CHRONIC VIRAL

HEPATITIS

THE TERM VIRAL HEPATITIS

GENERALLY REFERS TO DISEASE

CAUSED BY THE 5 WELL-

DESCRIBED HEPATOTROPIC

VIRUSES, WHICH ARE DIVIDED

INTO ENTERAL AND

PARENTERAL GROUPS ON THE

BASIS OF THEIR MODE OF

TRANSMISSION

LABORATORY DIAGNOSIS

• AMINOTRANSFERASES (ALT, AST)
• BILIRUBIN
• PROTHROMBIN TIME (INR,

PROTROMBIN RATIO)

• SEROLOGIC MARKERS

HEPATITIS B VIRUS (HBV)

• Hepadnaviridae
• DNA VIRUS (the HBV genome is a

CIRCULAR, PARTIALLY DOUBLE-
STRANDED DNA)

• INCUBATION PERIOD: 1-6 MONTHS
• PARENTERAL TRANSMISSION (+++),

SEXUAL TRANSMISSION (+++),

PERINATAL TRANSMISSION (+++)

DIAGNOSIS

HBsAg (+)

IgG anti-HBc Ab (+)

HEPATITIS C VIRUS (HCV)

• NANB HEPATITIS
• Flaviviridae
• ss(+) RNA VIRUS (the HCV genome is

a SINGLE-STRANDED, POSITIVE-

SENSE RNA)

• INCUBATION PERIOD: 15-150 DAYS
• PARENTERAL TRANSMISSION (+++),

SEXUAL TRANSMISSION (+),

PERINATAL TRANSMISSION (+)

HEPATITIS D VIRUS (HDV)

• Deltaviridae
• INCOMPLETE RNA VIRUS

(REQUIRES HBsAg TO COMPLETE ITS REPLICATIVE CYCLE)

• INCUBATION PERIOD: 2-8 WEEKS
• PARENTERAL TRANSMISSION (++),
SEXUAL TRANSMISSION (++),
PERINATAL TRANSMISSION (+)

• CO-INFECTION / SUPERINFECTION

SPECIFIC AREAS THAT HAVE A

HIGH PREVALENCE OF HBV

CARRIERS INFECTED WITH

HDV INCLUDE the AMAZON

BASIN IN SOUTH AMERICA,

CENTRAL AFRICA, the

MEDITERRANEAN BASIN AND

the MIDDLE EAST.

TWO CLINICAL SCENARIOS

OF ACUTE HDV INFECTION

• COINFECTION WITH ACUTE HBV INFECTION

– RESULTS IN AN ACUTE HEPATITIS
INDISTINGUISHABLE FROM ACUTE
HEPATITIS B, BUT IT IS USUALLY SEVERE –
DEATH IN 2-20% OF CASES

• SUPERINFECTION IN A PATIENT

CHRONICALLY INFECTED WITH HBV –
THERE IS USUALLY A SIGNIFICANT
EXACERBATION OF PREEXISTING HBV
LIVER DISEASE

DIAGNOSIS

• CO-INFECTION
• IgM anti-HDV Ab

(+)

• HBsAg (+)
• IgM anti-HBc Ab

(+)

• SUPERINFECTION
• IgM anti-HDV Ab

(+)

• HBsAg (+)
• IgM anti-HBc Ab (-)

HEV INFECTION HAS RECENTLY

BEEN ASSOCIATED WITH CHRONIC

HEPATITIS IN SOLID

ORGAN-TRANSPLANT RECIPIENTS.

Kamar N, Selves J, Mansuy JM, et al.

„Hepatitis E virus and chronic

hepatitis in organ-transplant

recipients”.

N Engl J Med. Feb 21 2008;358(8):811-

7

THERAPY OF ACUTE VIRAL

HEPATITIS

TYPE

MAJOR FOCUS

COMMENTS

Hep A

Symptomatic therapy only

Observe for FHF 
OLT

Hep B

Symptomatic therapy;
consider oral therapy for severe
acute Hep B

Observe for FHF 
OLT

Hep C

(PEG)IFN-α therapy

TRT efficacious in

acute Hep C

Hep D

Vaccination against HBV
infection

Liver disease
clinically more

severe than Hep B
alone

Hep E

Symptomatic therapy only

FHF in pregnant
women

HBV IS A GLOBAL HEALTH

PROBLEM WITH AN

ESTIMATED 350 MILLION

HBV CARRIERS

WORLDWIDE AND 500 000

DEATHS EACH YEAR

PREVALENCE OF CHRONIC INFECTION WITH HBV,

BY COUNTRY, 2006 (CDC)

