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DEFINITION
          Viral Hepatitis

Inflammation of Liver caused
by viral infection.
VIRUSES

 Hepatotropic viruses
  (Five types of Hepatitis Virus have been identified).

   HAV, HBV, HCV, HDV, HEV

Others:
     HGV: Hepatitis G Virus

    TTV: Transfusion Transmitted Virus

    CMV: Cytomegalovirus

    EBV: Epstein-Barr Virus
Hepatitis A virus (HAV)

 Picornavirus single- stranded RNA genome,

 Single serological type: Anti-HAV-IgM and
  Anti-HAV-IgG

 Single antigen-antibody system

 Replication - cytoplasm of liver cells.
Epidemiology
 Most common Viral Hepatitis
 Source of Infection: patients.
 Route of spread : Faeco-oral
 Patient remains infectious 2 weeks prior
  to & for upto 1 week after onset of
  illness
 Overcrowding & Poor Sanitation
 No carrier state
CLINICAL FEATURES
 Incubation period 15 – 45 days
 Asymtomatic (90%):
  Clinically silent
  Nonspecific: Anorexia
                 Nausea
                 Vomiting
 Symptomatic (10%):
  Jaundice, Dark urine & Pale stools
CLINICAL COURSE

 Recovery: 3 – 6 weeks
 Extrahepatic complications: Arthritis,
                              Vasculitis,
                              Myocarditis
                             Renal failure
 Fulminant Hepatitis: Very Rare
DIAGNOSIS
 Anti HAV IgM +ve: Acute infection

  Disappears within

  3 months of recovery.




 Anti HAV IgG is of no diagnostic value

    as it persists years after infection.
TREATMENT
- DIET
 Raw juice diet for 3 to 5 days.
  Oranges, lemons, sugarcane and carrots may
  be used for juices. During this period, the
  bowels should be cleaned daily with
  lukewarm water enema.
 An all-fruit diet for further 3 to 5 days, with
  three meals a day at five-hourly intervals.
 Food especially beneficial: Limejuice, Pear, Barley
  water. Coconut water, sugarcane juice and radish
  leaves Juice.
 Avoid: Alcohol, Fried and fatty foods, too much butter
  and clarified
  butter, meats, tea, coffee, pickles, condiments and
  pulses.
- OTHER MEASURES
 1. Drink plenty of water with lemon juice.
  2. Adequate rest.
Prevention
 Vaccine - Formalin inactivated

2 doses 0, 6 -12 months

IM deltoid or gluteal

Protection period 25 yrs in adult &
 15 – 20 yrs in children
Hepatitis B virus (HBV)
  DNA virus (hepadnavirus).
 Complete virus particle is named Dane-particle,
 Genome is composed of incomplete double-
  stranded DNA.




             Dane’s particle
Route of transmission
Body fluids contain viral particles

   Semen

   vaginal secretions

   Blood

   Saliva
Route of transmission
 HORIZONTAL TRANSMISSION
 • Parenteral: Blood & blood products

              Injections

              Acupuncture needles

 • Sexual

 VERTICAL TRANSMISSION
 • Hbs Ag – positive mothers
Risk Groups
 Multiple sex partners
 IV drug abusers
 Hemodialysis patients
 Patients requiring repeated blood
  transfusions
  Hemophilia
  Thalassemia
 Health care workers
HBsAg


HBV DNAp
HBV DNA

HBcAg
Serological Markers of HBV
 HBsAg: Marker of infectivity
 Anti-HBs: Marker of immunity
 HBcAg: No commercial test available.
 Anti-HBc: Marker of past or current infection.
  IgM anti-HBc: Recent infection.
  IgG anti-HBc: Older infection.
 HBeAg: Marker of high degree of infectivity.
 Anti-HBe: May be present in infected or immune
  person.
Acute HBV Infection with Recovery


                Typical Serologic Course
                HBeAg                   anti-HBe

                    Symptoms
                                        Total anti-HBc
Titer

        HBsAg                   IgM anti-HBc                 anti-HBs




        0   4   8   12 16 20 24 28 32 36                52      100
                    Weeks after Exposure
Factors associated with the
    severity of hepatitis
 Infecting dose
  Higher the dose of HBV, shorter is
    incubation period and more severe
    hepatitis.
 Age
  Young age: mild initial hepatitis & more
    chance of chronicity.
 Immunological status
  Immunological impaired hosts: Milder
    initial disease.
CLINICAL COURSE
ACUTE ICTERIC HEPATITIS
 Incubation period - 70 days (30 - 180
 days);

