Viral Hepatitis B and C Epidemiology and management to Prevention

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Viral Hepatitis B and CEpidemiology and
management to Prevention

• Seyed Moayed Alavian M.D.
• Professor of Gastroenterology and Hepatology
• Director of Baqiyatallah Research Center for
  Gastroenterology and Liver Disease
• Editor-in-chief of Hepatitis Monthly
• E mail editor_at_hepatmon.com

World Hepatitis Day 2012
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Viral Hepatitis
Type of Hepatitis
Prevention
CDC fact sheets, available at www.cdc.gov
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Epidemiology of Hepatitis B

• Hepatitis B has a worldwide distribution and is
  perhaps the most common cause of chronic virus
  infection and the most frequent cause of chronic
  viral disease, cirrhosis, and hepatocellular
  carcinoma.
• Alavian SM, et al. Hepatitis B Virus Infection in
  Iran A Systematic Review. Hepat
  Mon20088(4)281-94.

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Hepatitis B Virus Infection Worldwide Disease
Burden
2 billion people are infected with HBV worldwide
with past infection
350 and 400 million persons are estimated
suffering this infection
15-25 will die from chronic liver disease
(liver cancer or cirrhosis)
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Geographic Distribution of Chronic HBV Infection

• Many of the data relating to the global
  distribution of HBV are over 10 years old
• More recent data suggest that this is an
  over-simplification
• There is an increasing trend towards
  HBeAg-negative HBV in many areas
• Global distribution of HBV is being affected by
  population movements from high prevalence areas

Chronic infection prevalence
Past infection prevalence
Predominant age at infection
40 90
? 8 High
Perinatal and early childhood
16 55
27 Intermediate
Early childhood
4 15
lt 2 Low
Adult
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HBV A Global Problem

• Hepatitis B infection is of major global
  importance
• large pool of patients
• serious nature of disease sequelae
• difficult/impossible to eradicate once chronic
  infection established
• significant economic burden
• Urgent actions are needed to address the problem
• immunisation programmes
• therapeutic intervention for chronically-infected
  patients
• education initiatives to prevent transmission/
• infection

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Burden of HBV

• Decreased life expectancy
• Loss of quality of life
• High lifetime costs associated with management of
  liver disease and sequelae of HBV infection
• HBsAg-positive patients
• more likely to be hospitalised
• longer hospital stays
• Healthcare costs increase with progression of
  CHB

Pereira. Transfusion 2003 Steinke et al. Gut 2002
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Modes of Transmission

• HBV is transmitted via contact with blood or body
  fluids in the same way as HIV. However, HBV
  is50100 times more infectious than HIV
• Modes of transmission
• perinatal/vertical
• child-to-child transmission
• unsafe injections and transfusions
• sexual contact

WHO Fact Sheet 2000
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Outcome of HBV Infection According to Age at
Time of Infection
of infections with outcome
Chronic infection
Symptomatic acute infection
Birth
16 months
712 months
14 years
Older children and adults
Age at infection
WHO 2001
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The Clinical Outcomes of HBV Infection
95
1070
Adult acute infection
Perinatal/childhood acute infection
Recovery
Recovery
lt 1
3090
lt 5
Fulminant hepatitis
? 1
Chronic infection
Inactive carrier state
Mild, moderate or severe chronic hepatitis
? 210
550 years
Cirrhosis
? 0.1
28
? 4
? 3
HCC
Decompensation
Transplant or
Death
per 100 patient-years
Adapted from EASL Consensus Statement. J.
Hepatol. 2003 39 (S1)S325
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Epidemiology Hepatitis B in Iran

• The prevalence of hepatitis B surface antigen
  (HBsAg) in Iran reported between 2.5 and 7.2 in
  1979. (1)
• In 1980s about 3 of population was affected
  (from 1.7 in Fars province to 5 in
  Sistan-Balouchestan province). (2)
• The most common routes of transmission
  was perinatal
• Farzadegan H ,1979, Merat S 2000

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Risk factors in chronic hepatitis B-Iran

• Age, male sex, history of contact with hepatitis
  B infected subject, extramarital sexual activity,
  injection drug use, major surgery, experimental
  dentist visit and some jobs (police, barber, and
  driver) were found to be independent risk factors
• It seems to be of great importance to pay more
  attention to certain jobs, life styles and
  cultural matters.
• Sali SH, Bashtar R, Alavian SM. Risk Factors in
  Chronic Hepatitis B Infection A Case-control
  Study. Hepat Mon20055(4)109-15.

