hepatitis acute chronc liver

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Hepatitis Acute Chronic Liver disease

• Prof Y Mgonda

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DISEASE OF THE LIVER

• The Liver
• The Liver is the Largest organ of the body
• Weight 1.0 -1.5Kg (1.5-2.5 of lean body mass)
• (but the average Human Skin weighs 6-9 Kg!!!)
• The liver has dual blood supply
• Hepatic artery 20
• O2 rich
• Portal vein 80
• Nutrient rich

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The liver ct

• Cytology
• Hepatocytes
• Majority
• Other cells
• Kupffer cells (RES),
• Hepatic Stellate Cells
• Formally known as
• Fat storing cells,
• Lipocytes,
• Perisinusoidal cells

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Functions of the Liver The Hepatocyte functions

• Numerous and vital functions
• 1. Synthesis function
• It is Essential site for synthesis of serum
  proteins
• Albumin
• Carrier proteins
• Coagulation factors
• Hormones
• Growth factors

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Hepatocyte functions ct.

• 2. Production function
• Bile and its carriers
• Bile acids
• cholesterol
• 3. Regulation of nutrients function
• Glucose
• Glycogen
• Amino acids
• Lipids

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• 4. Metabolism and conjugation of
• Lipophilic compounds for excretion in urine
• Bile
• Bilirubin
• Anions
• Cations
• Drugs
• Hormones
• Clinically utilized as
• Liver Function Tests (LFTs)

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Liver Function Tests

• Summary of Commonly used LFTs
• Serum bilirubin
• Total and differential
• Measure of
• Hepatic conjugation function
• Hepatic excretory function
• Serum albumin
• Measure of
• Protein synthesis
• Prothrombin time
• Measure of
• Protein synthesis

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Clinical application of LFTs

• Measures of hepatocyte function
• e.g. Serum albumin level
• Disease or loss of hepatocytes will show
• Defective albumin synthesis
• Low serum albumin level
• Measures of hepatocyte destruction
• Serum Alanine Amino Transferase ALT
• Elevated serum level of ALT indicates
• Hepatocyte destruction

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Spectrum of Diseases of the Liver

• Liver disease spectrum consists of
• Inflammation/Hepatitis Fibrosis Chronic
  hepatitis Cirrhosis
• Chronic Liver Failure Hepatocellular Carcinoma
  Death
• Acute Hepatitis
• Fulminant hepatitis
• Acute liver failure
• Fibrosis
• Chronic hepatitis
• Liver Cirrhosis
• CHRONIC LIVER FAILURE
• HEPATOCELLULAR CARCINOMA
• Some may ultimately require
• Liver transplant
• All will ultimately proceed to
• DEATH

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Diseases of the liver Hepatitis

• Definition
• Inflammation of liver cell (tissue)/parenchyma
• Etiological classification
• Highly variable
• They all induce almost similar liver cell damage
• Broad groups
• Infection-related hepatitis
• Non-infection-related hepatitis

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Hepatitis clinical spectrum

• Infection hepatitis
• Viral, bacterial, parasitic
• Non-infection hepatitis
• Alcoholic hepatitis
• Autoimmune hepatitis
• Drug induced hepatitis
• Toxic hepatitis
• Non-alcoholic-steatotic hepatitis (NASH)
• Non alcoholic fatty liver
• Miscellaneous causes of hepatitis

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Hepatitis due to infections

• Infections
• Viral
• Hepatitis viruses the liver is the primary
  target
• A, B, C, D, E
• Non hepatitis viruses the liver is secondarily
  infected
• HSV, EBV, CMV, yellow fever
• Bacterial
• Leptospira icterohemorrhagicae, coxiella
  burnetii, TB
• Parasitic
• Toxoplasma gondii
• Fungal
• Deep mycosis histoplasma capsulatum

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Non-infectious hepatitis

• Non-infectious causes of hepatitis
• Alcohol
• Drugs
• Paracetamol, methotrexate, methyldopa,
  ketoconazole
• Isoniazid, rifampicin, nitrofurantoin
• Toxins/poisons
• Amanita Phalloides (Mushrooms), Aflatoxin,
• Carbon tetrachloride, Herbal Medicine
• Non-Alcoholic Steato-Hepatitis
• (NASH)
• Circulatory insufficiency
• Congestive Heart Failure

