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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
ENTEROVIRUS INFECTION
Hand, foot, and mouth disease (aphthous-like ulcerations
on labial mucosa ) resembles herpangina (same virus),
Viral Infections: Viral Infections Requiring Ancillary Tests
but are more numerous on the buccal and labial mucosa.
(From DP: Head & Neck.)
TERMINOLOGY
Synonyms
Hand, foot, and mouth disease (Coxsackie virus A,
EV71, and others)
Herpangina (Coxsackie virus A)
Common cold (Rhinovirus)
Definitions
"pico" + "rna" + "virus" (small RNA virus)
Greek: "Enteron" (intestine)
Enteric cytopathogenic human orphan (ECHO)
Coxsackie, NY: Location of first identification of virus
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Infected persons may transmit via feces, secretions, or
blister fluid
Nondisinfected surfaces may transmit virus through
touching with contact of mucous membranes
Infectious Agents
Enterovirus
Enterovirus A-J (E-J are solely veterinary pathogens)
Coxsackievirus A and B: 29 serotypes of
enterovirus A, B, and C causing human disease
Echovirus: 28 serotypes of enterovirus B causing
human disease
Poliovirus: 3 serotypes of enterovirus C
Rhinovirus A-C
Large group of serotypes causing common cold
Parechovirus 1-15 (several formerly echovirus)
Rare, severe illness with meningitis in infants
Enterovirus D68 (EV-D68)
Like all enteroviruses, more frequent in summer
I
and fall
A hand, foot, and mouth lesion from the skin
demonstrates inflammation, dyskeratosis , and
apoptosis . (Courtesy J. Hanna, PhD, MD, and A. Laga,
MD, MMSC.)
Presents with mild to complicated severe
respiratory infection (children with asthma)
similar to influenza
Transmission is similar to influenza with
respiratory droplet spread
Appears to be rising in incidence over other
enteroviruses
CLINICAL ISSUES
Epidemiology
10-15 million infections per year (United States) with
~ 1% hospitalization rate
Mostly asymptomatic infection to common cold
Presentation
Common cold
Hand, foot, and mouth disease
Herpangina
Acute hemorrhagic conjunctivitis
Aseptic meningitis, encephalitis
Myocarditis, pericarditis
Severe neonatal "sepsis"
Acute flaccid paralysis
Laboratory Tests
ECG with ST-segment elevation to heart block
(myocarditis)
Aseptic meningitis on CSF studies
Treatment
Treatment is supportive
Prevention through washing hands, disinfecting
surfaces, avoiding sick contacts
Prognosis
Most patients are asymptomatic or fully recover with
rare instances of mortality or long-term morbidity
especially in encephalitis and paralysis cases
2
6
ENTEROVIRUS INFECTION
Clinical Issues
10-15 million infections per year (United States) with
~ 1% hospitalization rate
Aseptic meningitis, encephalitis, acute flaccid
paralysis
Myocarditis, pericarditis: ECG with ST-segment
elevation to heart block
Key Facts
Microscopic Pathology
Hand, foot, and mouth may show apoptosis of
keratinocytes, edema, necrosis, and dyskeratosis
Nonspecific lymphocytic inflammation of affected
organs (necrosis may be prominent)
Ancillary Tests
IHC: Antibodies to enterovirus capsid protein (VP1)
PCR: Performed on CSF, respiratory secretions, and
body fluids to detect enterovirus RNA
Viral Infections: Viral Infections Requiring Ancillary Tests
MICROBIOLOGY
Picornavirus
Nonenveloped, positive-stranded RNA virus with
icosahedral capsid
Culture on cynomolgus or rhesus monkey kidney cells
(< 5 days)
Genomes range from 7.2-8.5 kb
MICROSCOPIC PATHOLOGY
Histologic Features
Necrosis/hemorrhage may be prominent with no viral
cytopathic effect
Nonspecific lymphocytic inflammation of affected
organs
Myocarditis with myocyte destruction
Encephalitis with destruction of neurons
Skin in hand, foot, and mouth may show apoptosis of
keratinocytes, edema, necrosis, and dyskeratosis
ANCILLARY TESTS
Immunohistochemistry
Antibodies to Enterovirus capsid protein (VP1)
PCR
Performed on CSF, respiratory secretions, and body
fluids to detect enterovirus RNA
DIFFERENTIAL DIAGNOSIS
Other Viral Infections
Differentiation from other viral infections requires
culture, PCR, or immunohistochemistry
DIAGNOSTIC CHECKLIST
Clinically Relevant Pathologic Features
90% of infections are asymptomatic with severe
disease primarily presenting as encephalitis or
paralysis
Children < 18 years of age with neurologic or cardiac
complaints should be evaluated with high scrutiny
Pathologic Interpretation Pearls
Lymphocytic inflammatory infiltrates without viral
cytopathic effect with necrosis
Skin lesions with apoptosis of keratinocytes, edema,
necrosis, and dyskeratosis
SELECTED REFERENCES
1. Muehlenbachs A et al: Tissue tropism, pathology
and pathogenesis of enterovirus infection. J Pathol.
