CHRONIC LIVER

DISEASES & PLCC

Dr G.O OGUN
Dept of Pathology
College of Medicine
University of Ibadan

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 Introduction
 Isliver disease that persist over many
months without progressive
improvement towards normalcy of
usually the architecture.
 May follow acute disease with
manifestation been insidious
 Time interval- >6weeks
 The degree of hepatic dysfunction
varies widely and can vary from
asymptomatic to symptomatic.
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 AETIOLOGY
 Chronic hepatitis+
 Hepatic Cirrhosis+*
 Schistosomiasis
 Alcoholic liver disease
 Liver cell carcinoma+*
 Haemochromatosis
 Alpha-1-antitrypsin deficiency
 Wilson’s disease
 Primary biliary cirrhosis
 Chronic biliary obstruction
*Hepatic cirrhosis and liver cell carcinoma are
stages in liver damage common to many 3
 Chronic Hepatitis
 Is defined as symptomatic, biochemical or
serologic evidence of continuing or
relapsing hepatic disease for more than 6
months with histological documentation of
inflammation and necrosis.
 HBV,HCV and HBV+HDV are responsible
for most chronic hepatitis
 Other aetiologies – Drugs- INH, alpha
methyl dopa, methotrexate and
autoimmunity
 In all cases of chronic hepatitis, aetiology
is the single most important indicator of
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likelihood of progression to cirrhosis.
 Viral Hepatitis: Microbiology
Virus Hep-A Hep-B Hep-C

agent ssRNA dsDNA ssRNA

Transm. Feco- Parenteral, Parenteral

oral close contact , close
Carrier None 0.1-1.0% cont
0.2-1.0%
state
Chronic None 5-10% of acute >50%
Hepatitis infection
HCC No Yes Yes 5
Hepatitis C Virus

The non-A, non-B factor 6

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 Picture credit:
 HBV
 Is a hardy virus and can survive extreme
temperature and humidity.
 350 million world wide carrier rate, 2
billion of people alive has come in contact
with it.
 Blood and body fluid are primary sources
of infection- also- semen, saliva, sweat,
tears, breast milk
 Vertical transmission from infected mother
to neonate is common in Africa and Asia
leading to carrier state for life
 Circulating host IgG antibodies neutralises
HBV, vaccination has been highly effective
in reducing the prevalence in endemic 8
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Normal Liver - Microscopy

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 Chronic hepatitis - 2
 Chronic viral hepatitis constitutes a
“carrier” state because the patient
harbor replicating virus and can
transmit the organism.
 Patients can either
3. Habor the virus but suffers little or no
adverse effect.
4. Those with chronic hepatitis by
laboratory and histologic findings but
are symptom free
5. Those with clinically symptomatic 11
 Viruses
Chronic Hepatitis C
Usually asymptomatic • Diagnosis
– Hepatitis C Ab (IgG)
• Route of infection – HCV RNA
– IV drugs (80%) – ALT raised
– Blood products • Complications
– Unknown – Chronic infection
– Needle stick – Cirrhosis
– Vertical transmission

20% resolves spontaneously

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 Chronic Hepatitis C
Infection • Advise to patient
30 yrs – Alcohol < 10u/week
– Do not share razors
Cirrhosis – Normal lifestyle
5-15yrs

