CHRONIC HEPATITIS

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CHRONIC HEPATITIS
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The contours of the liver and spleen as wellas
the gall bladder in the right and left
hypochondrium
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THE ANATOMY OF THE PORTAL VENOUS SYSTEM
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CHRONIC HEPATITIS
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CHRONIC HEPATITISDefinition

• Chronic hepatitis is a broad clinical and
  pathologic syndrome that encompasses an
  etiologically diverse group of diseases
  characterized by long-term elevation of liver
  chemistries and the finding of hepatic
  inflammation on liver biopsy.
• Chronic hepatitis is generally defined as disease
  that has lasted for 6 months or longer

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• Anxiety
• Arthritis
• Ascites (swelling in the stomach area)
• Blurred Vision
• Chills
• Dark Urine
• Decline in sex drive
• Depression
• Dizziness
• Dry Skin
• Edema (swelling of the hands, feet legs)
• Excessive Bleeding
• Excessive gas
• Eye or eyesight problems (blurred vision or dry
  eyes)
• Fatigue
• Fever
• Flu-like symptoms
• Gallstones
• Gray, yellow, white or light colored stools

• Inflammation in the joints
• Insomnia
• Irritability
• Itching
• Jaundice (yellowing of eyes and/or skin)
• Joint pain
• Mood changes or swings
• Memory loss, mental confusion
• Menstrual problems
• Muscle aches
• Nausea
• Rashes/Red spots
• Red palms
• Sensitivity to heat or cold
• Sleep disturbances
• Slow healing and recovery
• Susceptibility to illness/flu
• Sweating
• Vertigo

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CYTOLYTIC SYNDROME

• alanine aminotransferase increased,
• aspartate aminotransferase increased
• Increased LDH
• Increased ferritin
• Hyperbilirubiemia

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Cholestasis

• Alkaline phosphatase
• elevations of serum bile acid levels
• elevated levels of Gamma Glutamyl Transferase
  GGT
• itchiness (pruritus). Pruritus is the primary
  symptom of cholestasis
• jaundice.
• pale stool. This symptom implies obstructive
  cholestasis.
• dark urine
• Bile is secreted by the liver to aid in the
  digestion of fats. Drugs such as gold salts,
  nitrofurantoin, anabolic steroids,
  chlorpromazine, prochlorperazine, sulindac,
  cimetidine, erythromycin, estrogen can cause
  cholestasis and may result in damage to the liver.

• abdominal mass (e.g. cancer)
• biliary atresia and other pediatric liver
  diseases
• biliary trauma
• congenital anomalies of the biliary tract
• gallstones
• intrahepatic cholestasis of pregnancy (obstetric
  cholestasis)
• primary biliary cirrhosis, an autoimmune disorder
• primary sclerosing cholangitis, associated with
  inflammatory bowel disease
• some drugs, (e.g. flucloxacillin and
  erythromycin)
• ABCC2 gene polymorphism

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hepatocellular insufficiency

• Albumin
• Transferrine
• Chplesterol
• protro,mbine
• Cholinesterasa
• ?-lipoproteins
• Hyperbilirubinemia

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Mesenchymal inflammation

• Hyper-? globulinemia
• CRP
• ESR

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CHRONIC HEPATITIS CLASSIFICATION

• Chronic Viral Hepatitis B
• Chronic Viral Hepatitis C
• Chronic Viral Hepatitis D
• Chronic Viral Hepatitis nonidentificated
• Autoimmune Hepatitis (type 1, 2 ,3)
• Toxic Hepatitis, Drug-Induced Hepatitis
• Cryptogenic Hepatitis
• Alcoholic Hepatitis
• Metabolic Hepatitis
• Cholestatic Hepatitis
• Nonspecific Reactive Hepatitis

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Grades of Inflammationand Stages of Fibrosis on
Liver Biopsies
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CHRONIC HEPATITIS CLASSIFICATION ACCORDING TO
SEVERITY (level of Aminotransferases)
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CHRONIC HEPATITISCOMPLICATIONS

• HEPATIC ENCEPHALOPATHY
• VARICEAL BLEEDING
• ASCITES
• GLOMERULONEPHRITIS
• OTHERS

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CHRONIC HEPATITIS CLASSIFICATION

• CHRONIC VIRAL HEPATITIS B
• CHRONIC VIRAL HEPATITIS C
• CHRONIC VIRAL HEPATITIS D
• CHRONIC VIRAL HEPATITIS NONIDENTIFICATED
• Autoimmune Hepatitis (type 1, 2 ,3)
• Toxic Hepatitis, Drug-Induced Hepatitis
• Cryptogenic Hepatitis
• Alcoholic Hepatitis
• Metabolic Hepatitis
• Cholestatic Hepatitis
• Nonspecific Reactive Hepatitis

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General Concepts

• Hepatitis 'inflammation of the liver'.
• six medically important viruses are commonly
  described as hepatitis viruses
• HAV,HBV,HCV,HDV,HEV,HGV.