235(2):217-28, 2015
2. Pankuweit S et al: Viral myocarditis: from experimental
models to molecular diagnosis in patients. Heart Fail Rev.
18(6):683-702, 2013
3. Rhoades RE et al: Enterovirus infections of the central
nervous system. Virology. 411(2):288-305, 2011
GROSS AND MICROSCOPIC FEATURES
(Left) Herpangina, seen as large aphthous-like ulcerations of the soft palate, start as small vesicles that rapidly ulcerate, lasting < 10 days.
(From DP: Head & Neck.) (Center) Myocarditis in enterovirus infection shows nonspecific lymphocytic inflammation with myocyte damage
and destruction (must be confirmed by IHC, serology, PCR, or culture). (Courtesy R. Padera, PhD, MD.) (Right) Enterovirus encephalitis shows
perivascular inflammation with neuronal damage.
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HEPATITIS A AND E VIRUS INFECTIONS
Liver biopsy from acute hepatitis A virus (HAV) infection
shows extreme hepatocellular disarray, with features of
Viral Infections: Viral Infections Requiring Ancillary Tests
a lobular hepatitis as well as a cholestatic hepatitis.
(Courtesy M. Pittman, MD.)
TERMINOLOGY
Abbreviations
Hepatitis A virus (HAV)
Hepatitis E virus (HEV)
Definitions
HAV member of Picornaviridae family: Derived from
"pico" (small) and "RNA"
HEV member of Hepeviridae family: Derived from
"Hepatitis E"
ETIOLOGY/PATHOGENESIS
Infectious Agents
Viral infections transmitted by fecal-oral route,
vertically, parenterally, or through consumption of
raw or undercooked meat of infected animals
HEV animal reservoirs include pigs, deer, and rodents
Virus enters bloodstream following ingestion, then
infects and multiplies in liver hepatocytes and Kupffer
cells, and is secreted in bile and shed in stool
Symptoms due to immunopathologic response to
infected hepatocytes
Incubation period: 3-6 weeks
Infectious period: From 2 weeks before to 1 week after
onset of clinical illness
CLINICAL ISSUES
Epidemiology
Account for majority of enterically transmitted viral
hepatitis
HAV
Worldwide
1.4 million infections and 102,000 deaths
USA
annually
I
2
Liver biopsy from acute hepatitis E virus (HEV) infection
shows an acidophil body , lobular inflammation, and
activated sinusoidal Kupffer cells, features of "classic"
acute viral hepatitis. (Courtesy J. Verheij, MD, PhD.)