Decompensated
Cirrhosis
1-2yrs Interferon/Ribavirin

Liver failure 55% cure

(death or transplant)
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 Morphology - Acute
 Tissue alteration caused by acute infection
with HAV,HBV,HCV,HEV are similar
 HBV- infected hepatocytes – ground glass
appearance- due to spheres and tubules of
HBsAg packed in the cytoplasm- appears
eosinophilic.
 HCV- infected liver shows lymphoid
aggregates within the portal tract and
sublobular macrosteatosis.
 Interphase hepatitis- Is when inflammation
spill over from the portal tract into adjacent
parenchyma to cause necrosis of the
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periportal hepatocytes – occurs in both
 MORPHOLOGY-Chronic
 In the mild forms, significant inflammation is
limited to the portal tract and consist of
lymphocytes, macrophages, occasional
plasma cells and rarely neutrophils and
eosinophils.
 In mild chronic HCV- lymphoid aggregates
and bile duct damage in the portal tracts and
mild to moderate macrovesicular steatosis.
 HBV- “Ground glass hepatocyte”, “sanded”
nuclei
 In all form of chronic hepatitis, continued
INTERPHASE hepatitis and BRIDGING 16
Morphology –Chronic -contd
 The hallmark of irreversible liver
damage is the deposition of fibrous
tissue.
 Initially affect only the portal tract,
then periportal septal fibrosis, then
linkage of fibrous septal between
lobules ( bringing fibrosis.

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Acute viral Hepatitis:

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Acute viral Hepatitis:

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Acute viral Hepatitis:

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Liver Biopsy – viral Hepatitis-C

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Liver Biopsy - CAH:

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Liver Biopsy – CPH:

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 CIRRHOSIS
 Is a chronic liver disease characterised
by

3. Diffuse involvement of the liver

4. Complete loss and distruption of the
architecture of the liver
5. Extensive bridging fibrous
septae/fibrosis
6. Regenerating parenchymal nodules with 24
 CIRRHOSIS- 2
 Cirrhosis is common end result of
many chronic liver disorders.
 Diffuse scarring of liver – follows
hepatocellular necrosis of hepatitis.
 Inflammation – healing with fibrosis
- Regeneration of remaining
hepatocytes form regenerating
nodules.
 Loss of normal architecture &
function. 25
 CIRRHOSIS -3
 Vascular architecture is reorganized
by the parenchymal damage and
scarring with formation of abnormal
interconnections between vascular
inflow and hepatic vein outflow
channels thus portal and arterial
blood by passes the liver.
 Fibrosis is key feature of progressive
damage to the liver
 Once cirrhosis is established, it is
usually impossible to establish an 26
Normal Liver

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Cirrhosis

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Normal Liver Histology

CV

PT

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 Cirrhosis

Fibrosis

Regenerating Nodule

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 AETIOLOGY OF CIRRHOSIS (OUR
ENVIRONMENT)
 HBV infection (chronic) –high prevalence
presumed
 HCV,HDV (chronic)- high prevalence
presumed
 Alcoholic
 Cryptogenic
 Hereditary, immunologic, metabolic-
alpha antitrypsin deficiency,
Primary haemochromatosis, Wilsons
disease, galactosaemia, primary biliary
cirrhosis 31
Aetiology of Cirrhosis ( Western
World)
 Alcoholic liver disease 60-70%
 Viral hepatitis 10%
 Biliary disease 5-10%
 Primary hemochromatosis 5%
 Cryptogenic cirrhosis 10-15%
 Wilson’s, α1AT def rare

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 Pathogenesis:
 Hepatocyte injury leading to necrosis.
– Alcohol, virus, drugs, toxins, genetic etc..
 Chronic inflammation - (hepatitis).
 Bridging fibrosis.
 Regeneration of remaining hepatocytes
Proliferating as round nodules.
 Loss of vascular arrangement results in
regenerating hepatocytes which are
ineffective.
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 Pathogenesis-2
 Main source of collagen in cirrhosis is the
interstitial cells of Ito in the space of Disse
– Normally stores retinal- Vit A
 Normally type I and III collagen are around
the portal tract and the central vein
 In cirrhosis both are deposited in the
lobules
 Chronic inflammation – TNF,IL1,lyphotoxin
 Activated Kupffer cells, endothelial cells,
hepatocytes, bile duct epthelial cell-
PDGF,TGF Beta
 Ito cells transform to Myofibroblasts 34
Macronodular Cirrhosis

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Alcoholic Cirrhosis

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Liver Biopsy – Cirrhosis

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Liver Biopsy – Cirrhosis:

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Nutmeg Liver-Cardiac Sclerosis

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 Clinical features
 Gynaecomastia –in men
 Oligomenorrhea, amenorrhea,
sterility- in women

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 Complications:
 Congestive spleenomegaly.
 Spontaneous bacteria peritonitis
 Bleeding varices.
 Hepatocellular failure.
– Hepatic encephalitis / hepatic
coma.
 Hepatocellular carcinoma.

