Notes

Hepatitis B

CHB: Duration > 6mths. HBV-DNA: Negative to several billions. HBeAg positive (usually higher HBV) or negative (usually lower HBV).
Immune Tolerant CHB
Immune Active CHB
Inactive CHB

Alpha-Interferon: Zevinex Inj. (Interferon Alpha-2b) - Zudus Rs. 450/inj
PegInterferon Alfa-2B (80mcg/0.5ml) Rs. 7000 - Zydus Heptiza
Lamividine :
Tenofovir - Tenvir 300mg OD (Cipla), TenoHep (Zydus) Rs.1000/mth, Reviro (Dr. Reddys)
Entecavir (Baraclude) - Bristol-Myers Squibb, EnteHep 0.5 & 1mg (Zydus - Rs. 1800/mth)
Adefovir dipivoxil : in Lamividine Resist. cases.
Telbivudine - TelbiHep (zydus) 400mg

Natural Hx

Phase-1: HbeAg positive Chronic Infection (e+CHBI). High viral replication, but low liver injury
Phase-2: HBeAg positive CHB (e+CHB). Immune active/reactive phase. High Level of viral replication. High ALT. Risk of cirrhosis or HCC.
Phase-3: HBeAg Negative Chronic Infection. (e-CHBI). Inactive Carrier phase. Anti-HBe (seroconversion). HBV-DNA decreases < 2000. Almost normal ALT.
Phase-4: HBeAg negative CHB (e-CHB). HBV-DNA high >2000, ALT high (mod. inflamation). Immune Reactivation. Risk of cirrhosis / HCC.
Phase-5: HBeAg negative chronic infection/occult (s-CHBIo / Occult HBV infection). HBsAg nega, but anti-HBc positive. ALT, HBV-DNA may be normal. Bec. of S-region mutation. Reactivation a risk.

Immunological Markers :

FIRST MARKERS : HBsAg
Markers of Active Replication (HBeAg, HBV DNA) detectable 6wks after inoculation & prior to Symp.
MARKER with Onset of Symp.: IgM anti-HBc.(persists for many mths).
LAST MARKER : Anti-HBs is last to become positive - Marker of Resolving Infection.
HBsAg : Confirms Infection, but does not distinguish betwenn Ac. & Chr.
HBeAg : indicates ongoing Replication & Infectivity. Detection after 2 mths indicate : Chr.Inf.
Anti-Hbc IgM positivity : indicates Ac.Inf.; Negative : indicates - Chr.Inf. or indicates Reactivation of Chr.Hepatitis.
Anti-Hbs : to detect Prior Infection or Immunization.
Anti-HBe : resolution of active replication.

Tests:

1. anti-HBc (IgM) - (Hepatitis-B Core Antibody) if + -> wait for 6 mths; if Neg -> HBeAg, & HBV DNA
3. HBeAg - (Hepatitis-Be Antigen)
4. HBV-DNA (Viral-load)
Treatment of patients with HBeAg negative CHB: (1) If ALT is > 2 ULN, and HBV DNA is > 2000 IU/mL, treatment should be considered.

Dugs:

Drug Dose in Adults Use in Children Pregnancy Category Side Effects Monitoring on Treatment

Preffered

Peg-IFN-a-2a (adult) IFN-a-2b (children) 180 mcg weekly 1yr+ dose: 6 million IU/m2 three times weekly C Flu-like symptoms, fatigue, mood disturbances, cytopenia, autoimmune disorders in adults, anorexia and weight loss in children CBC (1-3 mthly), TSH (every 3 months) Clinical monitoring for autoimmune, ischemic, neuropsychiatric, and infectious complications

Entecavir 0.5 mg OD 2yr+ dose: weight-based to 10-30 kg; above 30 kg: 0.5 mg daily C Lactic acidosis (decompensated cirrhosis only) Lactic acid levels if there is clinical concern Test for HIV before treatment initiation

Tenofovir dipovoxil fumarate 300 mg OD 12 yrs + B Nephropathy, Fanconi syndrome, osteomalacia, lactic acidosis Creatinine clearance at baseline If at risk for renal impairment, creatinine clearance, serum phosphate, urine glucose, and protein at least annually Consider bone density study at baseline and during treatment in patients with history of fracture or risks for osteopenia Lactic acid levels if there is clinical concern Test for HIV before treatment initiation

Tenofovir alafenamide 25 mg OD - insufficient human data Lactic acidosis Lactic acid levels if clinical concern Assess serum creatinine, serum phosphorus, creatinine clearance, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate Test for HIV before treatment initiation