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Transmission of HBV-Iran

• The seroprevalence of HBsAg positive in 1824
  subjects of Nahavand of Iran in 2002 was 2.3.
  History of surgery and imprisonment were the
  major risk factors for infection.
• The most Prevalent in relatives of index cases
  were sons and daughters (32.2 and 23.5),
  respectively.
• Alizadeh AH.., Alavian SM, et al. Seroprevalence
  of hepatitis B in Nahavand, Islamic Republic of
  Iran. East Mediterr Health J2006
  Sep12(5)528-37.

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Transmission of HBV-Iran

• Among 1500 subjects attended laboratory for
  sexually transmitted diseases in Northeast of
  Iran between 1998 and 2000, the seroprevalence of
  HBsAg was 10 in women and 14.2 in men
• Importance of Horizontal transmission in adults
• Ghanaat J 2003

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Transmission of HBV

• Risk factors in Iranian blood donors (1996-2000)
  in 2447 HBsAg cases
• HBsAg positivity in mother and family,
  transfusion history, male gender, hospital
  admission, sexual contact, and more age were risk
  factors.
• Alavian S,et al. Evaluation of Hepatitis B
  Transmission Risk Factors in Tehran Blood Donors
  In Persian. Govaresh 20043(9)169-75.

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Transmission of HBV-Iran

• In a study in 226 gypsies of Shahr-e-Kord,
  Southwest of Iran with a mean age of 20.7 years,
  thirty-five subjects (18) were HBsAg positive.
• Also, fifty-four persons (23.9) had positive HBc
  Ab.
• Tattooing and phlebotomy are common practices
  among our gypsies.
• Hosseini Asl SK 2004

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• In I.R. Iran mass vaccination of neonates against
  HBV infection was started from 1993 as a national
  program in routine neonates care. This program is
  supposed to affect the prevalence rate of HBV
  infection thorough the country and decrease the
  rate of infection after awhile.
• Zali 2005, Alavian 2007

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• More than one billion people have been immunized
  in the world since the beginning of
  implementation globally.

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Hepatitis B in general Population In Iran

• Using survey data analysis method the HBV
  infection prevalence in I.R. Iran estimated 2.14
  percent (95CI 1.92-2.35). The HBV infection
  prevalence in Iranian men and women estimated
  2.55 percent (95CI 2.25-2.85) and 2.03 percent
  (95CI 1.6-2.46 percent) respectively.
• Alavian SM, Hajariazdeh B, Ahmadzad Asl M,
  Kabir A, Bagheri Lankarani K. Hepatitis B Virus
  Infection in Iran A Systematic Review. Hepat
  Mon20088(4)281-94.

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• The distribution of HBV infection prevalence in
  the country showed that there are significant
  differences between provinces in HBV infection
  rates and the highest prevalence rates was in
  Golestan province (6.3 percent 95CI 3.2-9.3
  percent).
• Alavian SM, Hajariazdeh B, Ahmadzad Asl M, Kabir
  A, Bagheri Lankarani K. Hepatitis B Virus
  Infection in Iran A Systematic Review. Hepat
  Mon20088(4)281-94.

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• Vaccination in adult in Iran supported by
  changing of transmission rout from vertical and
  horizontal in childhood to horizontal in
  adulthood due to some risk factors.
• Alavian SM. Ministry of Health in Iran Is Serious
  about Controlling Hepatitis B. Hepat
  Mon200773-5.

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Vaccination against HBV in Iran

• After 13 years of implementation, the coverage
  has reached an appropriate level from 62 in 1993
  to 94 in 2005.
• Deputy for Health, CDC report (Iran) 2006

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• Mass vaccination in high risk group and
  susceptible groups, mainly women at reproductive
  ages, youth and high risk job workers such as
  health care providers, barbers, drivers and
  intravenous drug abusers.
• Adult vaccination
• People awareness
• Early diagnosis

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Hepatitis B in CRF

• Hemodialysis patients are highly exposed to be
  infected with hepatitis B virus .Primary
  prevention with vaccination is the most effective
  strategy to reduce morbidity caused by HBV
  infection and hemodialysis patients are strongly
  recommended to be vaccinated against HBV.
• The prevalence of HBsAg positivity had decreased
  from 3.8 in 1999 to 2.6 in 2006 in Iran.
• Alavian SM, Bagheri-Lankarani K, Mahdavi-Mazdeh
  M, Nourozi S. Hepatitis B and C in dialysis units
  in Iran Changing the epidemiology. Hemodial
  Int2008 Jul12(3)378-82.