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 Alcoholic Liver Disease
Alcohol Excess
Normal
Elevated GGT
Fibrosis
Steatosis

Hepatitis
Cirrhosis

Elevated GGT +/- AST

High PT and low albumin Elevated bilirubin 43

 Alcoholic Hepatitis
 May be initial presentation of liver disease
 Presents with jaundice
 Liver function tests mixed pattern (ALP
450 (250) + ALT 100 (50)
 Cirrhosis usually present (+ complications)
 High mortality
– 20-50%
– May worsen on admission
– 1-6 months resolution

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 Chronic Liver Disease
Biliary Disease
Primary biliary cirrhosis

• Background • Investigations
– Small bile ducts – ALP/GGT +++
damage – Antimitochondrial Ab+
– 90% Females – Liver biopsy
• Presentation
– Itching • Complications
– Abnormal liver tests – Jaundice (late)
– Complications of – Progression to cirrhosis
cirrhosis (rare) – 10-15yrs

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 Chronic Liver Disease
Biliary disease
Primary sclerosing cholangitis

Associated Ulcerative colitis

Complication Cholangiocarcinoma

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Primary Liver cell carcinoma
 Hepatocellular carcinoma
 Cholangiocarcinoma
 Hepatocellular carcinoma has a wide
variation in various parts of the world.
 Constitute 5.4% of cancers world wide.
 Annual incidence range from 5- 36 per
100,000
 Highest incidence in korea, Taiwan,
Mozambique, South eastern China.
 Black are attack rates 3x that of
Caucasians
 M>F ; 1.5-3: 1 47
 AETIOLOGY
 HBV- HBV chronic carrier state*
 HCV- Anti- HCV seropositive status*
 Chronic Alcoholism*
 Food contaminants* (primarily
Alflatoxin – Aspergillus Flavus in
grains and also Fusarium moniloforme
in maize.
 Nitrosamines
 Tyrosinaemia
 Hereditary haemochromatosis. 48
 Pathogenesis
 Extensive epidemiologic studies link HBV and
chronic HCV infection with liver cell cancer.
 The development of cirrhosis is important but not
requisite for the development of HCC.
 Viral DNA is integrated into host genome.
 HBV cause chronic liver damage and regenerative
hyperplasia
 HBV expands the pool of cycling cells at risk for
subsequent genetic changes.
 HBV encodes a regulatory protein HBx.
 HBx distrupts normal growth control of infected
liver cells by activation of several growth
promoting genes such as Insulin- like Growth
Factor I.
 HBx also binds p53 and interferes with its growth
suppressing activity. 49
 HCV- related to the chronic inflammation.
 MORPHOLOGY
 Unifocal
 Multifocal
 Diffusely infilterative
 Fibrolamellar
 Often background cirrhosis or chronic
hepatitis
 Histology- Well differentiated to anaplastic
 Strong propensity for vascular invasion
 HCC spread within the liver by continuous
growth and development of satellite nodules
 Haematogenous metastasis especially to the
lungs
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 Diagnosis
 Clinicalhistory
 Biopsy/Histology
 Elevated alpha fetoprotein- in 50-
70% of patients with HCC
 Ultrasonography
 CT, MRI, Hepatic angiography

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 Complications
 Rupture of tumour with associated
fatal haemorrhage
 GI/Esophageal variceal bleeding
 Hepatic failure/coma

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