Journal Review

Hepatitis B
 Hepatitis B
Hepatitis B infection is a serious global healthcare problem. Often transmitted via
body fluids like blood, semen, and vaginal secretions, the hepatitis B virus can
cause liver injury. After infection with the hepatitis B virus, the majority of adults
are able to clear the infection. Patients can present with acute symptomatic
disease or have an asymptomatic disease that is identified during screening for
the hepatitis B virus. This article focuses on identifying who is at risk of hepatitis
B, and clinical evaluation and management of patients with hepatitis B by an
interdisciplinary team. It also focuses on preventive measures.
 Table of contents

01. Introduction 03. Treatment

02. Clinical Feature 04. Conclusions

01. Introduction
Introduction

Hepatitis B viral infection is a serious global healthcare problem. It is a potentially life-threatening liver infection
caused by the hepatitis B virus (HBV)

It is often transmitted via body fluids like blood, semen, and vaginal secretions. The majority (more than 95%)
of immunocompetent adults infected with HBV can clear the infection spontaneously

During the acute infection, patients can have subclinical or anicteric hepatitis, icteric hepatitis, or less commonly
fulminant hepatitis. In chronic infection, patients can have an asymptomatic carrier state, chronic hepatitis,
cirrhosis, and hepatocellular carcinoma.
Cont…

Initial symptoms are nonspecific and may include anorexia, nausea, vomiting, abdominal pain, and jaundice. In
cases of severe liver damage, patients can develop jaundice, hepatic encephalopathy, ascites, gastrointestinal
bleeding secondary to esophageal varices, coagulopathy, or infections

Diagnosis is based on serologic blood tests in patients with suspected signs and symptoms and associated risk
factors for viral hepatitis
 Epidemiology
HBV infection has the potential for progression to a chronic state and thus presents
as a global public health While hepatitis B vaccines are available, limited access
to healthcare and lack of proper health education contributes to the increasing global
prevalence of hepatitis B. Lower incidence of hepatitis B in the United States
compared to Asia and Africa is due to better access to healthcare and better use of
vaccinations and other preventive measures.

Worldwide Statistics
- 350-400 million of the world population has chronic hepatitis B
- The following population is known to have a higher prevalence: Asian
Pacific Islanders, Alaskan Eskimos, and Australian aborigines.
- The prevalence of hepatitis B is reduced after the initiation of the
hepatitis B vaccination program.
- 10 genotypes (A-J) of hepatitis B have been identified
 Epidemiology
High-risk groups for HBV infection include intravenous drug users, infants born to
infected mothers, males who have sexual intercourse with other males, hemodialysis
patients (and workers), healthcare workers, household contacts of known patients
with chronic HBV. A majority of the global HBV disease burden is primarily through
vertical transmission.
 z
Pathophysiology

Hepatitis B virus is transmitted via percutaneous inoculation or through mucosal exposure with infectious
bodily fluids and oral-fecal transmission

The incubation period of HBV infection is typically between 30 and 180 days, and while recovery is
common in immunocompetent patients, a small percentage can progress to a chronic state, serologically
defined as the presence of HBsAg for greater than six months.

The pathogenesis of liver disease in HBV infection is mainly immune-mediated, and in some

circumstances, HBV can cause direct cytotoxic injury to the liver. 
 z
Pathophysiology

HBsAg and other nucleocapsid proteins that are present on cell membranes promote T cells-induced
cellular lysis of HBV-infected cells.

Cytotoxic T cell response to HBV-infected hepatocytes is relatively ineffective; a significant majority of

HBV DNA is cleared from the hepatic system prior to maximal T cell infiltration, suggesting that the
immune response is likely more robust in the early stages of infection.

Hepatitis B-associated injury is also seen in post-liver transplant patients with hepatitis B that are on
immunosuppressant therapy. The histological pattern that follows from this infection is termed fibrosing
cholestatic hepatitis and is thought to be associated with an overwhelming exposure to HBsAg.
 Histopatology

Acute Hepatitis B Infection
• lobular disarray
• ballooning degeneration
• multiple apoptotic bodies
• Kupffer cell activation
• lymphocyte-predominant lobular and portal inflammation

• Lymphocyte-predominant portal inflammation with

Chronic Hepatitis B Infection interface hepatitis
• spotty lobular inflammation
 Clinical
02. Feature
 History and Physical

Patients infected with HBV could be asymptomatic initially and, depending on the
particular genotype, might not be symptomatic throughout the infected state

Symptomatic from acute HBV infection, manifested as fever, skin rash,

arthralgia, arthritis, onset of jaundice, abdominal pain, nausea, and anorexia.

