Chronic Liver Diseases
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Transcript of Chronic Liver Diseases
CHRONIC LIVER CHRONIC LIVER DISEASES & PLCCDISEASES & PLCC
Dr G.O OGUNDr G.O OGUNDept of PathologyDept of Pathology
College of MedicineCollege of MedicineUniversity of IbadanUniversity of Ibadan
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IntroductionIntroduction Is liver disease that persist over many Is liver disease that persist over many
months without progressive months without progressive improvement towards normalcy of improvement towards normalcy of usually the architecture.usually the architecture.
May follow acute disease with May follow acute disease with manifestation been insidious manifestation been insidious
Time interval- >6weeksTime interval- >6weeks The degree of hepatic dysfunction The degree of hepatic dysfunction
varies widely and can vary from varies widely and can vary from asymptomatic to symptomatic.asymptomatic to symptomatic.
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AETIOLOGYAETIOLOGY Chronic hepatitis+Chronic hepatitis+ Hepatic Cirrhosis+*Hepatic Cirrhosis+* SchistosomiasisSchistosomiasis Alcoholic liver diseaseAlcoholic liver disease Liver cell carcinoma+*Liver cell carcinoma+* HaemochromatosisHaemochromatosis Alpha-1-antitrypsin deficiencyAlpha-1-antitrypsin deficiency Wilson’s diseaseWilson’s disease Primary biliary cirrhosisPrimary biliary cirrhosis Chronic biliary obstructionChronic biliary obstruction*Hepatic cirrhosis and liver cell carcinoma are *Hepatic cirrhosis and liver cell carcinoma are
stages in liver damage common to many stages in liver damage common to many aetiologies.aetiologies.
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Chronic HepatitisChronic Hepatitis Is defined as symptomatic, biochemical or Is defined as symptomatic, biochemical or
serologic evidence of continuing or serologic evidence of continuing or relapsing hepatic disease for more than 6 relapsing hepatic disease for more than 6 months with histological documentation of months with histological documentation of inflammation and necrosis.inflammation and necrosis.
HBV,HCV and HBV+HDV are responsible for HBV,HCV and HBV+HDV are responsible for most chronic hepatitismost chronic hepatitis
Other aetiologies – Drugs- INH, alpha Other aetiologies – Drugs- INH, alpha methyl dopa, methotrexate and methyl dopa, methotrexate and autoimmunityautoimmunity
In all cases of chronic hepatitis, aetiology is In all cases of chronic hepatitis, aetiology is the single most important indicator of the single most important indicator of likelihood of progression to cirrhosis.likelihood of progression to cirrhosis. 44
Viral Hepatitis: Viral Hepatitis: MicrobiologyMicrobiologyVirusVirus Hep-AHep-A Hep-BHep-B Hep-CHep-C
agentagent ssRNAssRNA dsDNAdsDNA ssRNAssRNA
Transm.Transm. Feco-Feco-oraloral
Parenteral, Parenteral, close contactclose contact
ParenteralParenteral, close , close contcont
Carrier Carrier statestate
NoneNone 0.1-1.0%0.1-1.0% 0.2-1.0%0.2-1.0%
Chronic Chronic HepatitisHepatitis
NoneNone 5-10% of acute 5-10% of acute infectioninfection
>50%>50%
HCCHCC NoNo YesYes YesYes55
Hepatitis C Virus
The non-A, non-B factor 66
Picture credit: http://www.info.gov.hk/hepatitis/images/fig07.gif 77
HBVHBV Is a hardy virus and can survive extreme Is a hardy virus and can survive extreme
temperature and humidity.temperature and humidity. 350 million world wide carrier rate, 2 350 million world wide carrier rate, 2
billion of people alive has come in contact billion of people alive has come in contact with it. with it.
