Hepatitis
By Dr. Mohammed E. Salem
Lecturer of internal medicine
Classification
Acute Chronic
hepatitis hepatitis
Acute hepatitis
Definition
Diffuse liver inflammation lasting < 6 months.
Etiology
• Infection:
o Hepatotropic viruses: mainly hepatitis A, B, C, D, E viruses
o Non hepatotropic viruses: less commonly: CMV, EBV, HSV, yellow fever viruses.
• Immunological:
o Autoimmune hepatitis.
• latrogenic: drug induced liver injury :
o Paracetamol: >10 gm (> 15 gm causing fulmininat hepatic failure).
o Alcohol
o Anesthetic: Halothane
o Isoniazid
o Phosphorus, Carbon tetrachloride
o DDT (Dichloro-diphenyltrichloroethane)
Etiology
• Ischemic:
o Acute Budd-chiari syndrome
o Shock
• Congestive:
o Heart failure (congestive hepatopathy).
• Metabolic:
o Wilson disease
o Acute fatty liver of pregnancy
o Reye's syndrome
Viral hepatitis
• Nature:
o HAV, HCV, HDV, HEV: RNA
o HBV: DNA
• Mode of transmission:
o HAV, HEV: feco-oral
o HCV, HDV: parenteral, sexual
o HBV: parenteral, sexual, vertical (transplacental)
Clinical picture
1. Anicteric hepatitis:
• Patient presents with influenza-like picture with enlarged tender liver
Clinical picture
2. Icteric hepatitis:
1- Pre-icteric stage: 1-2 weeks
• Fever, headache, malaise
• Anorexia (particularly to
cigarettes), nausea and
vomiting
• Pain in the right
hypochondrium &
epigastrium
• Enlarged tender liver
Clinical picture
2. Icteric hepatitis:
2- Icteric stage: 2-4 weeks
• Temperature drops to normal
• Anorexia markedly improves
• Jaundice with dark urine & pale stool with steatorrhea
• Enlarged tender liver.
• Splenomegaly (20% of cases)
• Generalized lymphadenopathy (10 % of cases)
Clinical picture
2. Icteric hepatitis:
3- Convalescence stage: 6 months.
• Gradual improvement in all symptoms and signs.
• The liver returns to normal within 6 months.
• Complete recovery occurs in most cases of HAV & HEV.
Sequelae and complications
1. Complete recovery
2. Relapses
3. Chronic Sequelae:
• Carrier
• Chronic hepatitis
• Cirrhosis: post-hepatic cirrhosis
• Carcinoma: hepatocellular carcinoma
Sequelae and complications
4. Fulminant hepatitis: Severe acute liver cell failure with encephalopathy &
coagulopathy
5. Post hepatitis cholestasis: Persistence of jaundice & pruritus up to 6
months, followed by complete recovery
6. Post hepatitis syndrome: The liver functions are normal except for mild rise
of liver enzymes
Sequelae and complications
7. Extra-hepatic complications :
• Aplastic anemia
• Arthritis
• Glomerulonephritis (only with HBV & HCV)
• Cryoglobulinemia (only with HBV & HCV)
• Polyarteritis nodosa (only with HBV & HCV)
• Sjogren's syndrome
• Guillain-Barre syndrome
• Porphyria cutanea tarda & Lichen planus
Investigations
• Liver function tests:
o AST & ALT: marked ↑
o Bilirubin: ↑ total, both direct & indirect bilirubin
o Prothrombin time: ↑
o Albumin: normal
• Blood picture:
o Leucopenia with relative lymphocytosis
• Imaging: Ultrasound
o Hepatomegaly and possible splenomegaly
Investigations
• Hepatitis markers:
o Hepatitis A: HAV Ab IgM & IgG
o Hepatitis E: HEV Ab IgM & IgG
o Hepatitis D: HDV Ab IgM & IgG ; and PCR for RNA
o Hepatitis C: HCV Ab; and PCR for RNA
o Hepatitis B:
▪ Antigen: HBsAg, HBcAg (only in liver biopsy), HBeAg
▪ Antibody: HBsAb, HBcAb IgM & IgG, HBeAb
▪ PCR for DNA
Investigations
• HBV structure:
Investigations
N.B. Window Gap:
• It is a window period lasting several
weeks from disappearance of HBsAg
to appearance of HbsAb (Both are
negative).
• During this gap period, HBcAb IgM is
always positive and diagnostic of
recent HBV infection.