Non-Preffered

Lamivudine 100 mg OD 2 yrs+ dose: 3 mg/kg daily to max 100 mg C Pancreatitis, Lactic acidosis Amylase if symptoms are present Lactic acid levels if there is clinical concern

Adefovir 10 mg OD 12 yrs+ C Acute renal failure, Fanconi syndrome, Lactic acidosis Cr. Clearance

Telbivudine 600 mg OD - B Creatine kinase elevation, myopathy, Peripheral neuropathy, Lactic acidosis CK, Lactic Acid

Drug	Dose in Adults	Use in Children	Pregnancy Category	Side Effects	Monitoring on Treatment
Preffered
Peg-IFN-a-2a (adult) IFN-a-2b (children)	180 mcg weekly	1yr+ dose: 6 million IU/m2 three times weekly	C	Flu-like symptoms, fatigue, mood disturbances, cytopenia, autoimmune disorders in adults, anorexia and weight loss in children	CBC (1-3 mthly), TSH (every 3 months) Clinical monitoring for autoimmune, ischemic, neuropsychiatric, and infectious complications
Entecavir	0.5 mg OD	2yr+ dose: weight-based to 10-30 kg; above 30 kg: 0.5 mg daily	C	Lactic acidosis (decompensated cirrhosis only)	Lactic acid levels if there is clinical concern Test for HIV before treatment initiation
Tenofovir dipovoxil fumarate	300 mg OD	12 yrs +	B	Nephropathy, Fanconi syndrome, osteomalacia, lactic acidosis	Creatinine clearance at baseline If at risk for renal impairment, creatinine clearance, serum phosphate, urine glucose, and protein at least annually Consider bone density study at baseline and during treatment in patients with history of fracture or risks for osteopenia Lactic acid levels if there is clinical concern Test for HIV before treatment initiation
Tenofovir alafenamide	25 mg OD	-	insufficient human data	Lactic acidosis	Lactic acid levels if clinical concern Assess serum creatinine, serum phosphorus, creatinine clearance, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate Test for HIV before treatment initiation
Non-Preffered
Lamivudine	100 mg OD	2 yrs+ dose: 3 mg/kg daily to max 100 mg	C	Pancreatitis, Lactic acidosis	Amylase if symptoms are present Lactic acid levels if there is clinical concern
Adefovir	10 mg OD	12 yrs+	C	Acute renal failure, Fanconi syndrome, Lactic acidosis	Cr. Clearance
Telbivudine	600 mg OD	-	B	Creatine kinase elevation, myopathy, Peripheral neuropathy, Lactic acidosis	CK, Lactic Acid

Treatment Algorithm for HBsAg positive cases

HBeAg ALT HBV-DNA To Do

Positive <35 >20k Watch: ALT, HBV-DNA 6mthly & HBeAg Yrly

<20k Watch: Yrly

Bet 35-70 > 20k Watch: If elevation persists & age > 40 then TREAT

2k - 20k Watch: every 1-3mths, if persists for 6mths then TREAT

<2k Watch yrly

>70 >20k TREAT

2k - 20k Watch: every 1-3mths, if persists for 6mths then TREAT

<2k Watch yrly

Negative <35 >2k Watch: ALT, HBV-DNA 3mthly for 1yr & then 6mthly

<2k Watch every 6mth-1yrly

Bet 35-70 > 2k Watch: If elevation persists & age > 40 then TREAT

<2k Watch every 6mth-1yrly

>70 >2k TREAT

<2k Watch every 6mth-1yrly

HBeAg	ALT	HBV-DNA	To Do
Positive	<35	>20k	Watch: ALT, HBV-DNA 6mthly & HBeAg Yrly
	<35	<20k	Watch: Yrly
	Bet 35-70	> 20k	Watch: If elevation persists & age > 40 then TREAT
		2k - 20k	Watch: every 1-3mths, if persists for 6mths then TREAT
		<2k	Watch yrly
	>70	>20k	TREAT
		2k - 20k	Watch: every 1-3mths, if persists for 6mths then TREAT
		<2k	Watch yrly
Negative	<35	>2k	Watch: ALT, HBV-DNA 3mthly for 1yr & then 6mthly
	<35	<2k	Watch every 6mth-1yrly
	Bet 35-70	> 2k	Watch: If elevation persists & age > 40 then TREAT
	Bet 35-70	<2k	Watch every 6mth-1yrly
	>70	>2k	TREAT
	>70	<2k	Watch every 6mth-1yrly