Blood and body fluid are primary sources Blood and body fluid are primary sources of infection- also- semen, saliva, sweat, of infection- also- semen, saliva, sweat, tears, breast milktears, breast milk
Vertical transmission from infected mother Vertical transmission from infected mother to neonate is common in Africa and Asia to neonate is common in Africa and Asia leading to carrier state for lifeleading to carrier state for life
Circulating host IgG antibodies neutralises Circulating host IgG antibodies neutralises HBV, vaccination has been highly effective HBV, vaccination has been highly effective in reducing the prevalence in endemic in reducing the prevalence in endemic areas of the world. e.g Taiwan example.areas of the world. e.g Taiwan example.
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99
Normal Liver - MicroscopyNormal Liver - Microscopy
1010
Chronic hepatitis - 2Chronic hepatitis - 2
Chronic viral hepatitis constitutes a “carrier” Chronic viral hepatitis constitutes a “carrier” state because the patient harbor replicating state because the patient harbor replicating virus and can transmit the organism.virus and can transmit the organism.
Patients can eitherPatients can either1.1. Habor the virus but suffers little or no Habor the virus but suffers little or no
adverse effect.adverse effect.2.2. Those with chronic hepatitis by laboratory Those with chronic hepatitis by laboratory
and histologic findings but are symptom freeand histologic findings but are symptom free3.3. Those with clinically symptomatic chronic Those with clinically symptomatic chronic
disease.disease.
1111
VirusesChronic Hepatitis C
Usually asymptomatic
• Route of infection– IV drugs (80%)
– Blood products
– Unknown
– Needle stick
– Vertical transmission
• Diagnosis– Hepatitis C Ab (IgG)
– HCV RNA
– ALT raised
• Complications– Chronic infection
– Cirrhosis
20% resolves spontaneously1212
Chronic Hepatitis C
• Advise to patient– Alcohol < 10u/week
– Do not share razors
– Normal lifestyle
Infection
Cirrhosis
DecompensatedCirrhosis
Liver failure (death or transplant)
30 yrs
5-15yrs
1-2yrs Interferon/Ribavirin
55% cure
1313
1414
Morphology - AcuteMorphology - Acute Tissue alteration caused by acute infection Tissue alteration caused by acute infection
with HAV,HBV,HCV,HEV are similarwith HAV,HBV,HCV,HEV are similar HBV- infected hepatocytes – ground glass HBV- infected hepatocytes – ground glass
appearance- due to spheres and tubules of appearance- due to spheres and tubules of HBsAg packed in the cytoplasm- appears HBsAg packed in the cytoplasm- appears eosinophilic.eosinophilic.
HCV- infected liver shows lymphoid aggregates HCV- infected liver shows lymphoid aggregates within the portal tract and sublobular within the portal tract and sublobular macrosteatosis.macrosteatosis.
Interphase hepatitis- Is when inflammation Interphase hepatitis- Is when inflammation spill over from the portal tract into adjacent spill over from the portal tract into adjacent parenchyma to cause necrosis of the periportal parenchyma to cause necrosis of the periportal hepatocytes – occurs in both acute and hepatocytes – occurs in both acute and chronic.chronic.
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MORPHOLOGY-ChronicMORPHOLOGY-Chronic In the mild forms, significant inflammation is In the mild forms, significant inflammation is
limited to the portal tract and consist of limited to the portal tract and consist of lymphocytes, macrophages, occasional plasma lymphocytes, macrophages, occasional plasma cells and rarely neutrophils and eosinophils.cells and rarely neutrophils and eosinophils.
In mild chronic HCV- lymphoid aggregates and In mild chronic HCV- lymphoid aggregates and bile duct damage in the portal tracts and mild bile duct damage in the portal tracts and mild to moderate macrovesicular steatosis.to moderate macrovesicular steatosis.
HBV- “Ground glass hepatocyte”, “sanded” HBV- “Ground glass hepatocyte”, “sanded” nucleinuclei
In all form of chronic hepatitis, continued In all form of chronic hepatitis, continued INTERPHASE hepatitis and BRIDGING INTERPHASE hepatitis and BRIDGING inflammation and necrosis are sign of inflammation and necrosis are sign of progressive liver damage.progressive liver damage.
