Chronic viral hepatitis can be caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). HBV is responsible for 60-80% of hepatocellular carcinoma worldwide. HCV infection is the most common chronic blood-borne infection and a leading cause of cirrhosis and liver cancer. HDV requires HBV coinfection and can cause a more severe form of hepatitis. Treatment for chronic HBV and HCV infection involves antiviral medications like interferons, nucleoside analogs, and nucleotide analogs to achieve viral suppression and prevent disease progression.

1. CHRONIC VIRAL HEPATITIS

2. Introduction
• Chronic hepatitis represents a series of liver
disorders of varying causes and severity in
which hepatic inflammation and necrosis
continue for at least 6 months.
• Milder forms are nonprogressive or only
slowly progressive, while more severe forms
may be associated with scarring and
architectural reorganization, which, when
advanced, lead ultimately to cirrhosis, etc.

3. Older Classification
• 1. Chronic persistent hepatitis
• 2. Chronic active hepatitis
• 3. Chronic lobular hepatitis

4. Newer Classification
• The classification of chronic hepatitis is based
on
1. Cause
2. Histologic activity or grade
3. Stage or degree of progression

5. CAUSES OF CHRONIC HEPATITIS
• 1. Viral (HBV, HCV, HDV)
• 2. Drugs (alpha-methyldopa, isoniazid)
• 3. Alcoholic liver disease
• 4. Non-alcoholic steatohepatitis
• 5. Metabolic causes
– a. Primary biliary cirrhosis
– b. Sclerosing cholangitis
– c. Alpha-1-antitrypsin deficiency
– d. Wilson’s disease
– e. Haemochromatosis
• 6. Autoimmune hepatitis
– a. Type I (antiactin/lupoid)
– b. Type II (anti-liver kidney microsomal)
– c. Type III (anti-soluble liver antigen)
• 7. Cryptogenic

6. By Grade
Histologic Activity Index(HAI)
HAI Score
Knodell-Ishak score

8. By Stage

9. Hepatitis B Virus
• HBV is a DNA virus that belongs to the
hepadnavirus family.
• Eight genotypes of HBV have been identified and
labeled A through H.
• HBV (with or without cirrhosis) causes 60% to
80% of HCC worldwide.
• HBV-related mortality is estimated between
500,000 and 1,000,000 deaths worldwide per
year.
• HBV is an indication for l5% to 10% of the cases
of liver transplantation.

10. • Pathophysiology
HBV liver damage is immune mediated.
• Modes of transmission
Horizontal transmission
• Parenteral or percutaneous routes (e.g., needlestick
injury, injection drug use, hemodialysis, transfusions)
• Sexual contact (e.g., men who have sex with men,
sexual promiscuity, or intercourse with HBV-infected
partners)
• Vertical transmission: Mother to infant

11. • Chronic hepatitis B runs an indolent course,
sometimes for decades.
• Fatigue is a common symptom but frequently
overlooked because of its subjectivity. The
disease may only become clinically apparent
late in the natural course, with symptoms
typically associated with ESLD.
• Chronic HBV infection is a dynamic
process that occurs in different phases

12. Clinical course of HBV
Acute hepatitis B infection
Chronic HBV infection
3-5% of adult-acquired
infections
95% of infant-
acquired infections
Cirrhosis
Chronic hepatitis
12-25% in 5 years
Liver failureHepatocellular
carcinoma
6-15% in 5 years 20-23% in 5 years

16. • Chronic hepatitis B immune tolerant patients
and
• chronic hepatitis B with low
replication should not be treated.

17. • Three main groups:
1. IFNs,
2. Nucleoside analogs (entecavir),
3. Nucleotide analogs (tenofovir).

18. • The ideal treatment outcome is HBsAg loss
with seroconversion, unfortunately this goal is
rarely achieved.
• Therefore, in patients who are HBeAg positive
at baseline, the expected outcome is loss of
HBeAg with anti-e seroconversion, clearance
of HBV DNA, and normalization of liver
enzymes.