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When should hepatitis B not be treated?
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Clinical Case-1 -Normal ALT

• A 25 years-old male, born from HBs Ag positive
  mother,
• Diagnosed in screening for HBV due to his mother
  histroy
• No past history of acute hepatitis or jaundice
• PE Normal
• AlT Normal, HBeAg Positive, HBV Viral Load
  2,000,000 copies/ml
• What is you next plan?

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Clinical Case-2 Inactive carrier

• The patient is a 20 year old woman who is HBs Ag
  (), HBe Ag (-).
• Her HBV DNA is 5000 copies/mL.
• She has mild chronic portal inflammation, no
  fibrosis with mild steatosis.
• Her serum ALT is 30 IU/L (upper limit of normal
  40 IU/L).
• She is obese.
• What is your plan for this patient?

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Characteristic phases of CHB infection
Immune
Immune
Immune
Immune
escape
tolerance
clearance
control
HBeAgve
HBeAgve
lt
lt
gt
gt
HBV-DNA
ALT
HBeAg ve chronic hepatitis
HBeAg ve/ve active chronic hepatitis
Inactive (carrier) state
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Who should be considered for treatment?
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Who should be considered for treatment?
monitor
monitor
treat
treat
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Immune Tolerant Phase

• Commonly perinatally transmitted
• Frequently in Foreign-born individuals
• A patient may traverse through phases
• 10-30 years
• Persistently elevated HBV DNA levels contribute
  to increased risk of HCC

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Current AASLD Practice Guidelines

• Low efficacy with current treatment
• Observe, consider treatment if ALT becomes
  elevated
• Consider biopsy aged gt40, ALT persistently
  elevated, family hx HCC
• Consider treatment HBV DNA gt20,000 IU/mL AND
  biopsy shows mod/sev inflammation and significant
  fibrosis

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Cut off Level for ALT AST
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HBeAg Positive Patients Immune-Tolerant vs HBeAg
Active CHB
Immune-Tolerant HBeAg Active CHB
Age Young (lt35 yrs) Young or older
ALT Persistently normal Elevated or fluctuating
HBV DNA Usually very high gt107 IU/mL Variable but gt104 IU/mL
Liver histology Minimal or no fibrosis and inflammation Necroinflammation fibrosis
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Role of ALT in the assessment liver disease in
CHB

• Serum ALT level may not accurately predict
  histologic stage14
• Up to 24 of patients with normal ALT have stage
  24 fibrosis by biopsy5,6
• Liver biopsies should be employed more
  frequently in normal ALT, especially for
  patients gt3040 years of age5
• Treat if there is significant disease on liver
  biopsy7,8

1. Kim HC et al. BMJ 2004 328 9836 2. Nguyen
MH et al. Hepatology 2005 42 593A 3. Wang C
et al. Hepatology 2005 42 573A 4. Lai M et al.
J Hepatol 2007 47 7607 5. Lai M et al.
Hepatology 2005 42 (Suppl 1) 720A 6. Alberti A
et al. Ann Intern Med 2002 137 9614 7. Keeffe
EB et al. Clin Gastroenterol Hepatol 2006 4
93662 8. Lok ASF, McMahon B. Hepatology 2007
45 50739.
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• Persistently normal ALT was associated with
  excellent long-term prognosis
• Increasing ALT levels of at least 2 times ULN
  during follow-up was associated with increasing
  morbidity and mortality.
• ALT of at least 2 times ULN is therefore an
  appropriate threshold for anti-HBV therapy

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Chronic HBV Goals of Therapy

• HBV is probably never cured but rather controlled
  by limiting viral replication
• Markers of treatment response
• Decreased serum HBV DNA to low or undetectable
  levels lt10-15 IU/mL
• Decreased or normalized serum ALT levels
• Induce HBeAg loss or seroconversion (in
  HBeAg-positive patients)
• Induce HBsAg loss or seroconversion
• Improved liver histology

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HBsAg carrier state

• ALT q 3 months for 1 year, if persistently
  normal, ALT q 6-12 months
• If ALT 1-2 ULN, check serum HBV DNA level and
  exclude other causes of liver disease.
• Consider liver biopsy if ALT borderline or mildly
  elevated on serial tests or if HBV DNA
  persistently 10,000 C/mL.
• Consider treatment if biopsy shows
  moderate/severe inflammation or significant
  fibrosis
• Consider screening for HCC in relevant population

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Recommendations

• Any decision for treatment and/or liver biopsy in
  patients with CHB should be made according to
• HBe Ag
• ALT
• Viral load
• Age
• Family history
• Presence of comorbid diseases

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We dont treat patients in immune tolerance phase

• HBeAg , very High HBV DNA, Persistently normal
  ALT, young age
• But, Family history is very important

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Management of Chronic Carrier Patients (Low
replicative phase)

• Treatment not indicated but
• Need to confirm persistently normal ALT
• Need to confirm persistently HBV DNA lt 2000
• Monitor for transition to reactivation with ALT
  measurements q3-6 months
• Monitor for HCC with US and AFP
• Style life modification

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• We dont treat patients in low replicative phase
  (chronic carrier patients)
• And think about other factors in elevated ALT
  such as fatty liver

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Hepatitis C Virus Infection
46
Epidemiology of Hepatitis C

• HCV infection is widespread throughout the world.
  