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Morphology –Chronic -contdMorphology –Chronic -contd
The hallmark of irreversible liver The hallmark of irreversible liver damage is the deposition of fibrous damage is the deposition of fibrous tissue.tissue.
Initially affect only the portal tract, Initially affect only the portal tract, then periportal septal fibrosis, then then periportal septal fibrosis, then linkage of fibrous septal between linkage of fibrous septal between lobules ( bringing fibrosis.lobules ( bringing fibrosis.
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Acute viral Hepatitis:Acute viral Hepatitis:
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Acute viral Hepatitis:Acute viral Hepatitis:
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Acute viral Hepatitis:Acute viral Hepatitis:
2020
Liver Biopsy – viral Hepatitis-CLiver Biopsy – viral Hepatitis-C
2121
Liver Biopsy - CAH:Liver Biopsy - CAH:
2222
Liver Biopsy – CPH:Liver Biopsy – CPH:
2323
CIRRHOSISCIRRHOSIS
Is a chronic liver disease characterised byIs a chronic liver disease characterised by
1.1. Diffuse involvement of the liverDiffuse involvement of the liver
2.2. Complete loss and distruption of the Complete loss and distruption of the architecture of the liverarchitecture of the liver
3.3. Extensive bridging fibrous septae/fibrosisExtensive bridging fibrous septae/fibrosis
4.4. Regenerating parenchymal nodules with Regenerating parenchymal nodules with diameter varying from very small (<3mm, diameter varying from very small (<3mm, micronodules) to larger of several micronodules) to larger of several cm(Macro)cm(Macro) 2424
CIRRHOSIS- 2CIRRHOSIS- 2
Cirrhosis is common end result of many Cirrhosis is common end result of many chronic liver disorders.chronic liver disorders.
Diffuse scarring of liver – follows Diffuse scarring of liver – follows hepatocellular necrosis of hepatitis.hepatocellular necrosis of hepatitis.
Inflammation – healing with fibrosis - Inflammation – healing with fibrosis - Regeneration of remaining hepatocytes Regeneration of remaining hepatocytes form regenerating nodules.form regenerating nodules.
Loss of normal architecture & function.Loss of normal architecture & function.
2525
CIRRHOSIS -3CIRRHOSIS -3 Vascular architecture is reorganized by Vascular architecture is reorganized by
the parenchymal damage and scarring the parenchymal damage and scarring with formation of abnormal with formation of abnormal interconnections between vascular interconnections between vascular inflow and hepatic vein outflow inflow and hepatic vein outflow channels thus portal and arterial blood channels thus portal and arterial blood by passes the liver.by passes the liver.
Fibrosis is key feature of progressive Fibrosis is key feature of progressive damage to the liverdamage to the liver
Once cirrhosis is established, it is usually Once cirrhosis is established, it is usually impossible to establish an aetiology on impossible to establish an aetiology on morphologic grounds alone.morphologic grounds alone. 2626
Normal LiverNormal Liver
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CirrhosisCirrhosis
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Normal Liver HistologyNormal Liver Histology
CV
PT
2929
CirrhosisCirrhosis
Fibrosis
Regenerating Nodule
3030
AETIOLOGY OF CIRRHOSIS (OUR AETIOLOGY OF CIRRHOSIS (OUR ENVIRONMENT)ENVIRONMENT)
HBV infection (chronic) –high prevalence HBV infection (chronic) –high prevalence presumedpresumed
HCV,HDV (chronic)- high prevalence HCV,HDV (chronic)- high prevalence presumedpresumed
AlcoholicAlcoholic CryptogenicCryptogenic Hereditary, immunologic, metabolic- Hereditary, immunologic, metabolic-
alpha antitrypsin deficiency, alpha antitrypsin deficiency, Primary haemochromatosis, Wilsons disease, Primary haemochromatosis, Wilsons disease, galactosaemia, primary biliary cirrhosisgalactosaemia, primary biliary cirrhosis
3131
Aetiology of Cirrhosis ( Western Aetiology of Cirrhosis ( Western World)World)
Alcoholic liver diseaseAlcoholic liver disease 60-70%60-70% Viral hepatitisViral hepatitis 10%10% Biliary diseaseBiliary disease 5-10%5-10% Primary hemochromatosisPrimary hemochromatosis 5%5% Cryptogenic cirrhosisCryptogenic cirrhosis 10-15%10-15% Wilson’s, Wilson’s, 1AT def1AT def rarerare
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Pathogenesis:Pathogenesis: Hepatocyte injury leading to necrosis.Hepatocyte injury leading to necrosis.
