Hepatitis B

Hepatitis B (HBV) 

Introduction

Hepatitis B is a DNA virus infection affecting the liver and remains one of the leading causes of:

• Chronic hepatitis
• Liver cirrhosis
• Hepatocellular carcinoma (HCC)
• Liver failure
• Need for liver transplantation

HBV infection may present as:

• Acute hepatitis
• Chronic hepatitis
• Fulminant hepatic failure
• Inactive carrier state
• Occult infection

Virus Characteristics

Component	Function
Surface antigen (HBsAg)	Envelope protein
Core antigen (HBcAg)	Nucleocapsid
e antigen (HBeAg)	Marker of active replication
DNA polymerase	Reverse transcriptase activity
Covalently closed circular DNA (cccDNA)	Persistent nuclear template

Routes

Route	Examples
Perinatal	Mother to child
Sexual	Unprotected intercourse
Parenteral	IV drug use, transfusion
Household	Razors, toothbrushes
Occupational	Needle-stick injury

Risk Factors

High-Risk Group	Risk
IV drug users	Very high
MSM	High
Hemodialysis patients	High
Healthcare workers	Occupational exposure
HIV patients	Coinfection
Infants born to HBsAg-positive mothers	Perinatal transmission

Pathogenesis

HBV itself is not directly cytopathic.

Liver injury occurs due to:

• Host immune response
• Cytotoxic T-cell attack on infected hepatocytes

Natural History

Acute Infection Outcomes

Outcome	Adults	Neonates
Recovery	90–95%	<10%
Chronic infection	<5%	>90%

Clinical Features

Incubation Period-Usually 1–4 months.

Symptoms

Constitutional	Hepatic
Fever	Jaundice
Malaise	RUQ pain
Fatigue	Dark urine
Anorexia	Hepatomegaly
Arthralgia	Nausea/vomiting

Extrahepatic Manifestations

Immune-complex mediated.

Manifestation	Mechanism
Polyarteritis nodosa	Vasculitis
Membranous nephropathy	Immune complex
Cryoglobulinemia	Immune activation
Arthritis	Immune mediated

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.

Fulminant Hepatitis B

Severe acute liver failure characterized by:

• Coagulopathy
• Encephalopathy  jaundice, ascites, gastrointestinal bleeding secondary to esophageal varices,or infections
• Massive hepatic necrosis

Chronic Hepatitis B

while recovery is common in immunocompetent patients, a small percentage can progress to a chronic state defined as Persistence of HBsAg for ≥6 months.Evidence of ongoing HBV infection with or without hepatic inflammation

Occult HBV Infection

Defined as:

• HBV DNA positive
• HBsAg negative

Seen in:

• Immunosuppression
• HCC
• Cryptogenic liver disease

Differential Diagnosis

Condition	Distinguishing Feature
Hepatitis A	Acute only
Hepatitis C	High chronicity
Alcoholic hepatitis	AST>ALT
Autoimmune hepatitis	ANA/SMA positive
Drug-induced liver injury	Drug exposure history

Laboratory Diagnosis

Liver Function Tests

Test	Finding
AST/ALT	Elevated in later phase, could be normal
Bilirubin	Elevated
INR	Severe disease marker
Albumin	Low in chronic liver disease

HBV Serology

This is the most important topic clinically and for exams.

Marker	Meaning
HBsAg	Current infection,first virological marker to be detected
Anti-HBs	Immunity
Anti-HBc IgM	Acute infection
Anti-HBc IgG	Past exposure
HBeAg	Active replication
Anti-HBe	Lower infectivity,possible chronic infection state.
HBV DNA	Best marker of:Viral replication and Treatment response,High HBV DNA alone does not automatically mean treatment is needed.

Interpretation of Serology

HBsAg	Anti-HBs	Anti-HBc	Interpretation
–	+	–	Vaccinated
–	+	+	Past infection
+	–	IgM +	Acute infection
+	–	IgG +	Chronic infection
–	–	Anti-HBc only	Window period/occult infection

Window Period-The period of time between the disappearance of HBsAg and the appearance of Anti-HBsAg is termed “the window period” or “serological gap.” During the window period, other viral serology could also be undetectable.The only reliable serologic marker is IgM anti-HBc.

Seroconversion- refers to the transition between an acute, immune-active phase to an inactive carrier state and is marked by the spontaneous development of antibodies to HBeAg.

Imaging

Ultrasound Abdomen

Assesses:Cirrhosis/Portal hypertension/Splenomegaly/HCC screening

Elastography

Assesses fibrosis noninvasively.

Examples:FibroScan

Score	Formula Components
APRI	AST + platelet
FIB-4	Age, AST, ALT, platelets

Liver Biopsy

Not always required.