COMPLICATIONS OF CHRONIC

VIRAL HEPATITIS

• EXTRAHEPATIC MANIFESTATIONS OF

CHRONIC VIRAL HEPATITIS

• LIVER CIRRHOSIS
• HEPATOCELLULAR CARCINOMA (HCC)

EXTRAHEPATIC MANIFESTATIONS

OF HBV INFECTION

• POLYARTERITIS NODOSA
• GLOMERULONEPHRITIS
• CRYOGLOBULINEMIA (controversial)

EXTRAHEPATIC MANIFESTATIONS

OF HCV INFECTION

• CRYOGLOBULINEMIA
• GLOMERULONEPHRITIS
• IDIOPATHIC THROMBOCYTOPENIC PURPURA
• LICHEN PLANUS (controversial)
• Raynaud syndrome
• Sjögren syndrome
• Porphyria cutanea tarda
• Necrotizing cutaneous vasculitis
• Non-Hodgkin lymphoma

EVALUATION OF PATIENTS

WITH CHRONIC VIRAL

HEPATITIS

• AMINOTRANSFERASES
• HBV DNA (VIRAL LOAD) / HCV

GENOTYPE

• LIVER BIOPSY
• COMORBIDITIES / COINFECTIONS

TREATMENT OF CHRONIC

HEPATITIS B

INTERFERON

(without

RIBAVIRIN !!)

ORAL ANALOGS:
• LAMIVUDINE
• ADEFOVIR
• ENTECAVIR
• TENOFOVIR
• TELBIVUDINE

TREATMENT OF CHRONIC

HEPATITIS C

INTERFERON (IFN) + RIBAVIRIN (RBV)

THE BEST CHOICE IS PEG-IFN + RBV

Reduced Responsiveness for

antiviral therapy of chronic

hepatitis C

• Genotype 1
• HCV-RNA > 2 milion copies/ml
• Long-duration disease
• Age > 40
• Immunosupresion
• African American
• Obesity
• Hepatic steatosis
• Reduced adherence

MOST COMMON CAUSES OF

CIRRHOSIS IN THE UNITED

STATES

• HEPATITIS C (26%)
• ALCOHOLIC LIVER DISEASE (21%)
• HEPATITIS C plus ALCOHOLIC LIVER

DISEASE (15%)

• CRYPTOGENIC CAUSE (18%)
• HEPATITIS B, which may be

coincident with hepatitis D (15%)

PREVENTION

• GENERAL MEASURES

• PASSIVE IMMUNIZATION =

IMMUNOGLOBULIN

• ACTIVE IMMUNIZATION

=VACCINATION

HBV PREVENTION -

VACCINATION

SUCESSFUL VACCINATION NOT ONLY IS
EFFECTIVE IN PREVENTING HEPATITIS B
INFECTION BUT ALSO PREVENTS THE
SEQUELAE OF CHRONIC HEPATITIS B
INFECTION AND THIS IS THE FIRST
EXAMPLE THAT CANCER CAN BE
PREVENTED BY VACCINATION

HBV PREVENTION

• RECOMBINANT VACCINE (HBsAg)
• THE BEST VACCINATION SCHEDULE

IS 0-1-6 MONTHS

• PROTECTIVE LEVEL OF IMMUNE

RESPONSE AFTER VACCINATION IS
DEFINED AS LEVEL OF anti-HBs Ab
(GREATER THAN 10 IU/L)

PREVENTION OF PERINATAL

TRANSMISSION OF HBV

THE CURRENT RECOMMENDATION IS TO
PROVIDE PASSIVE-ACTIVE IMMUNIZATION TO
NEWBORNS OF CARRIER MOTHERS.
INFANTS SHOULD RECEIVE BOTH HBIG (0,06
mL/kg) AND VACCINE, AND THE FIRST DOSE OF
VACCINE SHOULD BE GIVEN WITHIN 12 HOURS
OF BIRTH AND THE SECOND AND THIRD DOSES
AT 1 AND 6 TO 12 MONTHS, RESPECTIVELY.
THIS REGIMEN HAS A PROTECTIVE EFFICACY OF
95%.

A combination vaccine

(Twinrix), which expresses both

HBsAg and hepatitis A virus, is

also available and is approved

for use in adults in the United

States and Europe. This

vaccine is typically used for

convenience when protection

against both viruses is needed.