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Viral Hepatitis - Historical Perspectives
Enterically transmitted
Infectious
A
E
Viral hepatitis
NANB
Parenterally transmitted
B
D
C
Serum
F, G, TTV ? other
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Table 24.12
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CHRONIC VIRAL HEPATITIS

• 5 to 10 of cases of hepatitis ? (with or without
  hepatitis D virus co-infection)
• and about 75 of cases of hepatitis C become
  chronic.
• Infection with hepatitis A virus or hepatitis E
  virus is not a cause of Chronic Hepatitis.

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HBV Structure
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HBV Structure Antigens
Dane particle
HBsAg surface (coat) protein ( 4 phenotypes
adw, adr, ayw and ayr) HBcAg inner core protein
(a single serotype) HBeAg secreted protein
function unknown
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Possible Outcomes of HBV Infection
Acute hepatitis B infection
3-5 of adult-acquired infections
95 of infant-acquired infections
Chronic HBV infection
Chronic hepatitis
12-25 in 5 years
Cirrhosis
20-23 in 5 years
6-15 in 5 years
Hepatocellular carcinoma
Liver failure
Liver transplant
Death
Death
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7?Laboratory Diagnosis
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CHRONIC VIRAL HEPATITIS

• Hepatitis B virus and hepatitis C virus are the
  major causes of chronic hepatitis in the world.
• Approximately 80 of individuals infected with
  HCV will become chronic carriers, of whom a
  majority will develop a degree of liver damage
  ranging from fatty liver to cirrhosis.
• Chronic HBV and HCV infection predispose patients
  to developing hepatocellular carcinoma.

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CHRONIC HEPATITIS CLASSIFICATION

• Chronic Viral Hepatitis B
• Chronic Viral Hepatitis C
• Chronic Viral Hepatitis D
• Chronic Viral Hepatitis nonidentificated
• AUTOIMMUNE HEPATITIS (TYPE 1, 2 ,3)
• Toxic Hepatitis, Drug-Induced Hepatitis
• Cryptogenic Hepatitis
• Alcoholic Hepatitis
• Metabolic Hepatitis Cholestatic Hepatitis
• Nonspecific Reactive Hepatitis

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AUTOIMMUNE HEPATITIS

• Autoimmune hepatitis is four times more common in
  women than in men,
• and is most aggressive when it presents in the
  third and fourth decades.
• AIH can be associated with other autoimmune
  diseases.
• Important differential diagnoses include viral
  hepatitis, Wilson's disease and drug reactions.
• There is a rise in IgG, a positive
  anti-smooth-muscle antibody present in 60, and
  antinuclear antibody and liver-kidney microsomal
  antibody (LKM-1) may be present.
• Long-term immunosuppression is required with
  corticosteroids and often azathioprine. Response
  rate to therapy (corticosteroids) is 80-90.

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AUTOIMMUNE HEPATITIS

• Patients with severe disease who are
• treated with corticosteroids have a 10-year
• survival rate of 60 to 70,
• whereas untreated patients have a survival rate
  of less than 30.

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CHRONIC HEPATITIS CLASSIFICATION

• Chronic Viral Hepatitis B
• Chronic Viral Hepatitis C
• Chronic Viral Hepatitis D
• Chronic Viral Hepatitis nonidentificated
• Autoimmune Hepatitis (type 1, 2 ,3)
• TOXIC HEPATITIS, DRUG-INDUCED HEPATITIS
• Cryptogenic Hepatitis
• Alcoholic Hepatitis
• Metabolic Hepatitis
• Cholestatic Hepatitis
• Nonspecific Reactive Hepatitis

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DRUG-INDUCED CHRONIC HEPATITIS

• Hepatotoxic drugs
• - Paracetamol
• - Isoniazid
• - Oestrogens
• - Antibiotics
• -Methotrexate
• -others

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FATTY LIVER

• Fat droplets appear in the cytoplasm of
  hepatocytes
• they may appear a few days after an alcohol
  binge, but are almost always present in heavy
  drinkers (gt 80 g of alcohol per day for gt 5
  years).
• Fatty liver may occur, however, with obesity,
  diabetes mellitus, starvation and chronic
  hepatitis C virus infection

Fatty Liver
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ALCOHOLIC HEPATITIS

• Alcohol abuse is a massive international problem
  which has huge resource implications both for the
  community as a whole and also for health care.
• Alcohol is enjoyed by many and used safely by the
  majority of people who drink it.
• Alcohol abuse may be denied or not recognized by
  individuals or their families and friends.
• Alcohol damages not only the liver, but many
  other organs also.

