex and IV drug abuse are the * chief modes of spread.

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19
Q

Clinical Signs and Symptoms of Hepatitis B Infection

A 
Fatigue
Anorexia
Nausea
Jaundice/Scleral icterus
Abdominal pain
Arthralgia
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20
Q

The rate of new HBV infections in the US

A

has declined by approximately 82% since 1991, when a national strategy to eliminate HBV infection was implemented in the United States. The decline has been greatest among children born since 1991, when routine vaccination of children was first recommended

21
Q

Hepatitis B Virion =

A

Dane particle
sphere with outer envelope, icosahedral core (nucleocapsid)
double stranded HBV DNA and viral DNA polymerase

22
Q

Hep B Serological Testing:

A 
Virus components:
viral DNA
DNA polymerase (research test)
s antigen  (surface coat protein)
e antigen  (clipped portion of core protein)

Serum antibodies:
Antibody to s (surface)
Antibody to c (core)
Antibody to e

23
Q

Sequence of serologic markers for hepatitis B viral hepatitis

A

early: Total anti-HBc
later: Anti-HBs (immune and no longer contagious)

With recovery, the anti-HBc and HBs antibodies rise and stay high, while HBeAg, HBV-DNA and HBsAg go down.

with progression to chronic, the serum markers go down but HBeAg, HBV-DNA and HBsAg stay up

24
Q

Serologic Markers for Acute Self-Limited Hepatitis B Viral Infection

A

In Acute Self-limited Infection:

In patients with acute hepatitis B, there is almost always an antibody response to HBcAg and usually an antibody response to HBsAg

With the appearance of * HBsAb, the patient becomes immune to a new HBV infection