Indications:

• Uncertain fibrosis stage
• Discordant tests
• Research settings

Histopathology

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

Chronic Hepatitis B Infection: Lymphocyte-predominant portal inflammation with interface hepatitis and spotty lobular inflammation.

Complications

Complication	Details
Cirrhosis	Progressive fibrosis
Portal hypertension	Varices, ascites
HCC	Can occur without cirrhosis
Liver failure	End-stage disease
HBV reactivation	Immunosuppression

Hepatocellular Carcinoma (HCC)

HBV is oncogenic due to:

• Chronic inflammation
• DNA integration
• Cirrhosis

HCC Surveillance

Every 6 months:

• Ultrasound
  ± AFP

High-risk groups:

• Cirrhosis
• Asian men >40
• Asian women >50
• Africans >20
• Family history HCC

Treatment of Acute HBV

90–95% of healthy adults recover spontaneously Therefore: Most patients require supportive care only,Antiviral therapy is reserved for selected severe cases

Severity Category	Clinical/Laboratory Features	Management
Mild Acute Hepatitis B	• Fatigue  • Nausea  • Mild jaundice  • ALT elevation  • INR normal	• Outpatient care  • Supportive treatment only
Severe Acute Hepatitis B	A.Two  or more of the following:  • INR ≥1.5  • Bilirubin >10 mg/dL  • Encephalopathy   B.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.	• Hospitalization  • Consider antiviral therapy
Acute Liver Failure (ALF) due to Hepatitis B	Acute hepatitis with:  • INR ≥1.5  • Hepatic encephalopathy  • No prior cirrhosis	• Medical emergency  • ICU admission  • Antiviral therapy  • Early liver transplant evaluation

Supportive Care

• Hydration
• Nutrition
• Avoid hepatotoxic drugs
• Avoid alcohol

Symptomatic Treatment

Nausea/Vomiting

Drug	Dose
Ondansetron	4–8 mg PO/IV
Metoclopramide	10 mg

Pruritus (Cholestatic Hepatitis)

Drug	Dose
Cholestyramine	4 g 1–4 times/day
Hydroxyzine	Symptomatic relief

Fever/Pain

• Preferred-Low-dose Paracetamol cautiously
• Avoid-NSAIDs in severe disease

Antiviral Therapy in Acute HBV Indicated only in:

•  Acute liver failure                         
•  Severe acute hepatitis B                    
•  Protracted severe disease                   
•  Immunocompromised patients (selected cases) 

Preferred:Tenofovir/Entecavir

Drug	Preferred?	Comments
Tenofovir disoproxil fumarate (TDF)	Yes(300 mg daily)	Potent
Tenofovir alafenamide (TAF)	Yes(25 mg daily)	Less renal/bone toxicity
Entecavir	Yes(0.5 mg daily)	Excellent resistance profile,Less renal/bone toxicity

Monitoring During Therapy

Parameter	Frequency
ALT	Every 3–6 months
HBV DNA	Every 3–6 months
Creatinine	Especially with TDF
HBeAg	Seroconversion
HBsAg	Functional cure assessment

Treatment Endpoints

Ideal Endpoint-HBsAg loss ± anti-HBs appearance.

Practical Endpoint-Long-term HBV DNA suppression.

Functional Cure vs Sterilizing Cure

Type	Definition
Functional cure	HBsAg loss
Sterilizing cure	Elimination of cccDNA

Current therapies rarely achieve sterilizing cure.

Chronic hepatitis B-Traditionally, antiviral therapy is not routinely recommended for patients in the immune-tolerant phase of chronic hepatitis B because these patients typically have:

• HBsAg positive
• HBeAg positive
• Very high HBV DNA levels (often >10⁶–10⁷ IU/mL)
• Persistently normal ALT
• Minimal or no hepatic inflammation/fibrosis on liver biopsy or noninvasive assessment

The rationale is that:

• Liver injury is minimal despite high viral replication.
• Response rates to antiviral therapy are relatively low.
• Long-term treatment may be required without clear clinical benefit.
• Drug resistance and cost are concerns (especially with older agents).

However, recent guidelines have become more nuanced

Current recommendations from organizations such as the American Association for the Study of Liver Diseases, European Association for the Study of the Liver, and Asian Pacific Association for the Study of the Liver suggest considering treatment in selected immune-tolerant patients, particularly when:

Consider Treatment If	Reason
Age >30–40 years	Risk of significant fibrosis despite normal ALT
Family history of HCC or cirrhosis	Higher long-term risk
Significant fibrosis on FibroScan/biopsy	Evidence of ongoing liver damage
ALT becomes elevated	Transition to immune-active phase
Extrahepatic manifestations	May benefit from viral suppression

References

1. Harrison’s Principles of Internal Medicine, 22nd ed.
2. EASL HBV Guideline 2025.
3. WHO HBV Guideline 2024.