المرحلة الرابعة
باطنيةالعدد2
15\2\2018AUTOIMMUNE HEPATITIS
الدكتور خلدون ذنون- كلية طب نينوىالمرحله الرابعة
Objectives
Hepatitis can be caused by an autoimmune process.
It is a chronic process, but may present acutely.
Diagnosis is established by liver biopsy and serology.
Immunosuppressive therapy is used to control the disease.
Most patients develop cirrhosis.
Subtypes
Classical type1 AH: associated with autoimmune disorders e.g Graves disease, HLA-DR3, HLA-DR4; high titres of antinuclear& anti-smooth muscle antibody.Type11 AH: associated with liver-kidney microsomal antibody (LKM); lacks ANA& anti-SMA.
Type 111: increased serum immunoglogulins with antibodies against soluble liver antigens.
Pathology
Inflammatory cells invade peripheral parenchyma with loss of definition of the portal-periportal interface (limiting plate).
Damage to the peripheral hepatocytes & formation of hepatocye rosettes termed interface hepatitis previously termed chronic active hepatitis.
Progressive parenchymal damage & fibrosis leading to cirrhosis.
Clinical features
It is a chronic hepatitis, mostly affects females in the 2nd & 3rd decade of life.Insidious onset of fatigue, anorexia & jaundice. In 25% the onset is acute.
Fever, arthralgia, vetiligo, epistaxis & amenorrhea.
Jaundice: mild, moderate or absent.
Hepatosplenomegaly & spider telangiectasia.
Sometimes cushingoid face: acne, hirsutism, bruises & pink cutaneous striae on thighs & abdomen.
Associated with: migrating polyarithritis, urticaria, LAP, Hashimotos thyroiditis, thyrotoxicosis, myxoedema, coombs +ve haemolytic anaemia, pleurisy, pulmonary infiltrates, ulcerative colitis, glomerulonephritis & nephrotic syndrome.
Investigations
( ( Aminotransferase activity may be >10 folds( ( ALP due to intrahepatic cholestasis.
( Jaundice: usually not more than 100mol/L 6mg/dl.
( ( Albumin & ( PT due to liver damage.
( Polyclonal hyperglobulinaemia: ( IgG mainly.
( Type1: ANA in 80%, anti-SMA in 70% both in high titre.
( Type11: anti LKM +VE.
( The antibodies are nonspecific, may be present in normal people,
other autoimmune diseases, infectious mononucleosis & malignant
diseases.
( Liver biopsy: is mandatory and shows interface hepatitis.
Management
Corticosteroids are life-saving; oral prednisolone 30mg/day reduced gradually overtime as liver function tests improve.When LVT becomes normal maintain steroid for at least 2 years.
Withdraw steroid when liver biopsy becomes normal.
Azathioprine 50-100mg/day orally may be added to allow reduction of prednisolone dose to 10mg or less.
Corticosteroids treat & prevent acute exacerbations rather than prevent cirrhosis; less important for mild disease.
Prognosis
Course: exacerbations & remissions.Most patients develop cirrhosis.
50% of symptomatic patients die of liver failure within 5 year if no treatment is given, with therapy it falls to 10% .
ALCOHOLIC LIVER DISEASE
ObjectivesAlcohol ingestion can cause all range of liver disease.
The only step which stop or reverse liver damage is by abstinence from alcohol ingestion.
Pathogenesis
Alcohol is metabolised in the liver. Alcohol dehydrogenase converts alcohol into acetaldehyde which is converted into acetate by the action of acetaldehyde dehydrogenase; acetate is metabolised by the Krebs cycle.
Alcohol induces cytochrome p450 E1, which increases the metabolism of alcohol, drugs, toxins or carcinogens.
Alcoholic liver disease is related directly to the amount & duration of alcohol consumption.
It is clinically apparent at daily intakes above 30 gm (3 units) in men & 20 gm (2 units) in women.
5-10 years are needed to produce alcoholic cirrhosis.
Liver damage is related to: toxic alcohol metabolites, altered liver cell immune reaction, inflammatory cells, release of cytokines e.g TNF- (, IL-1 & IL8, nutrition, genetic factors, coexistent disorders e.g viral hepatitis & haemochromatosis.
Pathological features
Mitochondrial swelling ( proliferation of endoplasmicreticulum
Macrovascular steatosis ( lipogranuloma ( Mallorys hyaline
Siderosis ( Autoimmune (interface) hepatitis
central hyaline sclerosis ( Fibrosis ( Cirrhosis
Hepatocellular carcinoma
Clinical features
Range from non-specific symptoms, with few or no physical abnormalities, to advanced cirrhosis.Hepatomegaly due to fatty liver which is non-specific.
Cholestasis: jaundice, abdominal pain, tender hepatomegaly.
Hepatitis: severe illness, malnutrition, jaundice, hepatomegaly, ascites, encephalopathy.
Cirrhosis: stigmata of cirrhosis, varices, ascites, encephalopathy, hepatorenal syndrome, hepatocellular cancer.
Investigations
Establish alcohol misuse: clinical history from the patient, relatives & friends.
Indicators of alcohol misuse: peripheral blood macrocytosis in the absence of anaemia & ( plasma (GT , rib fractures .
LVT are needed which depend on extent of liver damage.
Liver biopsy: may show steatosis (fat globules within the cytoplasm of liver cells), hepatitis, fibrosis & cirrhosis.
Management
Cessation of alcohol intake is the most important treatment.Good nutrition, nasogastric tube feeding in severely ill patients.
Treatment of complications: bleeding, ascites & encephalopathy.
Corticosteroids and pentoxifylline may be used in severe alcoholic
hepatitis.
Continuous psychiatric services.
Liver transplant: is indicated in advanced liver disease in those who abstain from alcohol, with the help of psychiatrist, aiming to separate those with harmful alcohol intake from those with alcohol misuse.
Prognosis
The most important prognostic factor is the patients ability to stop drinking alcohol.Alcoholic fatty liver: good prognosis, disappears after 3 months of abstinence.
Alcoholic hepatitis: worse prognosis, one 1/3 die during hepatic encephalopathy & ( PT.
Alcoholic cirrhosis: serious complication, 1/2 survive 5 years, survival is increased when they stop drinking.