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Effects of alcohol abuse
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ALCOHOLIC HEPATITIS

• Alcoholic liver disease may develop in women
  after less alcohol consumption than is necessary
  to cause hepatitis or cirrhosis in men.
• Daily alcohol consumption of approximately 50 g
  for 10 to 15 years is associated with alcoholic
  liver disease in women, whereas 80 g is
  associated with alcoholic cirrhosis in men.

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ALCOHOLIC HEPATITIS

• Alcoholic hepatitis refers to the pathologic
  Mallory stain findings of alcoholic hyalin
  surrounded by polymorphonuclear cell inflammation

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METABOLIC HEPATITIS

• HEMOCHROMATOSIS Characterized by excessive
  deposition of iron in liver
• WILSON DISEASE Characterized by excessive
  deposition of copper in liver (mostly in young
  patients)
• a1-ANTITRYPSIN DEFICIENCY results in cirrhosis
  and emphysema

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CHRONIC HEPATITISDIAGNOSIS

• LABORATORY SYNDROMES
• Cytolitic syndrome (?AST, ?ALT, ?GGT,
  ?Bilirubin )
• Cholestatic syndrome (?conjugated Bilirubin,
  ?Alkaline phosphatase, ?GGT, ?cholesterol)
• Liver cellular insufficiency syndrome (?Albumine,
  ?prothrombin, ?cholesterol, ?fibrinogen)
• Mesenchyme-inflammatory syndrome (?ESR,
• ??-globulins, ?timol test ?Le, ?C-react.
  protein)
• Hypersplenism (anemia, thrombocytopenia,
  leukocytopenia)

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CHRONIC HEPATITISPLAN of INVESTIGATIONS

• Total blood count
• Biochemical analysis (Glucose, Bilirubin, ALT,
  AST, GGT, Alkaline phosphatase, Albumin,
  ?-globulins, Cholesterol, Liver tests, Sodium,
  Potassium, Urea, Creatinine)
• Urinanalysis, Diastase of urine
• Coagulogram
• Markers of Viral Hepatitis (chain polimerase
  reaction, immunoenzyme analysis)
• Immunogram
• Coprogram
• ECG
• Endoscopy
• USD, CT
• Needle liver biopsy

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CHRONIC VIRAL HEPATITIS TREATMENT

• ANTIVIRAL THERAPY (Interferon therapy, Lamivudine
  therapy)
• Corticosteroids are contraindicated, because
  viral replication is enhanced

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INTERFERON THERAPYSide effects

• influenzalike symptoms (fever, myalgia,
  arthralgia, and headache),
• hematologic toxicity (granulocytopenia,
  leukopenia, and thrombocytopenia),
• systemic symptoms (fatigue and hair loss),
• neurologic signs (decreased concentration,
  depression, and irritability),
• immune system disorders (development of
  autoantibodies, thyroid disease, or other
  autoimmune diseases)

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CONTRAINDICATIONS TO INTERFERON THERAPY

• hypersensitivity to interferon
• decompensated cirrhosis
• immunosuppression associated with organ
  transplantation
• active autoimmune disease
• significant psychiatric disease, including
  depression
• pregnancy

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Autoimmune Hepatitis
Week Monotherapy Prednisolone, mg Prednisolone (mg) and Azathioprine (mg/kg) combination therapy Prednisolone Azathioprine Prednisolone (mg) and Azathioprine (mg/kg) combination therapy Prednisolone Azathioprine
1 50 50 50-150
2 50 40 50-150
3 40 30 50-150
4 30 20 50-150
5 25 15 50-150
6 20 12,5 50-150
7,8 15 10 50-150
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HEPATOPROTECTORS
Plant Carsil, Legalon, Hepabene, Chofitol
Essential phospholipids Essentiale, Enerliv
Aminoacids Glutargin, Citrarginin
a- lipoic acid Berlithion
Ursodezoxycholic acid Ursofalc, Ursosan
Synthetic Thiotriazolin, Antral
Animal Vitohepat, Sirepar
Homeopathic Halstena
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Thank you for attention!