Hep b

1. Mentored By
Dr N.S. Rawat Sir
Sr. prof. & Unit Head
Unit- C, General Medicine
Present By
Dr Mahendra Kumar
2nd Year Junior Resident
Unit-C, General Medicine

2.  HAV is responsible for 10-30% of acute hepatitis and 5-15% of acute liver failure
cases in India
 HEV 10-40% of acute hepatitis and 15-45% of acute liver failure
 Hepatitis B surface antigen (HBsAg) positivity in the general population ranges from
1.1% to 12.2%, with an average prevalence of 3-4%
 Anti-Hepatitis C virus (HCV) antibody prevalence in the general population is
estimated to be between 0.09-15%

3.  Approximately 40 million people chronically infected with Hepatitis B
Virus (HBV) and 6-12 million people with Hepatitis C in India
 Chronic HBV infection accounts for 40-50% of HCC and 20-30% cases
of cirrhosis
 Chronic HCV infection accounts for 12-32% of hepatocellular carcinoma
(HCC) and 12-20% of cirrhosis.

4. Aim
1. Combat hepatitis and achieve country wide elimination of Hepatitis C by
2030
2. SDG goal – 3 Target 3.3 - By 2030, end the epidemics of hepatitis.
3. Achieve significant reduction in the infected population, morbidity and
mortality associated with Hepatitis B and C viz. Cirrhosis and Hepato-
cellular carcinoma.
4. Reduce the risk, morbidity and mortality due to Hepatitis A and E

5. Key Objectives
1) Enhance community awareness on hepatitis
2) Provide early diagnosis and management
3) Develop standard diagnostic and treatment protocols for management of
viral hepatitis and its complications.
4) Strengthen the existing infrastructure facilities
5) Develop linkages with the existing National programmes towards
awareness, prevention, diagnosis and treatment for viral hepatitis.
6) Develop a web-based registry of patients

6. Program Management
The main activities of program would include the following
 Prevention
 Diagnosis and Treatment
 Monitoring and evaluation, surveillance and research
 Training and capacity building

7. Prevention
Awareness generation
ante-natal screening of pregnant women for Hepatitis
tracking mechanism to ensure institutional delivery for all Hepatitis B carrier
pregnant women.
Immunization for hepatitis B – increase hepatitis B birth dose, high risk group, health
care workers
safe injection practices
Blood safety
periodic testing of drinking water sources
Improved IEC for prevention and checking transmission

8. Diagnosis and Treatment
 Screening – serological tests
 Confirmation – molecular test
 Treatment of uncomplicataed cases
 Treatment of complicated cases
 Referral and linkage
 Standard treatment protocol for viral hepatitis
 Uniterrupted supply of drugs
 Training of health care staff

9. Monitoring and Evaluation, Surveillance and Research:
1. To develop Viral Hepatitis Information Management System (VHIMS) for
i. registry of patients
ii. Tracking of patients for compliance.
2. Co-ordinate with the National Viral Hepatitis Surveillance Program
3. Research: Identify evidence based operational research and implement
Training and capacity building
1. Standardized training module
2. Digital and conventional training
3. E- learning
4. Facilitations through teleconsultation

10. The NVHCP coordinated by the units
at the centre and the states.
1) National Viral Hepatitis management unit (NVHMU)
2) State Viral Hepatitis management unit (SVHMU)
3) District Viral Hepatitis management unit (DVHMU)

12. Service Delivery
Service Delivery Component will include the following two aspects:
 Synergies with the existing programs and relevant ministries of
Government of India
 Diagnosis and Management of Viral Hepatitis with focus on
treatment of Hepatitis B&C

13. Synergies with the existing programs
 Universal Immunization Program
 National AIDS Control Program (NACP)
 Safety of blood and blood products
 Harm reduction in key populations
 Injection safety and infection control
 Integrated Disease Surveillance Programme (IDSP)
 Swachh Bharat Mission- Urban & Rural
 Ministry of Drinking Water and Sanitation
 Food Safety and Standards Authority of India (FSSAI)

14. Hepatitis A infection
 HAV is a non-enveloped RNA virus belonging to the picornavirus family
 Transmission - fecal-oral route.
 incubation period of around 15-45 days.
 Excretion in the stool occurs for only 7-14 days after the onset of the
clinical illness and is diagnostic of an acute HAV infection.