Declined 95% following HAV vaccine (1995);
1,562 cases reported in 2012 (3,050 estimated
cases)
1/2 of acute viral hepatitis cases in USA
HEV
Worldwide
20 million infections and 57,000 deaths annually
Endemic in parts of Asia, Africa, and India
USA
Uncommon; typically result of travel to endemic
areas
Site
Liver
Presentation
Fever
Malaise
Abdominal pain
Jaundice
Fatigue
Anorexia
Right upper quadrant pain
Hepatomegaly
Likelihood of symptomatic infection increases with
age; young children often asymptomatic
Laboratory Tests
Aminotransferases (AST & ALT): 5-10x normal values
Serology
Presence of anti-HAV IgM in patient with hepatitis
or elevated AST/ALT is diagnostic of acute HAV
infection
Anti-HAV IgG persists for life and confers protection
Presence of anti-HEV IgM diagnostic of acute HEV
infection; often diagnosis of exclusion
PCR (blood, stool)
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HEPATITIS A AND E VIRUS INFECTIONS
Etiology
Viral infections transmitted predominantly by fecaloral route
Clinical Issues
Incidence
HAV: ~ 3,000 cases/year in USA in post-vaccine era
(since 1995); 1.4 million cases/year worldwide
HEV: Incidence in USA unclear; 20 million cases/
year worldwide
Presentation: Fever, malaise, abdominal pain,
jaundice, fatigue, anorexia, right upper quadrant
pain, hepatomegaly
Laboratory tests: ALT/AST
Serology: Positive anti-HAV IgM or anti-HEV IgM
Treatment: Primarily supportive care, liver transplant
for acute liver failure, HAV vaccine for prevention
Key Facts
Natural history/prognosis: Self-limited (~ 2 months),
rare acute liver failure, no progression to chronic
hepatitis
Microscopic Pathology
Diffuse lobular predominantly lymphocytic
inflammation, hepatocyte swelling, necrosis, and
regeneration, Kupffer cell hyperplasia
Mild portal or periportal inflammation, confluent
hepatocyte necrosis (severe cases), and canalicular
cholestasis may be present
Diagnostic Checklist
Viral hepatitis laboratory tests; travel, immunization,
and medication history
Biopsy rarely undertaken except in acute liver failure
to evaluate need for transplant
Viral Infections: Viral Infections Requiring Ancillary Tests
Natural History
Generally self-limited infections (~ 2 months HAV; 1-4
weeks HEV)
Chronic HEV infection in immunosuppressed
No progression to chronic hepatitis with HAV
infection
Acute liver failure in 1% of HAV and 0.1-4.0% of HEV
infections
Treatment
Primary prevention
HAV vaccine (HAVRIX and VAQTA): 2 doses (6
months apart)
Recommended for international travelers, men
who have sex with men, all illegal drug users,
children (> 1 year old), and individuals with
chronic liver disease
No HEV vaccine licensed in USA
Postexposure prophylaxis
HAV vaccine or immune globulin (within 2 weeks)
Presentation with symptoms
Supportive therapy
Liver transplant for acute liver failure
Prognosis
0.1-2% overall mortality with HAV infection
Increased in patients with chronic liver disease and
> 40 years old
1-4% overall mortality with HEV infection
Increased mortality in pregnant women (20%)
IMAGE FINDINGS
Ultrasonographic Findings
Hepatosplenomegaly and edema; decreased liver
echogenicity
Increased echogenicity of portal venous walls ("starry
sky" appearance)
Periportal hypoechoic area (hydropic swelling of
hepatocytes)
Thickening of gallbladder wall
MR Findings
Increase in T1 and T2 relaxation times in liver
Periportal hyperintensity (fluid, lymphedema)
CT Findings
Hepatomegaly; gallbladder wall thickening
Periportal hypodensity (fluid, lymphedema)
Heterogeneous parenchymal enhancement
MICROBIOLOGY
Virus Features
HAV
Nonenveloped, single-strand RNA virus
27 nm spherical, icosahedral capsid
7,474 nucleotide genome; 1 ORF (11 proteins)
4 genotypes (I-III, VII); 1 serotype
HEV
Nonenveloped, single-strand RNA virus