Prevention
• HAV
1- Pre-exposure -prophylaxis:
❑ HAV vaccine:
o Indication: travelers to endemic areas
o Value: protection 100 % for more than 10 years
❑ Immunoglobulin:
o Indication: allergy to vaccine component
2- Post-exposure prophylaxis:
❑ Immunoglobulin:
o Indication: Within 2 weeks from the exposure of the unvaccinated individual
Prevention
• HBV
1- Pre-exposure -prophylaxis:
❑ HBV vaccine:
o Indication: for high-risk individuals including:
▪ Hemophiliacs and hemolytic anemia patients
▪ Hemodialysis patients
▪ Health care professionals
▪ Homosexuals & IV drug addicts
▪ Babies born to HBsAg-positive mothers
▪ Many countries has HBV vaccination in their infant or adult immunization programs
Prevention
2- Post-exposure -prophylaxis:
❑ Immunoglobulin:
o Indication:
▪ children born from HBV positive mothers, needle stick injury
o Precautions:
▪ The HBIG should be given within 48 hrs from exposure
▪ The HBV vaccine first dose should be given at different site of the body.
Treatment: Supportive
1. Bed rest
2. Diet:
o Avoid alcohol completely
o Carbohydrates is given freely
o Protein is given freely unless there is manifestations of liver cell failure
o Fat: avoided if the patient is nauseous because they are nauseating.
Treatment: Supportive
3. Symptomatic treatment:
o Nausea: metoclopramide
o Pruritus: Cholestyramine
4. Treatment of complications e.g. corticosteroids in cholestatic hepatitis .
Chronic hepatitis
Definition
Diffuse liver inflammation without improvement lasting > 6 months.
Etiology
• Infection:
o HBV, HCV & HDV infection.
• Immunological:
o Autoimmune hepatitis.
• latrogenic: drug induced liver injury:
o Alcohol
o Isoniazid
o Alpha-methyl dopa
o Nitrofurantoin
Etiology
• Metabolic:
o Nonalcoholic steatohepatitis (NASH)
o Wilson disease
o Hemochromatosis
o Alpha one antitrypsin deficiency
• Cryptogenic (unknown cause).
Classifications : according to
histopathology:
1. Chronic persistent hepatitis:
2. Chronic lobular hepatitis:
3. Chronic active hepatitis:
A. Mild form.
B. Severe Form.
Clinical picture (picture of the cause)
A. Of chronic viral hepatitis:
• Asymptomatic (Accidental discovered)
• Constitutional symptoms : low grade fever, fatigue, headache, anorexia & malaise
• Abdominal examination:
o In early cases there are hepatosplenomegaly
o In late cases there are shrunken liver & splenomegaly
• Chronic infection can lead to liver CIRRHOSIS with liver cell failure & portal
hypertension → hepatocellular carcinoma in late cases
• EXTRA-HEPATIC COMPLICATIONS are present in small number of cases.
Clinical picture (picture of the cause)
B. Of autoimmune hepatitis:
• More common in young aged females
• Associated with auto-immune & extra-hepatic manifestations e.g.:
o Autoimmune hemolytic anemia & immune thrombocytopenic purpura.
o Rheumatoid arthritis & systemic lupus erythematosus
o Celiac disease & ulcerative colitis
o Diabetes, autoimmune Thyroiditis & Graves disease
o Amenorrhea
o Fibrosing alveolitis.
Investigations
A. Of chronic viral hepatitis:
• Liver function tests:
o AST & ALT: mild ↑
o Bilirubin: ↑ total, both direct & indirect bilirubin
o Prothrombin time: ↑
o Albumin: ↓
• Detection of viral marker:
o HCV antibodies & HCV RNA.
o HBsAg, HBeAg & HBV DNA.
Investigations
• Abdominal ultrasonography:
o In early eases there are hepatomegaly & may be splenomegaly.
o In late cases there are shrunken liver (cirrhosis) & splenomegaly
• Assessment of degree of fibrosis:
A. Non invasive :
O Fibrosis markers.
O Fibroscan.
B. Invasive
O Liver biopsy.
Investigations
B. Of autoimmune hepatitis:
• Liver function tests: as chronic viral hepatitis
• Serology :
o High IgG leveL
o Type I:
▪ ANA : Anti-nuclear antibodies
▪ ASMA : Anti-smooth muscle antibodies
▪ Anti-SLA : Anti-soluble liver antigen
o Type II:
▪ Anti-LKM-1 & 3: Anti-liver kidney microsomal antibodies type 1 & 3
▪ Anti-LC-1: Anti liver cytosol antibodies type 1
• Liver biopsy
Treatment
A. Of chronic viral hepatitis:
• HBV
o Subcutaneous Interferon.
o Oral antiviral treatment: e.g. Entecavir, Lamivudine
• HCV
o Oral direct acting antiviral drugs (DAAs): e.g. sofosbuvir, daclatasvir
B. Of autoimmune hepatitis:
• Corticosteroids
• Immunosuppressive: e.g. azathioprine.
Thank you
