Chronic Viral Hepatitis powerpoint presentation .ppt

Chronic Viral Hepatitis powerpoint presentation .ppt

1. CHRONIC VIRAL CHRONIC VIRAL
HEPATITISHEPATITIS
Alfiya I. Fazulzyanova, MD, PhDAlfiya I. Fazulzyanova, MD, PhD
Department of Infectious DiseasesDepartment of Infectious Diseases
Kazan State Medical UniversityKazan State Medical University
20202020

2. OBJECTIVES:
•To review the etiology of chronic viral hepatitis
•To review the natural history of chronic viral hepatitis
(outcomes, relationship of chronic viral hepatitis and
cancer)
•To discuss patient management
•To discuss the current therapies for chronic viral
hepatitis

3. MAIN CONCEPTS
•Chronic viral hepatitis refers to inflammation
of the liver (hepatitis) that is caused by a virus
and lasts for longer than 6 months from the
moment of infection or the onset of illness:
- can move in a severe disease - cirrhosis
and hepatocellular carcinoma,
- remain long unchanged
- or regress under the influence of
treatment.

4. MAIN CONCEPTS
•Сlassification of chronic hepatitis
(adopted by World Congress of Hepatologists
in Los-Angeles in 1994)

–etiology (viral, autoimmune, drug-induced and
cryptogenic);
–the histological grade of disease activity;
–the stage of evolution in terms of fibrosis and
architectural derangement (cirrhosis).

5. Classification of chronic hepatitis (I)
•Form – chronic viral hepatitis B,C,D,
• mixed-hepatitis: double; triple (В+С; В+D+С)
• chronic non-verified viral hepatitis
•Activity grade:
Minimum (1-3) Moderate (9-12)
Mild (4-8) Severe (13-18)
•Stages:
0 – without fibrosis
I – mild fibrosis IV - cirrhosis
II – moderate fibrosis
III – severe fibrosis

6. Classification of chronic viral hepatitis by
disease phase (II)
■replicative phase with active infectious
process (high viremia, increased ALT,
clinical manifestations, inflammation in the
liver tissue);

■remission with low activity of the infectious
process (low viremia, normal ALT,
unexpressed clinical symptoms, reduction
of morphological changes

8. Hepatitis B
•The outcome following an exposure to hepatitis
B depends upon the immune response to the
virus:
Vigorous response immune clearance of infected liver cells
(acute hepatitis, but recover)
Partial response immune clearance of some, but not all,
infected cells; allows virus infection to persist by reinfecting new
cells (chronic hepatitis)
No response virus replicates and persists but no liver damage
(chronic inactive carrier; no symptoms)

9. Natural history of hepatitis B virus infection
and mechanism of disease progression
•Slowly progressive disease
•Complications of cirrhosis develop after 5–50+ years
•Progression of disease influenced by the phase of
viral replication and the incidence of hepatitis (ALT)
flares
•A recent liver biopsy is usually required for
assessment of disease stage

10. Chronic
HBV-infection
Autpatients
( 1 icteric/100-200
anicteric forms)
Acute HBV
Hospitalized
patients
(recovery 90-95%)
Chronic HBsAg
carrier state
(70-90%)
Chronic
hepatitis
(10-30%)
Cirrhosis
10-20%
Spontaneous
elimination of
HBsAg (1-2%/yr)
HCC
5-
10%
years
25-30 years
6 months
?
Natural history and outcomes of HBV-infection

11. Hepatitis B Virus - Definitions
Chronic Hepatitis B
1. HBsAg present for 6 months
2. Serum HBV DNA varies from undetectable to several billion IU/mL
3. Subdivided into HBeAg positive and negative.
HBV-DNA levels are typically >20,000 IU/mL in HBeAg- positive CHB,
and lower values (2,000-20,000 IU/mL) are often seen in HBeAg-negative CHB.
3. Normal or elevated ALT and/or AST levels
4. Liver biopsy results show chronic hepatitis with variable
necroinflammation and/or fibrosis
Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance
Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance

12. Hepatitis B Virus - Definitions
HbeAg-negative Chronic Hepatitis B
•Associated with variants in the precore or core promoter
region of the HBV genome
•Low or absent transcription of eAg
•Common in Europe and Asia, becoming more prevalent in
the U.S.
• Most common in HBV Genotype D, least common in
Genotype A
•Ongoing HBV replication and liver inflammatory activity
•May be associated with progressive liver disease, and
requires longer-term therapy

13. Hepatitis B Virus - Definitions
Inactive HBsAg carrier state
•HBsAg positive > 6 months
•HBeAg negative, HBeAb positive
•Serum HBV DNA <10
5
copies/ml
•Persistently normal ALT/AST
•Liver biopsy shows absence of significant hepatitis
•Reactivation may occur
•Patients remain at risk of HCC

14. Global distribution of CHB carriers:
350 million
Source: World Health Organization / Centers for Disease Control and Prevention

15. Hepatitis B Virus - Definitions
Hepatocellular Carcinoma
•Risk is high due to viral integration into the
host genome;
•May develop in the absence of cirrhosis or
after treatment with interferon;
•Has been reported in children;
•Hepatitis B carriers should be screened with
ultrasound and alpha fetoprotein;

16. Chronic HBV infections may be sub-divided, according to the level of HBV
replication and the strength of the host immune reactivity, into four phases:
Immune-Tolerant CHB
1. HBsAg present for 6 months
2. HBeAg positive
3. HBV-DNA levels are very high (typically >1 million IU/mL).
4. Normal or minimally elevated ALT and/or AST
4. Liver biopsy or noninvasive test results showing no
fibrosis and minimal inflammation
The infectivity is high and the histological activity minimal;
The duration of this phase is extremely variable, being longest in those
with perinatally acquired HBV;
Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance
Chronic hepatitis B - Chronic hepatitis B - Clinical course (1)

17. Immune-Active CHB
1. HBsAg present for 6 months
2. Serum HBV DNA >20,000 IU/mL in HBeAg-positive CHB
and >2,000 IU/mL in HBeAg-negative CHB
3. Intermittently or persistently elevated ALT and/or AST
levels
4. Liver biopsy or noninvasive test results show chronic
hepatitis with moderate or severe necroinflammation and
with or without fibrosis
Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance
Chronic hepatitis B - Chronic hepatitis B - Clinical course (2)

18. Inactive CHB
1. HBsAg present for 6 months
2. HBeAg negative, anti-HBe positive
3. Serum HBV DNA <2,000 IU/mL
4. Persistently normal ALT and/or AST levels
5. Liver biopsy confirms absence of significant
necroinflammation. Biopsy or noninvasive testing show
variable levels of fibrosis.
Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance
Chronic hepatitis B - Chronic hepatitis B - Clinical course (3)

19. HBV reactivation
loss of HBV immune control in HBsAg-positive, antiHBc–
positive or HBsAg-negative, anti-HBc–positive patients
receiving immunosuppressive therapy for a concomitant
medical condition;
a rise in HBV DNA compared to baseline (or an absolute
level of HBV DNA when a baseline is unavailable);
and reverse seroconversion (seroreversion) from HBsAg
negative to HBsAg positive for HBsAg-negative, anti-HBc–
positive patients
Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance
Chronic hepatitis B - Chronic hepatitis B - Clinical course (4)

20. HBeAg seroconversion:
loss of HBeAg and detection of anti-HBe in a
person who was previously HBeAg positive
and anti-HBe negative;
HBeAg seroreversion:
reappearance of HBeAg in a person who
was
previously HBeAg negative;

21. Symbols of Viruses
HBV DNA (“complete” virus)
HBsAg
”Defective” virus (HBsAg negative)
Д.Ш.Еналеева. В.Х.Фазылов. 2013.