32-34 nm spherical, icosahedral capsid
7,300 nucleotide genome; 3 ORFs (9 proteins)
4 genotypes (1-4); 1 serotype
Culture
No routine role for culture in diagnosis
MACROSCOPIC FEATURES
Liver
Homogeneously enlarged and congested
Cut surface is reddish brown (bright yellow or green
with cholestasis)
Shrinks and softens due to extensive necrosis in
fulminant hepatitis
MICROSCOPIC PATHOLOGY
Histologic Features
Liver
Acute lobular hepatitis
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HEPATITIS A AND E VIRUS INFECTIONS
Diffuse, mixed (predominantly lymphocytic)
inflammatory cell infiltrate
Spotty (lytic) necrosis: Small foci of lymphocytes
and macrophages surrounding individual
damaged hepatocytes or fragments of dead
hepatocytes
Numerous apoptotic bodies (acidophilic bodies)
Hepatocyte swelling
Hepatocyte regeneration
Kupffer cell hyperplasia
Mild portal and periportal inflammation may be
present
Areas of confluent hepatocyte necrosis (severe cases)
Canalicular cholestasis present in some cases
Cytologic Features
Hepatocyte swelling: Pale staining due to edema
Viral Infections: Viral Infections Requiring Ancillary Tests
ANCILLARY TESTS
Histochemical Stains
Trichome and reticulin stains show foci of
parenchymal collapse
Periodic acid-Schiff stain shows pigment-laden
macrophages
Areas of necrosis infiltrated by mononuclear cells
creating granulomatous appearance
Detection of EBV by in situ hybridization for EBVencoded RNA (EBER) or by PCR
Cytomegalovirus
Accounts for 8% of cases of infectious
mononucleosis-like syndrome with hepatic
involvement
Similar histologic findings as EBV hepatitis
Amphophilic nuclear inclusions surrounded by halo
Autoimmune Hepatitis
Positive autoimmune serologies (anti-nuclear
antibodies, anti-smooth muscle antibodies, anti-liverkidney-microsomal antibodies)
Portal and periportal hepatitis in addition to lobular
hepatitis
Prominent plasma cell infiltrates and fibrosis
Responsive to immunosuppressive therapy
Drug-/Toxin-Induced Hepatitis
Caused by toxic exposure to certain medications,
vitamins, herbal remedies, or food supplements
Histologically similar to acute viral hepatitis
Eosinophils may be prominent
Self-limited and typically resolves with cessation of
drug
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2
DIFFERENTIAL DIAGNOSIS
Other Viral Hepatidities
Hepatitis B virus
Acute hepatitis with predominant lobular injury
seen in acute infection, during disease flares, and
with hepatitis D virus superinfection
Most biopsies exhibit chronic hepatitis with
predominantly portal inflammation and fibrosis
Cytoplasmic ground-glass hepatocyte inclusions
Positive hepatitis B surface antigen (HBsAg), markers
of virus replication (HBeAg, HBV DNA), &/or antihepatitis B core antigen IgM (anti-HBcAg)
Hepatitis C virus
Acute infection rarely biopsied
Chronic hepatitis with predominantly portal
inflammation and fibrosis; hepatocellular steatosis
Positive HCV RNA (serum)
Hepatitis D virus
Only occurs in setting of acute or chronic HBV
infection
More severe necroinflammatory activity and more
rapid disease progression
Sanded hepatocyte nuclei
Positive anti-hepatitis D virus IgM (anti-HDV)
Epstein-Barr virus (EBV)
Liver involvement in > 90% of cases of infectious
mononucleosis
Portal and periportal lymphocytic infiltrate, with
occasional larger immunoblastic cells
Minimal liver cell ballooning; hepatocyte
regeneration, canalicular cholestasis, and Kupffer
cell hyperplasia
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Viral hepatitis laboratory tests
HAV: Anti-HAV IgM
HBV: HBsAg, HBeAg, HBV DNA, anti-HBcAg IgM,
anti-HBsAg
HCV: HCV RNA
HDV: Anti-HDV IgM
HEV: Anti-HEV IgM
Aminotransferase (ALT/AST) levels
History of medications and recreational drug use
Travel history to endemic areas
Immunization history (HAV and HBV)