History taking should emphasize the social history, including sexual practices (e.g., unprotected,
same-sex, etc.), illicit drug use, profession (e.g., healthcare worker, sex worker), and living
arrangements (i.e., within the same household as a patient with HBV infection)
 History and Physical

Physical examination should also assess for stigmata of chronic liver disease,
including jaundice, ascites, hepatomegaly, splenomegaly, palmar erythema,
Dupuytren contractures, spider nevi, gynecomastia, caput medusa, and hepatic
encephalopathy which suggests portal hypertension and cirrhosis.

Extrahepatic manifestations include polyarteritis nodosa and glomerular disease

(membranous nephropathy and, less often, membranoproliferative
glomerulonephritis) and anemia has also been described.
 Diagnosis

The diagnosis
of hepatitis
Presence of HBsAg
B relies on the physical The period of
rarely persists beyond 6
and evaluation of serum time between the
months after
or viral biomarkers. Viral disappearance of
infection and
serology of hepatitis B is HBsAg and
typically precedes
usually detectable 1-12 the appearance of Anti-
detectable quantities of
weeks after initial HBsAg is termed “the
the corresponding
infection with the window period” or
antibody to surface
primary viral marker “serological gap.
antigen (Anti-HBsAg)
being hepatitis B surface
antigen (HBsAg)
 Diagnosis

Immune-mediated
HBsAg is the first destruction of the Liver
virological marker to be nucleocapsid allows transaminases should
detected because  its exposure of core antigen not be a sole guide to
exposure on the viral (HBcAg) or e antigen diagnosing
surface and is indicative (HBeAg) with suspected hepatitis
of an acute infection subsequent antibody B infection.
development.
 Diagnosis

The presence of antibodies to HBsAg The persistence of serum HBsAg for a

indicates immunized status while the duration of 6 months or greater
presence of antibodies to HBeAg refers delineates acute hepatitis B infection
to a possible chronic infection state. from chronic hepatitis B infection
 Natural History

Phase 1

• Phase 1: HBeAg-positive chronic HBV infection, previously termed ‘‘immune tolerant’’ phase;
characterised by the presence of serum HBeAg, very high levels of HBV DNA and ALT
persistently within the normal range according to traditional cut-off values (upper limit of
normal (ULN) approximately 40 IU/L)
• In the liver, there is minimal or no liver necroinflammation or fibrosis but a high level of HBV
DNA integration and clonal hepatocyte expansion suggesting that hepatocarcinogenesis
• These patients are highly conta- gious due to the high levels of HBV DNA.
 Natural History

Phase 2

• HBeAg-positive chronic hepatitis B is characterised by

• the presence of serum HBeAg, high levels of HBV DNA and ele-
• vated ALT. In the liver, there is moderate or severe liver necroinflammation and accelerated
progression fibrosis
• Most patients can achieve HBeAg seroconversion and HBV DNA suppression and enter the
HBeAg-negative infection phase.
• Other patients may fail to con- trol HBV and progress to the HBeAg-negative CHB phase for
many years.
 Natural History
Phase 3

• HBeAg-negative chronic HBV infection, previously termed ‘inactive carrier’ phase, is

characterised by the presence of serum antibodies to HBeAg (anti-HBe), undetectable or
low (\2,000 IU/ml) HBV DNA levels and normal ALT according to traditional cut-off values
(ULN ~40 IU/L)

Phase 4

• HBeAg-negative chronic hepatitis B is characterised by the lack of serum HBeAg usually

with detectable anti-HBe and persistent or fluctuating moderate to high levels of serum HBV
DNA (often lower than in HBeAg-positive patients), as well as fluctuating or persistently
elevated ALT values.
 Natural History

Phase 5

• HBsAg-negative phase is characterised by serum negative HBsAg and positive antibodies to

HBcAg (anti-HBc), with or without detectable antibodies to HBsAg (anti-HBs)
• This phase is also known as ‘‘occult HBV infection”
Following groups of people should be screened for
z
Hepatitis B
- Persons born in high or intermediate endemic areas (HBsAg prevalence of greater than
or equal to 2%). African countries, countries from

- History of illicit intravenous drug use.

- Men who have sex with men.

- Persons on immunosuppressive therapy.

- Persons with elevated ALT or AST of unknown origin.

- Blood, plasma, organ, tissues, or semen donors.

- Persons with end-stage renal disease.

- All pregnant women and infants born to HBsAg-positive mothers.

- Persons with chronic liver disease and HIV.

- Close contacts of HBsAg-positive persons, such as household, sexual, or needle-

sharing.
Following groups of people should be screened for
z
Hepatitis B
- Persons with more than one sexual partner in the last six months.