• WHO estimation suggests that up to 3 of the
  worlds population have been infected with HCV.

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Relative Efficiency of HBV, HCV, HIV Transmission
by Type of Exposure
Type of exposure Efficiency of transmission to
infected source HBV HCV HIV Transfusion
Injecting drug use Unsafe
injections Perinatal Needl
e stick Sexual Non-intact
skin /- /-
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Risk Factors Associated With Acquiring HCV
Infection

• Transfusion, transplant from infectious donor
  (1992)
• Injecting drug use and Incarceration
• Occupational blood exposure (needle sticks)
• Birth to an infected mother
• Infected sex partner
• Multiple heterosexual partners
• Tattooing
• Health-care related transmission

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Determining Who to Screen

• Primary care offices are the frontline in
  identifying patients with risk factors
• Anyone with a history of IDUs (even limited)
  should be tested
• Persons with a history of no injection drug use
  and/or multiple sexual partners should also be
  screened for HCV
• Persons infected with HIV should be screened for
  HCV
• Any abnormal ALT level warrants HCV testing

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Decrease or emerging infection?

• With the implementation of mandatory HCV
  screening of blood and blood products in the
  early 1990s, the number of post-transfusion
  infections has already decreased dramatically.
  However, intravenous drug use (IDU) has
  accelerated in the world.

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Epidemiology of Hepatitis C

• First report in Iran is related to Rezvan et al
  in 1994 in IBTO 0.3 of blood donors in Tehran.
• Rezvan et al. Vox Sang 1994

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Alavian et al. J Gastro Hepatology 2002(
0.12 were HCV positive)
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Alavian et al. J Gastro Hepatology 2002(
0.12 were HCV positive)
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IUDs / Prisoners and HCV in Iran

• First report in Prison by Prof Zali in 2001, IUDs
  in Ghasr prison in Tehran (study time spring
  1995) 40.1 HCV
• Is it a serious problem? History of tattooing and
  cupping were important
• Zali 2003

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In a study in three prisons in three central
provinces of Iran (Isfahan, Lorestan, Chaharmahal
va Bakhtiari) in 2003 in male prisoners who were
arrested because of their addiction

• 3.5 were HBsAg positive and 35.8 were HCV
  antibody.
• According the age, the infection with HBV and
  HCV were more common in younger than 30 yr old.
• Isfahan , Lorestan and Chaharmahal va Bakhtiari
  Addicted arrested respectively, 28.5, 50 ,
  53. HCV infected
• IUDs, Tattooing history, In jail more than 5
  years were important
• In Conclusion Potentiating of harm reduction
  program ,Education for dangerous behavior,
• Javadi 2006

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Strategies for control

• Community-wide education initiatives are needed
  for alerting people to the modes of transmission
  and facilitating a social climate at-risk people
  feel comfortable to seek testing and where
  harm-reduction strategies can be implemented.

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• Screening for IDU Efficiently Identifies Most
  HCV-Positives
• Harm reduction messages more HCV-specific
• And focus on All drug equipments, not just
  needles/syringes

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Alavian SM, Tabatabaei SV. Epidemiology and Risk
Factors of HCV Infection among Hemodialysis
Patients in Eastern Mediterranean Countries a
Quantitative Review of Literature, archive of
medical research (in press) 2010
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Epidemiology of HCV in Thalassemia patients in
EMRO
Alavian SM, Tabatabaei SV. Epidemiology of HCV
Infection among Thalassemia Patients in Eastern
Mediterranean Countries a Quantitative Review of
Literature . European journal of epidemiology (in
press) 2010
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• Lack of strict adherence to universal precautions
  by staff and sharing of articles such as
  multidose drugs might be the main mode of
  nosocomial HCV spread among HD patients

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Strategies for control

• Community-wide education initiatives are needed
  for alerting people to the modes of transmission
  and facilitating a social climate at-risk people
  feel comfortable to seek testing and where
  harm-reduction strategies can be implemented.