SELECTED REFERENCES
1. Centers for Disease Control and Prevention: Hepatitis.
http://www.cdc.gov/hepatitis/. Published November 18,
2009. Updated September 18, 2014. Accessed November
2014
2. Kamar N et al: Hepatitis E virus infection. Clin Microbiol
Rev. 27(1):116-38, 2014
3. Dalton HR et al: Hepatitis E. Curr Opin Infect Dis.
26(5):471-8, 2013
4. Jayakumar S et al: Fulminant viral hepatitis. Crit Care Clin.
29(3):677-97, 2013
5. Zhang J et al: Development of the hepatitis E vaccine: from
bench to field. Semin Liver Dis. 33(1):79-88, 2013
6. Lavanchy D: Viral hepatitis: global goals for vaccination. J
Clin Virol. 55(4):296-302, 2012
7. Matheny SC et al: Hepatitis A. Am Fam Physician.
86(11):1027-34; quiz 1010-2, 2012
8. Pavio N et al: Zoonotic hepatitis E: animal reservoirs and
emerging risks. Vet Res. 41(6):46, 2010
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Microscopic Features
A
Viral Infections: Viral Infections Requiring Ancillary Tests
HEPATITIS A AND E VIRUS INFECTIONS
(Left) Acute HAV infections
exhibit relatively nonspecific
findings. Zones 2 and 3
show a lobular hepatitis with
marked lobular disarray,
multiple foci of spotty
necrosis, and prominent
anisonucleosis. (Courtesy M.
Pittman, MD.) (Right) Acute
HAV infection shows zone 3
cholestasis with bile plugs.
The central vein (terminal
hepatic venule) does not
appear to be damaged.
(Courtesy M. Pittman, MD.)
(Left) A severe episode of
acute HAV infection shows a
cholestatic pattern of injury
around the central vein
with severe hepatocellular
necrosis, the so-called
"feathery" degeneration,
characteristic of biliary
injury. (Courtesy M. Pittman,
MD.) (Right) Acute HEV
infections exhibit panlobular
hepatitis. There is clear
interface hepatitis in the
small portal tract, with
hepatocellular disarray and
an inflammatory infiltrate
throughout the lobule.
(Courtesy J. Verheij, MD,
PhD.)
(Left) Acute HEV infection
shows interface hepatitis
with a mixed chronic
inflammatory infiltrate,
with surrounding swollen
hepatocytes. An acidophil
body is identified in the
lobule , next to a dilated
canaliculus with a pale
bile plug. (Courtesy J.
Verheij, MD, PhD.) (Right)
cute HEV infection is
characterized by nonspecific
features including acidophil
bodies, lobular inflammation,
and activated sinusoidal
Kupffer cells. (Courtesy J.
Verheij, MD, PhD.)
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11
HEPATITIS C VIRUS INFECTION
Macrovesicular steatosis is characteristic of but is
not diagnostic of chronic hepatitis C infection. (Courtesy
Viral Infections: Viral Infections Requiring Ancillary Tests
Franz von Lichtenberg Collection of Infectious Disease
Pathology, BWH.)
TERMINOLOGY
Abbreviations
Hepatitis C virus (HCV)
Synonyms
Non-A, non-B hepatitis
Definitions
Flavivirus family
From Latin "flavus" (yellow)
Hepacivirus genus
From Latin "hepa" (liver)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Transmitted parenterally (discovered in 1989)
Most commonly seen in intravenous drug users or
past users (60% of cases)
Increase in cases during 1980s through
contaminated blood transfusion products and organ
transplants prior to discovery and screening
1.8% risk of infection following occupational needle
stick injury
Sexual transmission
Vertical transmission from mother to child
Liver fibrosis and cirrhosis are due to active yet
ineffective immune response, which damages liver
tissue but fails to eradicate virus
Hepatocellular carcinoma develops in 2-5% of those
with hepatitis C-related cirrhosis
CLINICAL ISSUES
I
Epidemiology
Incidence
2
Periportal lymphoid aggregates and adjacent interface
hepatitis are shown with bile duct infiltration
, characteristic of hepatitis C. Patients are often
asymptomatic at this stage.