15.  No carrier state has been identified.
 Constitutional symptoms precede onset of jaundice by 1-2 weeks.
 Dark urine and clay colored stools
 With the onset of clinical jaundice the prodromal constitutional
symptoms usually diminish
 The liver becomes enlarged and tender

16. Laboratory diagnosis of Hepatitis A
infection
 HAV has an incubation period of ~4 weeks. Its replication is limited to the liver,
but the virus is present in liver, bile, stools and blood during late incubation
period and acute pre-icteric phase of illness.
 In acute hepatitis with clinical jaundice, the serum bilirubin levels are above
2.5mg/dL and serum alanine aminotransferase (ALT) is more than 10 times the
upper limit of normal.

17. 1. IgM antibodies against HAV indicate acute
infection.
2. IgG antibodies against HAV becomes the
predominant antibody during convalescence
and remains detectable indefinitely. indicate
immunity to hepatitis A either because of past
infection or vaccination.

18. Management
 There is no role for antiviral therapy
 The case fatality is very-very low (~0.1%) but is increased in
advanced age and in the presence of underlying debilitating
diseases.
 Infection in the community is best prevented by improving social
conditions especially overcrowding and poor sanitation.

19. Hepatitis E infection
 HEV is non enveloped single stranded RNA virus of Hepevirus family
 Fecal oral route transmission
 Incubation period 14-70 days.
 Illness began after incubation period as non specific symptoms then jaundice
 HEV infection not clinically distinguishable from other viral hepatitis , diagnosis
suspected on epidemiologic setting. Definitive with IGM Ab in blood.
 Disease is self limiting , no specific treatment required
 Hospitalization is required for people with fulminant hepatitis and symptomatic
pregnant woman.

20. Hepatitis B infection
 HBV, a double-stranded DNA virus, belongs to the family of
hepadnaviruses.

22. Transmission
 Perinatal transmission and occasionally horizontal transmission early in life
are most common in high prevalence areas.
 Sexual contact and percutaneous transmission also contribute to the
transmission of HBV
incubation period for HBV varies from 30-180 days.

23. Clinical Presentation
 The spectrum of clinical manifestations of HBV infection varies in both acute and chronic
disease.
Actue phase of Hepatitis B
 subclinical or unicteric hepatitis to icteric hepatitis and, in some cases, fulminant hepatitis.
 Approximately 70 percent of patients - subclinical or unicteric hepatitis,
30 percent develop icteric hepatitis
 Fulminant hepatitis B is unusual - 0.1 to 0.5 percent of patients

26. Treatment for acute phase of HBV
• mainly supportive. In addition prevent infection in exposed contacts,
• decision to hospitalize patients should be taken on a case-to-case basis. Patients,
who have a coagulopathy, are deeply jaundiced, or encephalopathy or older
patient with other comorbidities should generally be hospitalized.
• In acute cases, the patients who have fulminant hepatitis or hepatitis B with
underlying cirrhosis should be considered for antiviral treatment.

27. Chronic phase of Hepatitis B
 asymptomatic carrier state to chronic hepatitis, cirrhosis, and HCC. Extra-hepatic
manifestations of infection
 Some patients experience exacerbations of the infection which may be
asymptomatic, mimic acute hepatitis, or manifest as hepatic failure.
 Physical examination may be normal, or may be Jaundice, splenomegaly, ascites,
peripheral edema, UGI bleed and encephalopathy in decompensated cirrhosis.