 Four clinical stages:
   incubation period,
   prodromal phase (pre-icteric phase),
   icteric phase
   convalescence.
Pre-icteric phase
 Symptoms are nonspecific;

  Moderate fever

  Headache

  Malaise and weakness

  Anorexia, nausea, vomiting

  A vague, dull, right upper quadrant pain.
Icteric phase
 Clinical features of icteric phase:
   Symptoms of pre-icteric phase being mild;

   Jaundice (dark urine, skin and scleral icterus);

   Stool light or clay colored;

   Hepatomegaly

   Liver function abnormalities

     ALT and AST

     Bilirubin (direct & indirect)
Acute anicteric hepatitis

---No jaundice otherwise similar to acute
 icteric hepatitis,.
---The symptoms are less severe than
 that in acute icteric hepatitis.
DIAGNOSIS

SEROLOGY
 HBsAg

Anti HBcAg IgM

HBV DNA by PCR is most sensitive
 test
COMPLICATIONS
 Fulminant Hepatitis

 Chronic Hepatitis

 Rare complications:
    Pancreatitis,

    Myocarditis

     Atypical pneumonia

    Aplastic anemia

    Transverse Myelitis
CHRONIC HEPATITIS
 Chronic viral hepatitis: Inflammatory disease of the liver
> 6 months.

     CLINICAL FEATURES
 Fatigue, anorexia, abdominal distension, diarrhea
 are common, but they are fluctuant.

 Hepatomegaly, splenomegaly, hepatic facies, liver
 palms, spider angioma can be seen.
DIAGNOSIS
SEROLOGY
 HBsAg positive > 6 months

 Anti-HBc IgG in blood

 Serum HBV DNA > 105 copies/ml (20,000
 IU/ml)

 HBeAg or Anti HBeAg may be present
Differential               Diagnosis
 Acute hepatitis caused by other virus

   Epstein-Barr virus (EBV), Cytomegalovirus (CMV
 Hepatitis caused by nonviral infectious diseases

 Drug induced acute hepatitis

 Anoxic liver injury caused by

   Severe heart failure

   Cardiopulmonary arrest

 Alcoholic liver diseases
Treatment of Chronic Hepatitis B
 DRUGS : No specific therapy available
                      IFN
   Interferon-alfa              6 month in Hbe +ve
                      Peg IFN
                             12 months in Hbe - ve
     Lamivudine :100mg OD 48 weeks
     Adefovir : 10 mg OD 48 weeks
     Entecavir
     Telbivudine
 Liver Transplantation
 Role of Corticosteroids ???

  Sometimes recommended for two
  situations in acute viral hepatitis

   Cholestatic hepatitis

   Fulminant hepatic failure
PREVENTION
HBV Vaccine

  DNA Recombinant vaccine

  IM (deltoid but not gluteal)

  3 doses 0, 1, 6

  Duration of protection – 5 to 10 yrs
POST-EXPOSURE PROPHYLAXIS
  Combination of HBIG & HB vaccine (24 hrs)

 PERINATAL PROPHYLAXIS OF
 INFANTS
  HBIG 0.5ml IM in thigh immediately after birth

  Full course of HB vaccine started within 12 hrs
  of birth
HEPATITIS C
 Flaviviridae family.