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Hepatitis clinical classification

• Clinical types based on duration
• Acute hepatitis
• Hepatitis lasting less than 6 months
• Chronic hepatitis
• Hepatitis lasting for 6 months or longer

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Pathology Acute hepatitis

• In Acute hepatitis
• Histologic hepatocyte changes
• Almost similar regardless of etiology
• Degenerative changes
• SWELLING
• Cytoplasmic granularity, vacuolation
• NECROSIS
• Cell injury resulting in premature cell death
• By autolysis
• There is collapse and shrinkage of the liver
  parenchyma
• With formation of eosinophilic councilman bodies

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Pathology acute hepatitis ct

• Extent of liver damage
• Varies greatly between individuals
• Who have been affected by the same agent e.g.
  alcohol
• Massive hepatocyte necrosis leads to fulminant
  hepatitis
• Which leads to Liver failure
• Other changes
• Collapse of reticulin framework
• With bridging between central veins
• Cholestasis
• Blockage of bile flow
• Fatty degeneration
• Especially in alcoholic hepatitis (fatty
  alcoholic liver)

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Pathology Chronic hepatitis

• In chronic hepatitis
• Changes include
• Infiltration with chronic inflammatory cells
• Lymphocytes
• Plasma cells
• Extent of inflammation varies
• Mild to severe

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Chronic hepatitis ct.

• Other features
• Confluent necrosis (merging or propagatory
  necrosis)
• Fibrosis
• Fibrous tissue formation leads to Bridging across
  portal tracts,
• Eventually
• Disruption of the hepatic architecture with
  shrinkage
• Leads to Liver Cirrhosis

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Hepatic fibrosis

• Hepatic fibrosis
• There is overly exuberant wound healing in which
• Excessive connective tissue builds in the liver
• Extracellular matrix is
• overproduced,
• Deficiently degraded
• OR BOTH
• Fibrosis leads to scarring with
• Distortion of blood flow through the liver
  parenchyma
• Portal hypertension
• Disruption of normal hepatic architecture and
  function
• Liver cirrhosis

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VIRAL HEPATITIS

• Viral hepatitis could be due to
• Hepatitis viruses
• A, B, C, D, E,
• NON-A-E
• Cannot be typed
• Constitute 10 15 of hepatitides
• Do not cause disease in man they include
• GB agent
• HGV Hepatitis G Virus
• TTV Transfusion Transmitted Virus
• Non Hepatitis viruses (other viruses)
• HSV, EBV, CMV, YFV

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HEPATITIS A

• An infectious disease of the liver
• Caused by hepatitis A virus (HAV)
• A PICORNA VIRUS
• The most common viral hepatitis globally
• It has a World wide occurrence
• Occurs Especially in epidemics
• Common in
• Children
• Who are usually asymptomatic carriers
• Young adults

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Hepatitis A ct-

• Transmission
• Feco-oral route ingesting contaminated food
• Especially shellfish
• Crabs, Crustaceous
• Viral Replication takes place in the liver
• Excretion in BILE then FECES for 2 weeks before
  onset of illness and 7 days after

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Epidemiology Hepatitis A

• Globally annually
• 1.4 million symptomatic cases
• 114 million infections Symptomatic
  Asymptomatic
• It is more common in regions with
• Poor sanitation
• Inadequate safe water supply

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Epidemiology ct

• In the developing world
• About 90 of children have HAV infection by age
  10,
• Hence become immune by adulthood.
• It often occurs in outbreaks
• In moderately developed countries
• Where children are not exposed when young, and
• Vaccination is not widespread.
• Acute hepatitis A
• Resulted in 11,200 deaths in 2015

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Clinical features
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Clinical features

• Incubation period 2 6 weeks (short incubat)
• Presentation
• Symptomatic or asymptomatic
• Symptomatic
• During viremia non-specific features
• Unwell flu-like illness, malaise, fever, nausea,
  