22. HBsAg+
1. positive
hepatitis
HBsAg+
2. Reactivation
HBsAg+
3. Integrative
virogen
HBsAg —
4. Negative
hepatitis
The natural course of chronic hepatitis B in adults:
variants of the disease
HBeAg+
chronic hepatitis
HBeAg
—
, HBeAb
+
(HBeAg – negative chronic hepatitis
Wild strain
Mutant strain
Weeks - months
years DNA HBV
>2*10
8-10
МЕ/ml
DNAHBV
<2000 МЕ/ml
DNA HBV
>2*10
8-10
МЕ/ml
DNA HBV
<200 МЕ/ml
DNA HBV
-
АЛАТ
Д.Ш.Еналеева. В.Х.Фазылов. 2013.

23. Hepatitis C Virus (HCV)
•Discovered in 1989 as a small RNA blood-borne virus with
a large reservoir of chronic carriers worldwide;
•Major cause of posttransfusion hepatitis prior to 1992;
•Globally, an estimated 71 million people have chronic
hepatitis C infection;
•Major cause of chronic liver disease, cirrhosis, and
hepatocellular carcinoma worldwide.
•Approximately 399 000 people die each year from hepatitis
C, mostly from cirrhosis and hepatocellular carcinoma.
NIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2002, 2018

25. NATURAL HISTORY OF HEPATITIS C INFECTION

26. Chronic hepatitis C: clinical course
•Symptoms: 50% of patients report chronic fatigue
and right upper quadrant abdominal discomfort;
•Serum transaminases: persistently elevated in 43%,
intermittently elevated in 42%, normal in 15%;
•Risk factors for disease progression include:
alcohol use
co-infection with hepatitis B virus and/or HIV
early onset infection (<40 yo)
male sex

27. Hadziyannis SJ. J Eur Acad Dermatol Venereol. 1998;10:12-21.
HCV Infection:
Extrahepatic Manifestations
Hematologic
•Mixed cryoglobulinemia
•Aplastic anemia
•Thrombocytopenia
•Non-Hodgkin’s -cell lymphoma
Dermatologic
•Porphyria cutanea tarda
•Lichen planus
•Cutaneous necrotizing
vasculitis
Renal
•Glomerulonephritis
•Nephrotic syndrome
Endocrine
•Anti-thyroid antibodies
•Diabetes mellitus
Salivary
•Sialadenitis
Ocular
•Corneal ulcer
•Uveitis
Vascular
•Necrotizing vasculitis
•Polyarteritis nodosa
Neuromuscular
•Weakness/myalgia
•Peripheral neuropathy
•Arthritis/arthralgia
Autoimmune
Phenomena
•CREST syndrome

34. Diagnosis of Chronic Viral Hepatitis B
•ELISA:
–HBsAg (+/-)
–HBeAg (+/-)
–anti HBcor (IgM and IgG) (+)
–anti HBcor IgM (-/+)
–anti HBe (-/+)
•PCR DNA HBV (+/-)

35. Diagnosis of Chronic Viral Hepatitis C
•ELISA:
–anti HCV (IgM and IgG) (+)
–anti HCV IgG: core (+)
NS 3, NS 4, NS 5 (+/-)
–anti HCV IgM (-/+)
•PCR RNA HCV (+)

36. Liver Biopsy
•May be guided by CT or ultrasound
•Provides information regarding
–Degree of inflammation
–Disease severity
–Tissue damage
–Presence/absence of cirrhosis
•Helps determine
–Degree of disease progression
–Cause of liver disease
–Need for treatment / Patient Motivation
–Estimate chance of response

38. Ultrasound elastography
•radiologic technique for assessment of
hepatic fibrosis:
–Ultrasound elastography, commercially known as
FibroScan®, uses a modified ultrasound probe to
measure the velocity of a shear wave created by
a vibratory source;
–estimates of stiffness of the liver by ultrasound
correlate with fibrosis stage;
–can be performed in approximately 95% of
patients, although older patients and patients
who are obese can be more difficult to study.

39. The goal of antiviral therapy for chronic viral
hepatitis
•Sustained suppression of viral replication /
elimination of the pathogen

•Remission of liver disease
normalization of serum ALT levels
improvement in liver biopsy
•Improvement in clinical outcome
prevention of liver cirrhosis and HCC
increased survival

44. Thank youThank you