 Single-stranded, positive-sense RNA
 virus,

 Also known as “Non A Non B Hepatitis”

 Route of transmission: Similar to HBV
Route of transmission
Similar to that of HB
Risk of Chronic Infection
 Intravenous drug abuse 95%

 Vertical transmission     3%
 Needle stick injury       3%
CLINICAL FEATURES
 Incubation period: 50 days (15 – 150 days)

 90% : Asymptomatic

 10%: Mild flu like illness with jaundice &
  raised serum amino transferrases

 Extrahepatic Manifestation : Arthritis

                             Glomerulonephritis
DIAGNOSIS

 HCV RNA detected in 1 – 2 weeks
 after infection
 Anti HCV is + ve 6 weeks after
 infection
Clinical Course
 85% : Chronic liver disease

 15 – 20% : Cirrhosis in 10 – 30 yrs

 7 – 15% of cirrhosis patient:
 Hepatocellular carcinoma
Treatment for Chronic HC
 For CHC: IFN-α + Ribavirin 6 - 12
 months
 Side Effects

   Ribavirin: Hemolytic anemia

   Interferon: Flu like symptoms

 Liver Tranplantation in Cirrhosis
Hepatitis D virus (HDV)
 Delta virus

 Incomplete defective RNA virus.

 Requires coating of hepatitis B surface antigen
  (HBsAg) for entry into and exit from the
  hepatocyte.
 HDV- antigen and Anti-HDV in serum

 Route of transmission: Similar to HBV
HBV - HDV Coinfection
                      Typical Serologic Course
          Symptoms

          ALT Elevated


Titre
                                          anti-HBs
          IgM anti-HDV



        HDV RNA

              HBsAg
                                   Total anti-HDV



             Time after Exposure
HBV - HDV Superinfection
                         Typical Serologic Course
          Jaundice
              Symptoms

                                      Total anti-HDV
                ALT
Titre




                         HDV RNA
               HBsAg


                                      IgM anti-HDV


                Time after Exposure
Hepatitis D Prevention

 Hepatitis D can be prevented by
 vaccinating susceptible persons with
 Hepatitis B vaccine
Hepatitis E virus(HEV)
 Single-stranded RNA,

 At least four Genotypes.

 Enterically trasmitted by contaminated water

 “Enterically Transmitted Non A Non B Hepatitis”

 Symptoms similar to Hepatitis A

 Self Limiting & no progression to chronic liver disease

 Incubation period: 40 days (15 – 60 days)
DIAGNOSIS

 ELISA for IgM & IgG anti HEV

 HEV RNA in serum or stools

             PREVENTION
  No vaccine available
Take home messages are
• Acute hepatitis can be caused by Viruses-
  A, B, C, D, E & others
• Treatment of acute hepatitis A is supportive,no
  need for hospitalization
• Hepatitis B virus
   100 times more infective than AIDS virus.
   No cure but easily preventable by vaccination
• Acute Hepatitis C HCV anti bodies appear late
  and are not protective.
Viral hepatitis 6