150 million people worldwide are estimated to be
infected chronically with hepatitis C virus
Prevalence ranges from 1.5% in developed countries
to ~ 3% in developing countries
Site
Liver
Extrahepatic manifestations
Cryoglobulinemia, glomerulonephritis, lichen
planus, lymphoproliferative disorders, Sjgren
syndrome
Can also be detected in peripherally circulating
monocytes, which are thought to be a major source of
recurrence in liver transplant recipients
Presentation
Acute hepatitis C
Majority are asymptomatic
Minority have vague symptoms including fatigue,
nausea, abdominal discomfort
Fulminant hepatic failure is extremely rare
Chronic hepatitis C
Often incidentally noted as elevated transaminases
with subsequent finding of HCV positivity
Rarely may present as decompensated liver cirrhosis
Laboratory Tests
Serology for anti-hepatitis C viral IgG antibodies with
enzyme immunoassay
If antibody test is positive, test is confirmed with HCV
RNA PCR
Liver function tests may show transaminitis
Natural History
85% of those infected will develop chronic HCV
infection
60-80% will develop chronic hepatitis
20-30% will develop cirrhosis
2-5% risk per year of developing hepatocellular
carcinoma once cirrhosis is established
12
HEPATITIS C VIRUS INFECTION
Etiology
Transmitted parenterally
Liver fibrosis and cirrhosis are due to active yet
ineffective immune response, which damages liver
tissue but fails to eradicate virus
Clinical Issues
150 million people worldwide are estimated to be
infected chronically with hepatitis C virus
85% of those infected will develop chronic hepatitis
C infection
20-30% will develop cirrhosis
2-5% risk per year of developing hepatocellular
carcinoma once cirrhosis is established
Treatment
Drugs
Interferon and ribavirin
Protease inhibitors: Boceprevir, telaprevir
Directly-acting antivirals: Sofosbuvir, ledipsavir
New targeted therapies have shown > 97%
sustained virologic response rates for treatment of
chronic hepatitis C infection
Prognosis
Staging of disease is based on degree of fibrosis present
Grading of disease is based on level of
necroinflammatory activity and is more accurate at
predicting progression than stage, with higher levels of
necroinflammatory activity having poorer prognosis
Response to interferon-based therapy is ~ 50%
Reinfection of donor liver following transplant for
end-stage liver disease is universal and these patients
can undergo accelerated course to cirrhosis, with up to
25% developing cirrhosis 5-10 years post transplant
MICROBIOLOGY
Virus Features
Enveloped, positive-stranded RNA virus (Flavivirus)
9.6 Kb genome with a single ORF
Viral Culture
Cell culture-derived HCV system in human hepatoma
cell lines
Replicons of HCV RNA in hepatoma cell lines
HCV pseudoparticles culture system
MICROSCOPIC PATHOLOGY
Histologic Features
Acute hepatitis
Ballooning degeneration, apoptosis
Cholestasis, macrophage aggregates
Chronic hepatitis
Key Facts
Microscopic Pathology
Lymphoid aggregates in portal tracts are a hallmark
feature
Steatosis
Interface hepatitis in more severe cases with
inflammation extending to periportal parenchyma
Cirrhosis: Regenerative nodules of hepatocytes with
intervening bands of fibrosis
Diagnostic Checklist
Grading of disease is based on inflammation
Staging of disease is based on fibrosis
Cryoglobulinemia
DIFFERENTIAL DIAGNOSIS
Viral Hepatitis
Serological discrimination between hepatitis A/B/D/E
Hepatitis A and E are associated with travel and food
contamination
Hepatitis B and D are also associated with parenteral
infection but lack steatosis
Autoimmune Hepatitis
Serological discrimination; anti-nuclear antibodies
(ANA), anti-smooth muscle antibodies (SMA), antiliver kidney microsome type 1 antibodies (LKM-1)
Lack of exposure history
Drug-Induced Hepatitis
Drug history
Presence of eosinophils
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Grading of inflammation (Batts-Ludwig grading scale),
staging of fibrosis (Metavir scale)
SELECTED REFERENCES
1. Yamane D et al: Liver injury and disease pathogenesis
Lymphoid aggregates in portal tracts and steatosis
Interface hepatitis in more severe cases with
inflammation extending to periportal parenchyma
Deposition of fibrous tissue, beginning in portal
tracts and leading to septal fibrosis
Cirrhosis: Regenerative nodules of hepatocytes with
intervening bands of fibrosis
Dense deposits are seen in glomeruli via IF or EM
in chronic hepatitis C. Curr Top Microbiol Immunol.