– Alcohol, virus, drugs, toxins, genetic etc..Alcohol, virus, drugs, toxins, genetic etc.. Chronic inflammation - Chronic inflammation - (hepatitis).(hepatitis).
Bridging fibrosis.Bridging fibrosis. Regeneration of remaining hepatocytes Regeneration of remaining hepatocytes
Proliferating as round nodules.Proliferating as round nodules. Loss of vascular arrangement results in Loss of vascular arrangement results in
regenerating hepatocytes which are regenerating hepatocytes which are ineffective.ineffective.
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Pathogenesis-2Pathogenesis-2 Main source of collagen in cirrhosis is the Main source of collagen in cirrhosis is the
interstitial cells of Ito in the space of Disse interstitial cells of Ito in the space of Disse – Normally stores retinal- Vit A– Normally stores retinal- Vit A
Normally type I and III collagen are around Normally type I and III collagen are around the portal tract and the central veinthe portal tract and the central vein
In cirrhosis both are deposited in the In cirrhosis both are deposited in the lobuleslobules
Chronic inflammation – TNF,IL1,lyphotoxinChronic inflammation – TNF,IL1,lyphotoxin Activated Kupffer cells, endothelial cells, Activated Kupffer cells, endothelial cells,
hepatocytes, bile duct epthelial cell- hepatocytes, bile duct epthelial cell- PDGF,TGF BetaPDGF,TGF Beta
Ito cells transform to MyofibroblastsIto cells transform to Myofibroblasts 3434
Macronodular CirrhosisMacronodular Cirrhosis
3535
Alcoholic CirrhosisAlcoholic Cirrhosis
3636
Liver Biopsy – CirrhosisLiver Biopsy – Cirrhosis
3737
Liver Biopsy – Cirrhosis:Liver Biopsy – Cirrhosis:
3838
Nutmeg Liver-Cardiac SclerosisNutmeg Liver-Cardiac Sclerosis
3939
4040
Clinical featuresClinical features
Gynaecomastia –in menGynaecomastia –in men Oligomenorrhea, amenorrhea, Oligomenorrhea, amenorrhea,
sterility- in womensterility- in women
4141
Complications:Complications: Congestive spleenomegaly.Congestive spleenomegaly. Spontaneous bacteria peritonitisSpontaneous bacteria peritonitis Bleeding varices.Bleeding varices. Hepatocellular failure.Hepatocellular failure.
– Hepatic encephalitis / hepatic Hepatic encephalitis / hepatic coma.coma.
Hepatocellular carcinoma.Hepatocellular carcinoma.