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Viral hepatitis 6

  • 1.
  • 2. DEFINITION Viral Hepatitis Inflammation of Liver caused by viral infection.
  • 3. VIRUSES  Hepatotropic viruses (Five types of Hepatitis Virus have been identified).  HAV, HBV, HCV, HDV, HEV Others:  HGV: Hepatitis G Virus TTV: Transfusion Transmitted Virus CMV: Cytomegalovirus EBV: Epstein-Barr Virus
  • 4. Hepatitis A virus (HAV)  Picornavirus single- stranded RNA genome,  Single serological type: Anti-HAV-IgM and Anti-HAV-IgG  Single antigen-antibody system  Replication - cytoplasm of liver cells.
  • 5. Epidemiology  Most common Viral Hepatitis  Source of Infection: patients.  Route of spread : Faeco-oral  Patient remains infectious 2 weeks prior to & for upto 1 week after onset of illness  Overcrowding & Poor Sanitation  No carrier state
  • 6. CLINICAL FEATURES  Incubation period 15 – 45 days  Asymtomatic (90%):  Clinically silent  Nonspecific: Anorexia Nausea Vomiting  Symptomatic (10%): Jaundice, Dark urine & Pale stools
  • 7. CLINICAL COURSE  Recovery: 3 – 6 weeks  Extrahepatic complications: Arthritis, Vasculitis, Myocarditis Renal failure  Fulminant Hepatitis: Very Rare
  • 8. DIAGNOSIS  Anti HAV IgM +ve: Acute infection Disappears within 3 months of recovery.  Anti HAV IgG is of no diagnostic value as it persists years after infection.
  • 9. TREATMENT - DIET  Raw juice diet for 3 to 5 days. Oranges, lemons, sugarcane and carrots may be used for juices. During this period, the bowels should be cleaned daily with lukewarm water enema.  An all-fruit diet for further 3 to 5 days, with three meals a day at five-hourly intervals.
  • 10.  Food especially beneficial: Limejuice, Pear, Barley water. Coconut water, sugarcane juice and radish leaves Juice.  Avoid: Alcohol, Fried and fatty foods, too much butter and clarified butter, meats, tea, coffee, pickles, condiments and pulses. - OTHER MEASURES  1. Drink plenty of water with lemon juice. 2. Adequate rest.
  • 11. Prevention  Vaccine - Formalin inactivated 2 doses 0, 6 -12 months IM deltoid or gluteal Protection period 25 yrs in adult & 15 – 20 yrs in children
  • 12. Hepatitis B virus (HBV)  DNA virus (hepadnavirus).  Complete virus particle is named Dane-particle,  Genome is composed of incomplete double- stranded DNA. Dane’s particle
  • 13. Route of transmission Body fluids contain viral particles  Semen  vaginal secretions  Blood  Saliva
  • 14. Route of transmission  HORIZONTAL TRANSMISSION • Parenteral: Blood & blood products Injections Acupuncture needles • Sexual  VERTICAL TRANSMISSION • Hbs Ag – positive mothers
  • 15. Risk Groups  Multiple sex partners  IV drug abusers  Hemodialysis patients  Patients requiring repeated blood transfusions Hemophilia Thalassemia  Health care workers
  • 17. Serological Markers of HBV  HBsAg: Marker of infectivity  Anti-HBs: Marker of immunity  HBcAg: No commercial test available.  Anti-HBc: Marker of past or current infection. IgM anti-HBc: Recent infection. IgG anti-HBc: Older infection.  HBeAg: Marker of high degree of infectivity.  Anti-HBe: May be present in infected or immune person.
  • 18. Acute HBV Infection with Recovery Typical Serologic Course HBeAg anti-HBe Symptoms Total anti-HBc Titer HBsAg IgM anti-HBc anti-HBs 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure
  • 19. Factors associated with the severity of hepatitis  Infecting dose Higher the dose of HBV, shorter is incubation period and more severe hepatitis.  Age Young age: mild initial hepatitis & more chance of chronicity.  Immunological status Immunological impaired hosts: Milder initial disease.
  • 21. ACUTE ICTERIC HEPATITIS  Incubation period - 70 days (30 - 180 days);  Four clinical stages:  incubation period,  prodromal phase (pre-icteric phase),  icteric phase  convalescence.
  • 22. Pre-icteric phase  Symptoms are nonspecific; Moderate fever Headache Malaise and weakness Anorexia, nausea, vomiting A vague, dull, right upper quadrant pain.
  • 23. Icteric phase  Clinical features of icteric phase:  Symptoms of pre-icteric phase being mild;  Jaundice (dark urine, skin and scleral icterus);  Stool light or clay colored;  Hepatomegaly  Liver function abnormalities  ALT and AST  Bilirubin (direct & indirect)