19. • In patients who are HBeAg negative at baseline,
the expected outcome is clearance of HBVDNA
and normalization of liver enzymes.
• In patients who are HBeAg positive at baseline,
treatment should be prolonged at
least 6 months after HBeAg loss/seroconversion.
• These patients should be monitored,
given the possibility of reactivation.

20. • In patients who are HBeAg negative at
baseline, treatment should be continued
indefinitely or until HBsAg loss/seroconversion
is achieved.

21. • Antiviral resistance is a phenomenon observed
with the use of nucleoside and nucleotide
analogs.
• Resistance should be considered in patients
with an HBV DNA level increase (.1 log10)
from the lowest level of suppression achieved
while on therapy.

22. • Tenofovir and entacavir have a high genetic
barrier for resistance (lowest susceptibility) when
compared to other nucleoside and nucleotide
analogs and are therefore the preferred oral
therapeutic agents

23. First Line
• Entecavir (ETV) oral nucleoside (guanosine)
analog Dose: 0.5 orally and 1 mg orally in case
of lamivudine resistance for 48 weeks.
• Tenofovir (TDF) oral nucleotide (acyclic)
analog Dose: 300 mg daily

24. INTERFERONS
• Antiviral, antiproliferative and
immunomodulatory effects.
• IFN-α and -β bind to the same receptor and have
predominantly antiviral effects.
• IFN-γ binds to a separate receptor and has more
marked immunoregulatory action but less potent
antiviral effects.
• Pegylation reduces rate of absorption,renal
clearance, decreases immunogenecity and
increases half life.

25. • IFN- α 2a and 2b—SC either 10 million units
thrice
• weekly or 5 million units daily for 4-6 months
or peginterferon α 2a 180 mcg weekly or 2b
100 mcg weekly for 48 weeks

26. Second Line
• Telbivudine (LdT) oral nucleoside (thymidine)
analog Dose: 600 mg daily
• Adefovir (ADV) oral nucleotide (adenosine)
analog Dose: 10 mg daily orally for 48 weeks
• Lamivudine oral nucleoside (dideoxy-3¢-
thiacytidine) analog Dose: 100 mg daily orally
for 48 weeks

27. Hepatitis C
• Classification
• HCV is an RNA virus that belongs to the
flavivirus family.
• There are six HCV genotypes with multiple
subtypes

28. • Epidemiology
• HCV is a global health problem with
approximately 180 million carriers
worldwide.
• The incidence of hepatitis C has declined in
the last 30 years.

29. • HCV infection is the most common chronic
blood-borne infection
• Transmission by transfusion of blood products
(and their derivatives) and organ
transplantation has been reduced to near zero
in developed countries due to sensitive
screening methods.

30. • Genotype 1 accounts for 75% and
genotypes 2 and 3 account for 20% of HCV
infections in the United States.

31. • 70% of cases of chronic hepatitis, 40% of cases
of ESLD, 60% of cases of HCC,
and 40% of liver transplantations.

32. • Pathophysiology
• The liver damage that ensues after HCV infection
is immune mediated.
• Modes of transmission include:
• Parenteral (e.g., transfusion, injection drug use,
body piercing, needlestick injury)
• Sexual (high-risk sexual practices) and from
mother to offspring (vertical transmission),
although at a much lower frequency than HBV

33. • Clinical Presentation
• The incubation period varies from 15 to 150
days.
• Acute hepatitis can be silent, especially in
children and young adults.

34. • Symptoms
may also vary from mild illness to ALF. Malaise, fatigue,
pruritus, headache abdominal pain, myalgias,
arthralgias, nausea, vomiting, anorexia, and fever are
common but nonspecific symptoms.
• Chronic hepatitis runs an indolent course, sometimes
for decades.
• Fatigue is a common symptom. The disease may only
become clinically apparent late in the natural course,
when symptoms are associated with advanced liver
disease.