28.  Laboratory tests may be normal or have a mild to moderate elevation in serum AST and ALT.
 ALT concentration may be as high as 50 times the upper limit of normal
 alfa-fetoprotein (AFP) concentrations as high as 1000 ng/mL may be seen.
 cirrhosis is suspected when there is evidence of hypersplenism or impaired hepatic synthetic
function (hypoalbuminemia and/or prolonged prothrombin time/ international normalized ratio
(INR).
 Extrahepatic manifestations - Polyarteritis nodosa and glomerular disease

29. Natural Course and Phases of Chronic
Hepatitis B Infection
1. Replicative phase: Immune tolerance
2. Replicative phase: immune clearance
3. Low or non replication phase/ inactive carrier state
4. Immune escape/ Reactivation
(HBeAg negative chronic hepatitis)

30. 1. Replicative phase: Immune tolerance
 In patient with perinatally acquired HBV infection
 Last for 10-30 years
 High level of HBV replication – high HBeAg and HBV DNA in
serum
 No evidence of liver disease as Lack of symptom, normal
serum ALT, and minimal changes in liver biopsy
 No immunologic response

31. 2. Replicative phase: immune clearance
 Occur in 2nd and 3rd decade in patient with perinatally acquired
HBV infection
 Spontaneous HBeAg clearance increase
 HBeAg seroconversion frequently but not always
 Clearance of HBV DNA
 Abrupt increase in serum ALT due to increase Immune mediated
lysis of infected hepatocyte
 Abortive immune clearance- not all exacerbation lead to HBeAg
seroconversion and clearance of HBV DNA

32. 3.Low or non replication phase/
inactive carrier state
 Negative HBeAg
 Anti- HBe positive
 HBV DNA undetectable or very low in serum
 Liver disease in remission as evidence by normal serum ALT
 HBsAg<1000 IU/ml in an HBeAg negative patient with serum HBV
DNA <2000 IU/ml identifies inactive carrier phase with a high
diagnostic accuracy (94%)

33. 4. Immune escape/ Reactivation
(HBeAg negative chronic hepatitis)
 Progression from HBeAg negative inactive phase to HBeAg negative
hepatitis B with mutation in core or core promotor region of HBV
genom
 HBeAg negative but with continued HBV replication and progression
in liver disease

35. Routine assessment of HBsAg positive person
1. Serological markers of HBV infection
2. Measurement of HBV DNA levels
3. Assessing severity of liver disease

36. Measurement of HBV DNA levels
 By real time polymerase chain reaction (rtPCR)
 Correlate with disease progression
 Differentiate HBeAg negative disease from inactive chronic infection
 Useful to take decision for treatment
 Use for optimal monitoring of response to antiviral therapy

37. Assessing severity of liver disease
 Clinical evaluation for features of cirrhosis and evidence of decompensation
 Liver enzymes
 Non-invasive tests (NITs)
a)aspartate aminotransferase (AST)-to-platelet ratio index (APRI),
b)FIB-4
c)elastography (FibroScan).
presence of cirrhosis (APRI score >2: FIB 4 >3.25 in adults)
Liver biopsy

38. Management

39. Whom not to treat

40. Selection of antiviral drug for CHB:
 In all adults, adolescents and children aged 12 years or older in whom
antiviral therapy is indicated, the NAs which have a high barrier to drug
resistance (tenofovir or entecavir) are recommended.
 In woman of childbearing age Tenofovir may be preferred as the drug of
choice in the eventuality of a pregnancy. Entecavir is not recommended
in pregnancy.
 Tenofovir is preferred in patients who have been exposed to lamivudine
who have a potential for Entecavir resistance.
 Entecavir is recommended in children aged 2–11 years.
 Entecavir may be preferred over Tenofovir in: -
Age > 60 years
bone disease
altered renal function

41.  Tenofovir alafenamide fumarate ( TAF) is the drug of choice in patients with
reduced renal function or bone disease bone toxicities, where entecavir is
contraindicated
 Drugs with a low barrier to resistance (lamivudine, adefovir or telbivudine) are
available but not recommended as they lead to drug resistance.