25
Serologic Markers for Chronic Hepatitis B Viral Infection
HBsAg appears in the serum in a similar time course, but does not abate, and antibody to * HBsAg fails to develop. * HBsAg in the blood is thus the hallmark of active current HBV infection, whether acute or chronic
26
Interpretation of Serological Markers for HBV Infection
* HBsAg HBV infection (acute or chronic) * HBeAg High viral load/infectivity * HBV DNA High viral load/infectivity Anti-HBs Immunity Anti-HBc IgM Acute infection Anti-HBc IgG Past or chronic infection Anti-HBe Past or low infectivity chronic infection Anti-HBc IgG and HBsAg Chronic infection Anti-HBc IgG and anti-HBs Resolved (past) infection
27
Histopathology of Hepatitis B Infection
Acute and chronic hepatitis B infection appear essentially similar to other forms of acute and chronic hepatitis Chronic HBV distinctive histological feature is the ‘ground-glass hepatocyte’ containing abundant HBsAg
28
Hepatitis Viruses that may Cause both Acute and Chronic Disease
Hepatitis B Hepatitis B + D Hepatitis C
29
Hepatitis D (delta) Virus (HDV)
Defective RNA virus that * requires coinfection with Hepatitis B virus HBV surface antigen surrounds HDV Spread of HDV follows that of HBV, primarily through parenteral exposure It can either be acquired at the same time as a primary HBV infection or later, superimposed on a pre-existent chronic hepatitis B.  HDV is rare in the USA and in other countries with a relatively low HBV incidence  Hepatitis B surface antigen constitutes the HDV coat protein
30
most severe hepatitis
Delta hepatitis is considered to be the most severe viral hepatitis. In acute forms it produces more fatalities. In chronic forms it produces more cirrhosis Most (50-70%) cases of superinfection develop a severe form of acute hepatitis and 90% of them become chronic carriers.
31
Histopathology of Hepatitis D Infection
Acute and chronic hepatitis D infections look like any other acute or chronic hepatitis. Single distinguishing feature is the sanded nucleus due to HDAg accumulating in the nucleus of infected cells (looks like HBcAg in nucleus)
32
Hepatitis C prevalence
Most common cause of chronic hepatitis world-wide, including USA In 85% of individuals, the clinical course of the * acute infection is asymptomatic and typically missed Chronic infection can lead to cirrhosis and Hepatocellular carcnoma in up to 25%
33
Hepatitis C (HCV) clinical features
Clinical feature that is quite characteristic of chronic HCV infection is persistent elevations in serum aminotransferases In symptomatic acute HCV infection, anti-HCV antibodies are initially detected in only 50% to 70% of patients In the remaining patients, the anti-HCV antibodies emerge after 3 to 6 weeks.
34
the Hep C virus itself
Small single-stranded RNA virus (described in 1989) which has an inherently * unstable genome (mutates) Rate of transmission by blood transfusion* is now close to zero Chronic disease occurs in the majority of HCV-infected individuals (80% to 90%)*
35
Risk Factors for HCV Infection
Intravenous drug abuse (54%) Multiple sex partners (36%) Having had surgery within the last 6 month (16%) Needle stick injury (10%)
36
Hepatitis C Serology
Hepatitis C IgG antibody: Appears weeks after onset of new infection Signifies past resolved or chronic hepatitis C Occasional false positive Hepatitis C RNA (by PCR): Signifies the virus is present in liver/blood Found in acute or chronic hepatitis C
37
Histopathology of Hepatitis C Infection
Acute and chronic hepatitis C infection appear essentially similar to other forms of acute and chronic hepatitis Steatosis and bile duct damage may also be found. Asymptomatic patients, even those without serum aminotransferase elevations, may have significantly abnormal histology
38
Hepatitis C Treatment
New direct-acting oral agents capable of curing hepatitis C virus (HCV) infection have been approved for use in the United States. Effective hepatitis C medications cost $1,000 a pill and more than $100,000 for a full course of treatment
39
Summary of Clinicopathologic Features of Viral Hepatitis
Acute asymptomatic: All of the hepatotropic viruses Acute symptomatic: All of the hepatotropic viruses Acute liver failure: Viral hepatitis is responsible for about 10% of cases of acute liver failure HAV, HEV and HBV, HDV
40
Chronic and carrier states
Chronic hepatitis HCV >80% HBV less than 10% in adults (perinatal >90%) Carrier state Small number of HBV No HCV
41
HIV and Chronic Viral Hepatitis
10% of HIV-infected individuals are co-infected with HBV and 25% with HCV (USA) In patients with acquired immunodeficiency syndrome (AIDS), liver disease is the second most common cause of death
42
Hepatitis C and Hepatitis A
In the presence of chronic hepatitis C * hepatitis A can become life-threatening. If there is no prior evidence of infection with hepatitis A in people with hepatitis C, Hepatitis A immunization is strongly recommended.
43
Hepatitis B and Hepatitis A
In the presence of chronic hepatitis B * hepatitis A can become life-threatening. If there is no prior evidence of infection with hepatitis A in people with hepatitis B, Hepatitis A immunization is strongly recommended.
44
vowels and consonants
The vowels (hepatitis A and E) never cause chronic hepatitis, only AcutE hepatitis, except HEV in immunocompromised hosts and pregnant females. Only the consonants (hepatitis B, C, D) have the potential to cause chronic disease (C for consonant and for chronic). Hepatitis B can be transmitted by blood, birthing, and sexual intercourse.
45
Mnemonics for C, D and E
Hepatitis C is the single virus that is more often chronic than not (almost never detected acutely; 80% or more of patients develop chronic hepatitis, 20% of whom will develop cirrhosis). Hepatitis D, the delta agent, is a defective virus, requiring hepatitis B co-infection for its own capacity to infect and replicate. Hepatitis E is endemic in equatorial regions and frequently epidemic.
46
grading, staging, and carcinoma
The inflammatory cells in both acute and chronic viral hepatitis are mainly T cells; it is the pattern of injury that is different between the two time courses, not the nature of the infiltrate. Biopsy assessment in chronic viral hepatitis is most important for grading and staging of disease, which are used to decide whether a patient undergoes often arduous antiviral treatments. Patients with long-standing HBV or HCV related cirrhosis are at increased risk for the development of hepatocellular carcinoma.
47
hypervitaminosis A
--> hepatic stellate cell lipidosis
48
virus that happens to people who travel
Hep E | common in the rest of the world (Mexico, India) even though it's not common here

GI II Exam 2 (16 decks)

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