• Anorexia, vomiting, diarrhea, abdominal pain
• After 1-2 weeks
• Some become jaundiced,
• Symptoms disappear with onset of jaundice

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• NB
• As jaundice deepens
• Urine becomes dark,
• Stools pale
• Due to intrahepatic cholestasis with intrahepatic
  pooling of bilirubin

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• Other features
• Transient skin rash viral exanthem
• Moderate hepatomegaly,
• Splenomegaly 10 of patients
• Tender lymphadenopthy occasional
• Symptoms usually last 3-8 weeks
• Acute liver failure Acute Fulminant Hepatitis
• May occur rarely
• Common in the elderly, may lead to
• Hepatic coma death

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Investigations

• Liver Biochemistry Liver Function Tests
• Serum bilirubin
• May be normal during un icteric phase (no
  jaundice phase)
• Rises proportionately during icteric phase
• Urine bilirubin
• Bilirubinuria
• Urinary urobilinogen
• Raised
• serum AST ALT
• Max levels 1-2 days after onset of jaundice
• May remain elevated for weeks to 6 months after
  jaundice

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Investigations ct-

• Hematological tests
• FBP
• Leucopenia with relative lymphocytosis
• Anemia (Coombs positive hemolytic anemia)
• Aplastic anemia
• Viral markers HAV antibodies (after 28 days)
• IgG marker of chronic infection very common
• Persists for life
• IgM marker of acute infection
• Disappears within 6 months

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Treatment

• No specific treatment
• Diet
• Bed rest
• Advised
• Corticosteroids ????
• No proven benefit
• Hospital admission
• Usually not necessary

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• Prognosis
• Usually excellent
• However, around 1015
• Will experience Recurrence WITHIN 6 MONTHS
• Mortality in young adults
• 0.5 May increase with age
• Death
• May be due to fulminant hepatitis

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• Prognosis ct
• Cholestatic viral hepatitis occasional there
  is
• Prolonged course of severe jaundice with
  cholestasis
• Up to 7-20 weeks
• Progress to chronic liver disease (CLD)???
• Does not occur
• Prevention
• Active immunization HAV vaccine single jab
  10yrs protection
• Passive immunization normal human immunoglobulin

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Extra-hepatic complications

• Rare, include
• Arthritis
• Vasculitis
• Myocarditis
• Renal failure

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HEPATITIS B

• Infection of the liver by hepatitis B virus
• It causes
• Acute HBV infection
• Chronic HBV infection
• Which is the Most feared
• May cause Chronic Liver Disease which includes
• Chronic hepatitis
• Liver cirrhosis
• Hepatocellular carcinoma
• Epidemiology
• Distribution world-wide
• Estimated 250-350 million chronic carriers

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Global seroprevalence of Hepatitis B WHO May
2016
Endemicity Prevalence Examples
High gt 8 West Africa
High intermediate 5 - 7 Sub Saharan Africa, SEA, Eastern Europe
Low intermediate 2 - 4 North Africa, Middle East, Australia,
Low lt 2 Western Europe, North America, Canada
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Modes of transmission
Mode Groups at risk Examples
Horizontal through skin to skin contacts Adolescents with broken skins in high and intermediate high prevalence (gt 80) Sub-Saharan Africa
Mother to Child at the time of parturition Babies born of infected mothers who are HBeAg positive India
Parenterally Recipients of unscreened BT, use of unsterile piercing instruments, tattooing Sub-Saharan Africa. Parts of Asia
Sexually Inhabitants of low prevalence areas Western Europe, North America, Canada (also through tattooing)
Trans-placental ?speculative (5)? ?? ??
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Pathogenesis HBV proteins
HBV protein Remarks
Core Replication?
Pre-core (HBeAg) Marker of active replication Role in inducing immunotolerance
Surface (HBsAg) Envelope protein Indicates infection
Pre-S1 Pre-s2 Binding and Entry into hepatocytes
Polymerase Viral replication
X protein Transcriptional and Transactivator activity
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HBV genome
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Pathogenesis HBV genome
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Pathogenesis