44. Monitoring for tenofovir
Measurement of baseline renal function includes: serum creatinine (Cr) levels,
and calculation of creatinine clearance (CrCl)/estimated glomerular filtration
rate (eGFR) using the Cockcroft–Gault (CG)
CG formula: eGFR = (140 – age) x (weight in kg) x 0.85 (if female) / (72xCr in
mg/dL)

45. HBV in Pregnancy
 All pregnant women with HBV should be evaluated for the need of treatment
for hepatitis B and any associated liver disease, and given advice about
prevention of transmission.
 Hepatitis B in a pregnant woman is not a reason for considering termination of
pregnancy. Similarly, the need for caesarean delivery should be decided based
on obstetric indications, and not on the presence of HBV infection.
 Administration of hepatitis B vaccine to pregnant women with HBV provides
no benefit either to the mother or the baby.

46. When drug given to pregnant woman
1. HBsAg +
APRI Score >2
FIB 4 Score >3.25
(evidence of cirrhosis)
Treatment recommended irrespective of ALT & HBV DNA level.
2. HBsAg +
APRI Score <2
FIB 4 <3.25
No Cirrhosis , But if persistently elevated ALT & HBV DNA is >20,000 iu/ml. Treatment
recommended.

47. 3. If HBV DNA is <20,000 or Not detected then Treatment is recommended only when APRI
Score >1.5 , FIB 4 > 1.45 or platelets <100,000.
4. If ALT not elevated persistently & HBV DNA >2000 iu/ml. Treatment recommended only
when APRI >1.5.
5. if ALT not persistently elevated & HBV DNA <2000 , No treatment recommended. requires
follow up.
Drug of choice is Tenofovir , may be started after 3 months or 7 months of Pregnancy
depending upon test reports n cirrhosis evidence...
Continue treatment even during brest feeding.

48. Care of the baby
Immunoprophylaxis of hepatitis B virus infection
Hepatitis B immunoglobulin (HBIG) may provide some additional protection in situations where risk of
transmission is particularly high – i.e. babies born to mothers with hepatitis B who also have
detectable HBeAg and/or high viral load
Breast feeding - A mother who has hepatitis B may breast feed her baby, unless there is an exuding
injury or disease of the nipple or surrounding skin. The advantages of breast feeding far outweigh the
risk, if any, of transmission of hepatitis B to a baby who has received hepatitis B vaccine.
Timing of testing If it is felt that the baby needs to be tested for hepatitis B, this should be done only
after 1 year of age. Any positivity before this age is difficult to interpret and may resolve spontaneously
over time

49. All persons with cirrhosis based on clinical evidence (or APRI score >2 in adults)
require lifelong treatment
Discontinuation may be considered in patients without cirrhosis: •
With persistent HBsAg loss after one year of consolidation treatment
(regardless of prior HBeAg status or availability of HBV DNA levels)
HBeAg loss and sero-conversion to Anti-HBe after completion of one year
(preferably 3 years) of additional treatment with persistently normal ALT
levels and undetectable HBV DNA levels.
When To Stop Treatment

50. Careful long term monitoring for reactivation with serial 3-6
monthly HBeAg, ALT and HBV DNA levels is mandatory in those
who have discontinued treatment for consideration of
retreatment
Retreatment is recommended if there are consistent signs of
reactivation (HBsAg or HBeAg becomes positive, ALT levels
increase, or HBV DNA becomes detectable again)

51. Monitoring

52. Monitoring for hepatocellular carcinoma (HCC)
Routine surveillance for HCC with abdominal ultrasound and alpha-
fetoprotein testing every six months is recommended for:
Persons with cirrhosis, regardless of age or other risk factors
Persons with a family history of HCC
Persons aged over 40 years (lower age may apply
according to regional incidence of HCC), without clinical
evidence of cirrhosis (or based on APRI score ≤2), and with HBV
DNA level >2000 IU/mL (where HBV DNA testing is available).