- Persons requesting evaluation or treatment for sexually transmitted infections.

- Health care workers or public safety workers who are at risk for occupational exposure
to blood or blood-contaminated body fluids.

- Residents and staff at facilities for developmentally disabled persons.

- Travelers to countries with an intermediate or high prevalence of Hepatitis B virus

infection.

- 19-59-year-old persons with diabetes who have not been vaccinated for Hepatitis B.

- Persons who are the source of blood or body fluid exposures that might require post-
exposure prophylaxis
 Interpretation of Serologic Markers
z

Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B surface antigen (anti-HBs),

Hepatitis B core Ab (Anti-HBc) IgM, Hepatitis B core Ab (Anti-HBc) IgG, Hepatitis B e
antigen (HBeAg), and Hepatitis B e antibody (anti-HBe)

HBsAg: Acute infection Anti-HBs: Recovery

HBeAg: Mostly
(less than 6 months) or from acute infection or
associated with high
chronic infection (more immunity from
viral load.
than 6 months). vaccination.
 Interpretation of Serologic Markers
z

Anti-HBc IgG:
Exposure to
infection, chronic
Anti-HBc IgM:
infection (if
Acute infection,
present along
an only marker
with HBsAg), Hepatitis B viral
Anti-HBe: Low present in the
recovery from DNA is for
replicative window period,
acute infection detection of viral
phase. can be present
(if present with load.
during
anti-HBs), if
exacerbation of
isolated
chronic infection.
presence, may
represent occult
infection.
03. Treatment
 Prevention

Preventive measures constitute a major

component of the management of hepatitis B. As
of 2019, hepatitis B vaccines available in the
United States are categorized into either single-
antigen hepatitis B vaccines or combination
vaccines.
29
30
 Management

Acute hepatitis B infection is self cleared in 95% of healthy adults

Patients with severe acute and protracted acute severe disease (total bilirubin more
than 3 mg/dl or direct bilirubin more than 1.5 mg/dl, INR more than 1.5, hepatic
encephalopathy, or ascites) need antiviral treatment.

The severity of the disease is based on clinical assessment, blood counts, liver
enzymes, and liver histology
 Management
FDA-approved medications for chronic hepatitis B include interferons (peginterferon
alfa-2a, interferon alfa-2b), nucleoside analogs (entecavir, lamivudine, telbivudine),
and nucleotide analogs (adefovir, tenofovir)

Entecavir and tenofovir are preferred for acute HBV infection if treatment is warranted,
due to their relatively higher barrier to resistance.

Lamivudine was the first effective agent to successfully used to suppress viral counts
but was associated with high drug resistance
33
 Goals Antiviral Therapy

Suppression of hepatitis B virus

Reduction of liver inflammation
replication

Prevention of progression to liver

cirrhosis and hepatocellular
carcinoma
Appropriate treatment response is indicated by the
following findings:

Loss of HBsAg and

Blood tests: normalization Undetectable hepatitis B HBeAg with
of ALT viral DNA seroconversion to anti-
HBs and anti-HBe

Surgical intervention for

Reduced inflammation on hepatitis B is only
liver biopsy with no indicated for fulminant
worsening of fibrosis liver disease requiring
transplantation.
 Differential Diagnosis

Autoimmune Drug-induced liver

Alcoholic hepatitis Cirrhosis
hepatitis injury

Hemochromatosis Hepatitis A Hepatitis C Hepatitis D

Human
Hepatocellular
Hepatitis E immunodeficiency Wilson disease
carcinoma
virus
04. Conclusion
 Prognosis

Acute HBV infection can be treated symptomatically and in

immunocompetent patients, can spontaneously resolve.

Those that progress to the chronic state,

however, are at increased risk for the
development of hepatocellular
carcinoma, cirrhosis, or fulminant liver
failure.
 Complication

Chronic hepatitis B Both recurrent and “de novo”

predisposes a patient to the
development of portal
hypertension, cirrhosis, and
its complications or
hepatocellular carcinoma
(HCC).
AIH can occur post liver For refractory cases,
transplantation, and are switching azathioprine to
treated similarly, using a MMF or changing the
combination of calcineurin inhibitor has been
glucocorticoids and recommended
azathioprine.
 Reference

1. Tripathi N, Mousa OY. Hepatitis B. [Updated 2021 Jun 15]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK555945/?report=classic
2. Guidelines CP. Clinical Practice Guidelines EASL 2017 Clinical Practice
Guidelines on the management of hepatitis B virus infection q. 2017;67(0).
Thankyou