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Alcoholic Liver Disease
Alcohol ExcessNormal
Hepatitis
Fibrosis
Cirrhosis
Steatosis
Elevated GGT
High PT and low albumin Elevated bilirubin
Elevated GGT +/- AST
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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
4444
Chronic Liver DiseaseBiliary Disease
Primary biliary cirrhosis
• Background– Small bile ducts
damage
– 90% Females
• Presentation– Itching
– Abnormal liver tests
– Complications of cirrhosis (rare)
• Investigations– ALP/GGT +++
– Antimitochondrial Ab+
– Liver biopsy
• Complications– Jaundice (late)
– Progression to cirrhosis
– 10-15yrs
4545
Chronic Liver DiseaseBiliary disease
Primary sclerosing cholangitis
Associated Ulcerative colitisComplication Cholangiocarcinoma
4646
Primary Liver cell carcinomaPrimary Liver cell carcinoma Hepatocellular carcinomaHepatocellular carcinoma CholangiocarcinomaCholangiocarcinoma Hepatocellular carcinoma has a wide Hepatocellular carcinoma has a wide
variation in various parts of the world.variation in various parts of the world. Constitute 5.4% of cancers world wide.Constitute 5.4% of cancers world wide. Annual incidence range from 5- 36 per Annual incidence range from 5- 36 per
100,000100,000 Highest incidence in korea, Taiwan, Highest incidence in korea, Taiwan,
Mozambique, South eastern China.Mozambique, South eastern China. Black are attack rates 3x that of CaucasiansBlack are attack rates 3x that of Caucasians M>F ; 1.5-3: 1 M>F ; 1.5-3: 1 85% of HCC occur in countries with high rates 85% of HCC occur in countries with high rates
of HBV infectionof HBV infection 4747
AETIOLOGYAETIOLOGY HBV- HBV chronic carrier state*HBV- HBV chronic carrier state* HCV- Anti- HCV seropositive status*HCV- Anti- HCV seropositive status* Chronic Alcoholism*Chronic Alcoholism* Food contaminants* (primarily Food contaminants* (primarily
Alflatoxin – Aspergillus Flavus in Alflatoxin – Aspergillus Flavus in grains and also Fusarium moniloforme grains and also Fusarium moniloforme in maize.in maize.
NitrosaminesNitrosamines TyrosinaemiaTyrosinaemia Hereditary haemochromatosis.Hereditary haemochromatosis. 4848
PathogenesisPathogenesis Extensive epidemiologic studies link HBV and Extensive epidemiologic studies link HBV and
chronic HCV infection with liver cell cancer.chronic HCV infection with liver cell cancer. The development of cirrhosis is important but not The development of cirrhosis is important but not
requisite for the development of HCC.requisite for the development of HCC. Viral DNA is integrated into host genome.Viral DNA is integrated into host genome. HBV cause chronic liver damage and regenerative HBV cause chronic liver damage and regenerative
hyperplasiahyperplasia HBV expands the pool of cycling cells at risk for HBV expands the pool of cycling cells at risk for
subsequent genetic changes.subsequent genetic changes. HBV encodes a regulatory protein HBV encodes a regulatory protein HBx.HBx. HBx HBx distrupts normal growth control of infected distrupts normal growth control of infected
liver cells by activation of several growth liver cells by activation of several growth promoting genes such as Insulin- like Growth promoting genes such as Insulin- like Growth Factor I.Factor I.
HBx HBx also binds p53 and interferes with its growth also binds p53 and interferes with its growth suppressing activity.suppressing activity.
HCV- related to the chronic inflammation.HCV- related to the chronic inflammation.4949
MORPHOLOGYMORPHOLOGY UnifocalUnifocal MultifocalMultifocal Diffusely infilterativeDiffusely infilterative FibrolamellarFibrolamellar Often background cirrhosis or chronic hepatitisOften background cirrhosis or chronic hepatitis Histology- Well differentiated to anaplasticHistology- Well differentiated to anaplastic Strong propensity for vascular invasionStrong propensity for vascular invasion HCC spread within the liver by continuous HCC spread within the liver by continuous
growth and development of satellite nodulesgrowth and development of satellite nodules Haematogenous metastasis especially to the Haematogenous metastasis especially to the
lungslungs
5050
5151
5252
5353
5454
DiagnosisDiagnosis
Clinical historyClinical history Biopsy/HistologyBiopsy/Histology Elevated alpha fetoprotein- in 50-Elevated alpha fetoprotein- in 50-
70% of patients with HCC70% of patients with HCC UltrasonographyUltrasonography CT, MRI, Hepatic angiographyCT, MRI, Hepatic angiography
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ComplicationsComplications
Rupture of tumour with associated Rupture of tumour with associated fatal haemorrhagefatal haemorrhage
GI/Esophageal variceal bleedingGI/Esophageal variceal bleeding Hepatic failure/comaHepatic failure/coma
5656