53. HIV and Hepatitis B Co-infection
The natural history of both disease is affected
HIV infection –
> accelerate HBV-related liver disease progression
> Lower rates of loss of serum hepatitis B e antigen
> Increase risk of cirrhosis, liver related mortality, and HCC at lower CD4 counts.
HBV infection –
> faster immune deterioration and higher mortality in HIV infection
> death rate two fold high with Co-infection than HIV monoinfection
> faster CD4 decline
> slower CD4 recovery following ART
> increase rate of ARV toxicity

54. Treatment of HIV and HBV Co-infected patients
Start dual therapy irrespective of CD4 count, HBV viral load or
status of liver disease e.g., ALT level or fibrosis stage
HBV and HIV co-infected adults and adolescents, tenofovir +
lamivudine + efavirenz as a fixed-dose combination is
recommended
This treatment strategy has achieved high rates of HBV DNA
suppression (90%), HBeAg loss (46%) and HBsAg loss (12%) in
HBeAg-positive patients after 5 years of treatmen

55. Hepatitis C infection
 HCV is linear, single stranded enveloped RNA virus belonging to
flavivirus family
 Infection acquired via -
infected syringes and needle
infected blood
sexual transmission specialy in MSM group
from mother to her child
 HCV causes acute and chronic hepatitis

56. Acute hepatitis is often clinically mild and marked by fluctuating elevation of serum
aminotransferase level
Chronic infection with HCV is usually clinically silent, very rarely associated with life-
threatening disease.
Spontaneous clearance of acute HCV infection occurs within six months of infection in 15–
45% of infected individuals in the absence of treatment. Almost all the remaining 55–85% of
persons will harbor HCV for the rest of their lives (if not treated) and are considered to have
chronic HCV infection.

57. Left untreated, chronic HCV infection can cause liver cirrhosis, liver failure and HCC.
Of those with chronic HCV infection, the risk of cirrhosis of the liver is 15–30%
within 20 years. The risk of HCC in persons with cirrhosis is approximately 2–4% per
year.
Extrahepatic manifestation of HCV infection
glomerulonephritis
thyroiditis
Sjogren syndrome
insulin resistance - type 2 diabetes
skin disorders such as porphyria cutanea tarda and lichen planus.

58. Laboratory diagnosis
 eclipse phase of 1-2 weeks
 Appearance of HCV RNA then HCV cor p22 Ag
 Serological window followed by Antibody response (HCVc Ag complexed with
these Antibodies specific for HCV
 Standard method of diagnosis – Anti HCV Ab
 Elevation of aminotrasferases
 Confirmation by HCV RNA detection prior to considering treatment
 Anti HCV Ab from an infected mother may persist in children(<18 month)
 HCV RNA detection also used in children (after 2 month of age)

62. Whom to Test
People who inject drugs ( PWID)
Men who have sex with men
Female sex workers
People who received blood transfusion before routine testing for
hepatitis C
People who need frequent blood transfusion, such as, thalessemic and
dialysis patients People living with HIV
Inmates of prisons and other closed settings

63. Treatment of viral Hepatitis C infection
Management of Hepatitis Naïve patient

65. Management of Treatment experienced patient

66. Drug interaction with DAA
Carbamazepin and phenytoin are contraindicated with all regimen
Sofosbuvir used with caution in patient with severe renal impairment

68. HIV HCV Co-infection
 Monitoring and consideration for fewer Drug-Drug Interactions (DDIs) between
DAAs and ARV medicines.
 first initiate treatment for HIV and achieve HIV suppression before starting HCV
treatment.
 Some circumstances where treat HCV infection firs than HIV-
 moderate-to-severe fibrosis at risk of rapid liver disease
 HIV infection is not associated with significant immunosuppression
 ART-related hepatotoxicity in the presence of HCV infection
 Highly hepatotoxic ARV drug like stavudine (d4T), didanosine (ddI), nevirapine
(NVP) or full-dose ritonavir (600 mg twice a day)not used with HCV co-infection