35. Risk factors

36. Natural history

37. Diagnostic Testing
• Antibodies against HCV (anti-HCV) may be undetectable for
the first 8 weeks after infection. These antibodies are
detected by enzyme immunoassay (EIA).
• Antibodies do not confer immunity. The test has a
sensitivity of 95% to 99% and a lower specificity.
• A false-positive test (anti-HCV positive with HCV RNA
negative) may be detected in the setting of autoimmune
hepatitis (AIH) or hypergammaglobulinemia.
• A false-negative test (anti-HCV negative with HCV RNA
positive) may be seen in immunosuppressed individuals
and in patients on hemodialysis.

38. • HCV RNA can be detected by PCR in serum as
early as 1 to 2 weeks after infection
(qualitative and quantitative assays).
• It is expressed in international units
per milliliter (IU/mL), with lower limits of
detection approaching 10 IU/mL.
• HCV RNA determination is useful for both
diagnosis and treatment purposes.

39. • HCV genotypes and subtypes can be detected by
commercially available serologic and molecular
assays. HCV genotype influences the duration,
dosage, and response to treatment.
• Liver biopsy is useful to score the degree of
inflammation (grade) and fibrosis (stage) in the
liver of chronically infected patients.
• It is useful to grade the amount of liver steatosis
and guides treatment decisions.

40. Treatment
Goals Endpoints
• Viral eradication
• Prevention of disease
progression
 Sustained loss of HCV
RNA in serum (3-6
months post-Tx)
 Normalization of liver
enzymes
 Improved liver
histology
 Improved quality of
life

41. Treatment outcome in HCV is determined by a number of
pretreatment and ontreatment factors
Pretreatment factors
• Viral genotype, IL-28B
genotype (CC allele), viral
load, treatment naïve or
previous treatment failure,
advanced liver disease
(amount of liver fibrosis),
metabolism
• (obesity, steatosis, and
insulin resistance),
race/ethnicity
On-treatment factors
• Adherence to the
prescribed regimen,
• dose and duration of
ribavirin, pIFN-a, and
protease inhibitors
boceprevir and telaprevir
• Rapidity of viral clearance

42. Treatment
• In patients with genotype 1 (all subtypes), the standard
of care is to use triple therapy including pIFN, ribavirin,
and a direct antiviral agent (DAA).
• DAAs currently approved are boceprevir and
telaprevir.
• The chosen treatment regimen takes into consideration
prior exposure and response to pIFN and ribavirin,
presence of cirrhosis, and selected DAA
• Side effects of IFN-based therapy include flu-like
symptoms, neuropsychiatric disorders, endocrine
dysfunction, and bone marrow suppression.

45. HEPATITIS D
• Classification
• HDV is a circular RNA virus and is the only
member of the genus Delta virus.
• Originally, it was considered a subviral particle
resembling plant pathogens, viroids, and
virusoids.

46. • Epidemiology
• It is found throughout the world and is endemic
to the Mediterranean basin, the
Middle East, and portions of South America.
• Outside these areas, infections occur
primarily in individuals who have received
transfusions or in injection drug users.
• HDV requires the presence of HBV for infection
and replication.

47. • Pathophysiology
• HDV infection clinically presents as a
coinfection (acute hepatitis B and D),
• as a superinfection (chronic hepatitis B with
acute hepatitis D) that may progresses to
chronic infection and cirrhosis, or as a latent
infection (i.e., in the liver transplantation
setting).

48. • Risk Factors
• High-risk groups are similar to HBV (see
Epidemiology under Hepatitis B Virus
section).
• Prevention
• Although there is no vaccine to prevent HDV in
carriers of HBV, both infections
can be prevented by timely administration of the
HBV vaccine.

49. • Clinical Presentation
• In patients with coinfection, the course is
transient and self-limited.
• The rate of progression to chronicity is similar
to the one reported for acute HBV.
• In superinfection, the HBV carriers may
present with a severe acute hepatitis
exacerbation with frequent progression to
chronic HDV.

50. • Diagnostic Testing
• Diagnosis is made by finding HDV RNA or HDV
antigen in serum or liver and
by detecting antibody to the HDV antigen in
the setting of acute or chronic HBV.
• TREATMENT
• IFN-a is the treatment of choice for chronic
hepatitis D.

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