Non Alcoholic Liver Diseases

Common Features (autoimmune hepatitis)

• Associated with the presence of auto-antibodies (against self antigens)

• Usually increased serum IgG +/- IgM
• May be associated with AI diseases at other sites – thyroid, adrenal,

• Typical inflammatory cells– lymphocytes, plasma cells +/- lymphoid aggregates

• General: immune mediated liver damage
• May respond to immune suppression

Histological Features

1. Interface hepatitis: hallmark feature
   1. (piecemeal necrosis) is a process of inflammation and erosion of the hepatic parenchyma at its junction with portal tracts or fibrous septa.
2. Lobular inflammation, spotty necrosis
   1. +/- fibrosis/cirrhosis
3. No biopsy features which are specific but interface hepatitis must be present
4. Autoantibodies: useful disease markers

Antimitochondrial antibodies (AMA)

• Present in >95% cases.

Target tissue small bile ducts in liver

• Progressive bile duct damage-fibrosis
• Cirrhosis develops quite late

• Biochem- raised Alk Phophatase ++, bilirubin

• Raised Ig especially IgM (acute type)

• Symptoms: jaundice, pruritis (bile salts)

Histological Features

1. Portal tract inflammation
   1. lymphocytes;
   2. plasma cells +/- granulomas.
2. Hallmark- destruction of:
   1. small (40-80um) bile ducts,
   2. swelling in bile ducts may be focal hence need good Bx
   3. inflammation,
3. Late stage-fibrosis-micronodular cirrhosis

• intermittent areas of fibrosis and narrowing along bile duct

Eventual replacement of bile ducts with cord of fibrous tissue

• Affects intra and extrahepatic bile ducts

• Associated with IBD especially UC

• M>F 2-3:1

Symptoms and Signs

• Cholangitis (inflammation of bile duct)
  • recurrent inflammation due to obstruction
• Cholestasis (decrease in bile flow) due to obstruction
  • Presents: jaundice
• Fatigue, upper abdominal pain,intermittent/progressive jaundice
• Usually <50 years at presentation, can present in adolescence

Serology

Radiology

Histology

in >80% of cases (not specific)

– narrowing along bile duct

Early histological changes very non-specific

Alpha-1 antitrypsin is a protective enzyme that is produced in the liver, secreted into the bloodstream from the liver cells, and then carried through the blood to the lungs to help fight inflammation.

When there is not enough AAT in the lung, the body is no longer protected from the tissue breakdown effects of an enzyme in the white blood cells. When the white blood cells go to the lung (for instance, in conditions of lung inflammation like smoking or dusty environments), they release these enzymes into the lung. This can cause a breakdown in the walls of the air sacs (alveoli).

• Abnormality on chromosome 14-protease inhibitor Pi
• 75 different alleles, Z and M alleles associated with liver disease
  • Commonest PiZZ or PiMZ

• Presents in childhood
  • liver enzyme abnormalities,
  • cholestasis
• Associated with lung disease

Symptoms and Signs

• Jaundice (cholestasis – block)
• Vomiting
• Swelling or pain in your belly

• Poor growth
• Diarrhea
• Itching

• Poor appetite
• Swollen abdomen
• Fatigue

Blood Test

Chromosomal Test

Liver biopsy

Serum levels 30-40% of normal suggests the disease

of : PiZZ or PiMZ

abnormal accumulation of protein in cytoplasm

– pink with PAS-d stain or

– shown to be A1-AT on special stains.

+/- inflammation in liver

• Mutation of long arm of chromosome 13
• Defective gene involved in copper transport protein: excess copper

• Usually presents adolescents +/- adults
• Diagnosis considered in any patient >5 years with undiagnosed hepatocellular disease.

Blood Test

Examination

Histology

< 20mg/dl – 95%

of patients

(not diagnostic)

Biopsy:

Diagnostic: increased liver copper concentration

Liver

(Rhodanine, Orcein) Stains : copper

+ inflammation

• Autosomal recessive: chromosome 6
• Most common C282Y gene- homozygotes
• M>F, 10% gene carried NE Europe Celts

• Presents 40-60 yrs (M), later in women

Pathology: deposition of iron in liver, pancreas, testes

Symptoms and Signs

– weight loss.

– joint pain, usually in the joints of the second and middle fingers.

– Liver dysfunction.

– Sexual dysfunctions, such as impotence and low sex drive.

– disorders of the menstrual period, such as early menopause.

Blood Test

Chromosomal Test

Liver biopsy

Blood Withdrawal

Surgery

– venesection (therapeutic phlebotomy)

• RNA virus, spread fecal-oral- person to person contact or contaminated water
• Sporadic or endemic outbreaks
• Decreased incidence with increased hygiene in countries

• Mild hepatitis: many are sub-clinical
• Rarely associated with fulminant hepatitis

Histology:

very florid inflammation, spotty necrosis,

interface hepatitis, cholestasis

Well understood oncogenic virus

• > 350 million people infected in world

Most Common: China, SE Asia, Subsaharan Africa up to 15% of population infected

Distribution of HBV geographically associated with distribution of HCV

Central core and surface envelope

Surface antigen HBsAg:

first indication of the infection: 4-28 weeks (average 8 weeks) post infection.

Followed by appearance of HBeAg.

HBsAg is the hallmark of active current HBV infection whether acute or chronic.

Chronic HBV may have HBeAg present

Pathology

• picture of acute hepatitis, inflamm ++ apoptosis, spotty necrosis

Chronic HBV

• interface hepatitis, spotty necrosis, ‘ground glass’ hepatocyte
• glassy eosinophilic cytoplasm (contains ++ sAg in RER),
• Sanded nuclei’- nuclear inclusions (cAg)

Treatment:

• Lamividine (not curable)

Prevention: vaccination ‘at-risk’ groups

• First described 1989 –molecular cloning
• Responsible-most non-A non B hepatitis
• > 170 million carriers worldwide(3% pop)

• Small 30-38nm RNA virus, Flaviviridae
• Significant variation in viral genome- sub grouped to 11 genotypes

• Vary in geographical distribution

• Prior to 1990’s high incidence of infection was transfusion related

1990’s Ireland – single source outbreak from contaminated anti-D Ig given in 1970’s resulting in over 1000 women with past /current infection

Immunoglobulin Test

Polymerase Chain Reaction (PCR)

Antibodies identified in serum (ELISA and RIBA tests)

• viral RNA in serum (PCR)

Quantitative measurement PCR of viral load

(fibrosis)

Primary Sclerosing Cholangitis

• dilation

• Hepatocyte

– Integrate DNA into hepatocytes

– Codes for protein:

Disrupts growth control