  • 24. Acute anicteric hepatitis ---No jaundice otherwise similar to acute icteric hepatitis,. ---The symptoms are less severe than that in acute icteric hepatitis.
  • 25. DIAGNOSIS SEROLOGY  HBsAg Anti HBcAg IgM HBV DNA by PCR is most sensitive test
  • 26. COMPLICATIONS  Fulminant Hepatitis  Chronic Hepatitis  Rare complications: Pancreatitis, Myocarditis  Atypical pneumonia Aplastic anemia Transverse Myelitis
  • 27. CHRONIC HEPATITIS Chronic viral hepatitis: Inflammatory disease of the liver > 6 months.  CLINICAL FEATURES Fatigue, anorexia, abdominal distension, diarrhea are common, but they are fluctuant. Hepatomegaly, splenomegaly, hepatic facies, liver palms, spider angioma can be seen.
  • 28.
  • 29. DIAGNOSIS SEROLOGY  HBsAg positive > 6 months  Anti-HBc IgG in blood  Serum HBV DNA > 105 copies/ml (20,000 IU/ml)  HBeAg or Anti HBeAg may be present
  • 30. Differential Diagnosis  Acute hepatitis caused by other virus Epstein-Barr virus (EBV), Cytomegalovirus (CMV  Hepatitis caused by nonviral infectious diseases  Drug induced acute hepatitis  Anoxic liver injury caused by  Severe heart failure  Cardiopulmonary arrest  Alcoholic liver diseases
  • 31. Treatment of Chronic Hepatitis B  DRUGS : No specific therapy available IFN  Interferon-alfa 6 month in Hbe +ve Peg IFN 12 months in Hbe - ve  Lamivudine :100mg OD 48 weeks  Adefovir : 10 mg OD 48 weeks  Entecavir  Telbivudine  Liver Transplantation
  • 32.  Role of Corticosteroids ??? Sometimes recommended for two situations in acute viral hepatitis  Cholestatic hepatitis  Fulminant hepatic failure
  • 33. PREVENTION HBV Vaccine  DNA Recombinant vaccine  IM (deltoid but not gluteal)  3 doses 0, 1, 6  Duration of protection – 5 to 10 yrs
  • 34. POST-EXPOSURE PROPHYLAXIS  Combination of HBIG & HB vaccine (24 hrs)  PERINATAL PROPHYLAXIS OF INFANTS  HBIG 0.5ml IM in thigh immediately after birth  Full course of HB vaccine started within 12 hrs of birth
  • 35. HEPATITIS C  Flaviviridae family.  Single-stranded, positive-sense RNA virus,  Also known as “Non A Non B Hepatitis”  Route of transmission: Similar to HBV
  • 36. Route of transmission Similar to that of HB Risk of Chronic Infection  Intravenous drug abuse 95%  Vertical transmission 3%  Needle stick injury 3%
  • 37. CLINICAL FEATURES  Incubation period: 50 days (15 – 150 days)  90% : Asymptomatic  10%: Mild flu like illness with jaundice & raised serum amino transferrases  Extrahepatic Manifestation : Arthritis Glomerulonephritis
  • 38. DIAGNOSIS  HCV RNA detected in 1 – 2 weeks after infection  Anti HCV is + ve 6 weeks after infection
  • 39. Clinical Course  85% : Chronic liver disease  15 – 20% : Cirrhosis in 10 – 30 yrs  7 – 15% of cirrhosis patient: Hepatocellular carcinoma
  • 40. Treatment for Chronic HC  For CHC: IFN-α + Ribavirin 6 - 12 months Side Effects  Ribavirin: Hemolytic anemia  Interferon: Flu like symptoms  Liver Tranplantation in Cirrhosis
  • 41. Hepatitis D virus (HDV)  Delta virus  Incomplete defective RNA virus.  Requires coating of hepatitis B surface antigen (HBsAg) for entry into and exit from the hepatocyte.  HDV- antigen and Anti-HDV in serum  Route of transmission: Similar to HBV
  • 42. HBV - HDV Coinfection Typical Serologic Course Symptoms ALT Elevated Titre anti-HBs IgM anti-HDV HDV RNA HBsAg Total anti-HDV Time after Exposure
  • 43. HBV - HDV Superinfection Typical Serologic Course Jaundice Symptoms Total anti-HDV ALT Titre HDV RNA HBsAg IgM anti-HDV Time after Exposure
  • 44. Hepatitis D Prevention  Hepatitis D can be prevented by vaccinating susceptible persons with Hepatitis B vaccine
  • 45. Hepatitis E virus(HEV)  Single-stranded RNA,  At least four Genotypes.  Enterically trasmitted by contaminated water  “Enterically Transmitted Non A Non B Hepatitis”  Symptoms similar to Hepatitis A  Self Limiting & no progression to chronic liver disease  Incubation period: 40 days (15 – 60 days)
  • 46. DIAGNOSIS  ELISA for IgM & IgG anti HEV  HEV RNA in serum or stools PREVENTION No vaccine available
  • 47. Take home messages are • Acute hepatitis can be caused by Viruses- A, B, C, D, E & others • Treatment of acute hepatitis A is supportive,no need for hospitalization • Hepatitis B virus  100 times more infective than AIDS virus.  No cure but easily preventable by vaccination • Acute Hepatitis C HCV anti bodies appear late and are not protective.