369:263-88, 2013
Viral Infections: Viral Infections Requiring Ancillary Tests
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Gross and Microscopic Features
p
p
p
p
(Left) Chronic lymphocytic
inflammation in the
eriportal region of a liver
shows damage with loss of
hepatocytes
areas of macrovesicular
steatosis . (Right) Periportal
inflammation in a hepatitis
C liver biopsy demonstrates
steatosis and dense
lymphocytic inflammation in
the periportal region . Note
the loss of hepatocytes and
extension of inflammation into
arenchyma.
Viral Infections: Viral Infections Requiring Ancillary Tests
(Left) Inflammation, seen
as a lymphoid aggregate,
in a liver biopsy from
a hepatitis C patient
demonstrates penetration
into hepatic parenchyma and
hepatocyte necrosis. (Right)
Macrovesicular hepatosteatosis
is characteristic of, but not
athognomonic for, chronic
hepatitis C infection. Note the
lymphocytic inflammatory
cells around the portal
regions and extending into the
arenchyma. (Courtesy Franz
von Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
and scattered
HEPATITIS C VIRUS INFECTION
(Left) Autopsied liver of
a patient with end-stage
liver disease demonstrates
micronodular cirrhosis .
Distinctively suspicious areas
for hepatocellular carcinoma
are not seen in this case,
but cirrhosis is diffuse with
minimal normal parenchyma.
(Right) Trichrome stain of a
liver with chronic hepatitis
C infection demonstrates
cirrhosis, seen as bands of
bridging fibrosis with
intervening regenerative
hepatic nodules .
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HEPATITIS C VIRUS INFECTION
p
p
g
Gross and Microscopic Features
Viral Infections: Viral Infections Requiring Ancillary Tests
(Left) Liver section from
an autopsy of a patient
with end-stage liver disease
demonstrates macronodular
cirrhosis with prominent
fibrosis . Careful
examination for potential
nodules of hepatocellular
carcinoma is required,
especially when borders
appear infiltrative or distinct.
(Right) Trichrome stain of
liver with chronic hepatitis
C infection shows cirrhosis
characterized by many
bands of bridging fibrosis
with mostly intervening
regenerative hepatic nodules
.
(Left) A liver core biopsy
from a patient with
longstanding hepatitis
C demonstrates a
seudoglandular pattern,
lack of portal triads, and
cords of hepatocytes > 2
layers thick, consistent with
hepatocellular carcinoma.
(Right) The pseudoglandular
attern and thick cords
of hepatocytes seen
here are consistent with
hepatocellular carcinoma.
(Left) Immunofluorescence
demonstrates glomerular
dense deposits in the
kidney as a result of HCVassociated cryoglobulinemia.
(Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.) (Right) Electron
micrograph demonstrates
lomerular dense deposits
as a result of hepatitis Cassociated cryoglobulinemia
. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
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