• Hepatitis B virus
• Penetrates by binding to hepatocyte
• Through pre S1 and pre S2 regions
• After penetration
• The virus loses protein coat
• The virus core gets incorporated into the
  hepatocyte genome
• Takes over control of host nuclear activity
• Preponderance to malignant transformation
• HBV is not directly cytopathic liver damage
• Result of host cellular immune response

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• Cell Mediated Immune responses
• Th1 response
• Interleukin 2,
• Interferon Gamma
• Responsible for clearance of virus
• Inhibits viral replication
• Th2 response
• Interleukin 4, 5, 6, 10, 13
• Associated with defective viral clearance
• Leads to chronic infection, severity of disease

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• Viral persistence in individuals with
• Poor C-MI response
• Leads to Chronic Inactive HBV Infective State
• No hepatocellular damage
• Previously referred to as Healthy Chronic
  Inactive Carriers
• Strong C-MI response
• Leads to Chronic Active HBV infection
• Continuing hepatocellular damage

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Clinical features
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Clinical features

• May be subclinical
• Features also determined by
• Age at infection
• Perinatal
• No clinical disease
• High level of immune-tolerance
• 90 chronic carrier rate
• State of immune competence
• Compromised individual
• Subclinical or mild disease
• Serotypes and genotypes
• Serotypes adr adw ayr ayw
• Genotypes A H

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Investigations

• Basically same as HAV
• FBP, Biochemistry (ALT)
• Sero-markers
• Antigens
• HbsAg
• HBeAg
• Antibodies
• Anti-HBs
• Anti-HBc
• Anti- HBe
• HBV DNA Viral load
• PCR

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Treatment

• Acute HBV
• Essentially asymptomatic
• Chronic HBV
• Treatment depends on
• Viral load HBV DNA load gt 20,000 IU/mL
• Evidence of liver disease as shown by
• Elevation of ALT gt 1 ½ x the upper limit of normal

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Treatment and prevention

• Treatment
• Antivirals
• Most commonly used
• Lamivudine, Adefovir, Tenofovir, Antecavir
• Interferons
• Interferon alpha 2a
• 180 µg sc per week
• Prevention
• Immunization
• Vaccination
• Immunoglobulin
• Health education

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HEPATITIS D

• Hepatitis D
• Caused by the hepatitis delta virus (HDV)
• A small spherical enveloped particle
• HDV is one of five known hepatitis viruses
• A, B, C, D, and E.
• It is considered to be a satellite
• A type of subviral agent
• Because it can propagate only
• In the presence of the hepatitis B virus (HBV)

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• Transmission of HDV
• Can occur either via
• Simultaneous infection with HBV
• Co-infection or
• Superimposed on chronic hepatitis B or hepatitis
  B carrier state
• Superinfection

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HD/B

• Both superinfection and coinfection with HDV
• Result in more severe complications
• Compared to infection with HBV alone
• Complications include
• Greater likelihood of liver failure in acute
  infections
• Rapid progression to liver cirrhosis
• Increased risk of developing liver cancer in
  chronic infections
• In combination with hepatitis B virus
• HDV has the highest fatality of all the hepatitis
  infections
• About 20.

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HDV epidemiology

• Worldwide
• HDV was discovered in 1977
• More than 15 million people are co-infected
• HDV is rare in most developed countries
• Where it is mostly associated with IVDU
• HDV is much more common in
• Mediterranean region
• Sub-Saharan Africa
• Middle East
• South America
• Northern part

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Treatment and Prevention

• Treatment
• Conventional or pegylated
• Interferon alpha therapy
• Prevention
• The HBV vaccine
• Protects against hepatitis D virus
• Because of the dependence on HBV for replication
• In absence of a specific vaccine against HDV
• The HBV vaccine must be given
• Soon after birth in risk groups

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HEPATITIS C

• Acute HCV infection is often considered
• Chronic infection
• The virus persists in the liver
• In about
• 75 to 85 of those initially infected
• Frequency 58 mil (2019)
• Death 290 000 (2019)

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Hepatitis E

• Frequency 28 mil (2013)
• Symptoms nausea, jaundice
• Differential HAV

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End End End