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Liver Diseases - Management

Preventive measures - immunisation

– active iummunisation by vaccinatio
– passive immunisation

Disease modifying therapy

hepatitis B & C : alpha interferons, lamivudine
Chronic active hepatitis :immunosuppressives -
prednisolone, azathioprine
– active iummunisation by vaccination
Hep A (Havrix®),
Hep B (Engerix B®, H-B-vax II®),
Hep A, Hep B (Twinrix®)
– passive immunisation
pooled serum (high Ig titres) (HBIG)

Havrix active in 2 weeks, lasts about 1 year

Vaccine Type of Route Primary Booster2
Agent of Adm. Immunization

Hepatitis A Inactiva Intramus One dose (administer At 6–12 months

ted cular at least 2–4 weeks for long-term
virus before travel to immunity
endemic areas)
Hepatitis Inactive Intramus Three doses at 0, 1, Not routinely
B viral cular and 6 months recommended
Vaccine indication
Hepatitis A
Hepatitis B
1. Travelers to hepatitis A endemic
areas 1. For all infants
2. Homosexual and bisexual men 2. Preadolescents,
3. Illicit drug users adolescents, and young
4. Chronic liver disease or clotting
factor disorders adults
5. Persons with occupational risk for 3. Persons with
infection occupational, lifestyle, or
6. Persons living in, or relocating to, environmental risk
endemic areas
7. Household and sexual contacts of 4. Hemophiliacs
individuals with acute hepatitis A 5. Hemodialysis patients
6. Postexposure
Lamivudine (cytosine analog)
Antiretroviral Agent, Reverse Transcriptase Inhibitor

inhibits RNA- and DNA-dependent DNA polymerase
activities of reverse transcriptase.

The monophosphate form of lamivudine is incorporated

into the viral DNA by hepatitis B virus polymerase,
resulting in DNA chain termination.
Absorption : Rapid
Distribution(Vd) : 1.3 L/kg
Protein binding : <36%
Metabolism : 5.6% to trans-sulfoxide metabolite
Children : 66%
Adults : 87%
Cpmax decreased with food although AUC not
significantly affected
Half-life elimination: Children: 2 hours;
Adults: 5-7 hours
Excretion: Primarily urine (as unchanged drug)
Lamivudine (3TC® - GW)
– reverse transcriptase inhibitor
– used also in AIDS/HIV (150mg BID)
– dose in hepatitis is 100mg daily (Zeffix®)
– can be quite effective
suppresses HBV DNA
reduces progression to fibrosis
sustains normalisation of ALT
sustains HBeAg seroconversion
how long do we take it for? - recurrence of
hepatitis on cessation?
Lamivudin DOSING:
Oral: 100 mg/day
Oral: Children 2-17 years: 3 mg/kg once daily
(maximum: 100 mg/day)

Central nervous system: Headache, fatigue
Gastrointestinal: Nausea, diarrhea, vomiting, pancreatitis
Neuromuscular & skeletal: Peripheral neuropathy,
paresthesia, musculoskeletal pain
Mechanism of action
works by blocking reverse transcriptase,
an enzyme that is crucial for the hepatitis B virus
(HBV) to reproduce in the body.
approved for the treatment of
chronic hepatitis B in adults with active viral replication
persistent elevations in serum aminotransferases
(primarily ALT) or histologically active disease.
Interferons (IFN)
glycoproteins released from virus-infected cells.

In neighboring cells, interferon stimulates the production

of “antiviral proteins.” (elF2)

eIF2 reduced viral ability to initiate translation, the

production of proteins coded by cellular mRNA.

These inhibit the synthesis of viral proteins by (preferential)

destruction of viral DNA or by suppressing its translation
Interferon alfa-2a

Induction of gene transcription.
Inhibits cellular growth, alters the state of cellular
differentiation, interferes with oncogene
expression, alters cell surface antigen
expression, increases phagocytic activity of
macrophages, and augments cytotoxicity of
lymphocytes for target cells
Interferons (alpha-2a (Roferon-A®) or alpha 2-b (Intron-A®))
– chronic HCV and HBV
– use alpha-2b (more clinical experience)
– SC or IM (about 3-5 MIU 3 times a week)
– approx 50% effectiveness
– early side effects - influenza-like
use paracetamol
– late SE’s
BM suppression, thrombocytopaenia,
worsening of influenza-like syndrome
Distribution: Vd: 0.223-0.748 L/kg

Metabolism: Primarily renal; filtered through glomeruli

and undergoes rapid proteolytic degradation during
tubular reabsorption

Bioavailability: I.M.: 83%; SubQ: 90%

Half-life elimination: IV: 3.7- 8.5 hours (mean ~5 hours)

Time to peak, serum: I.M., SubQ: ~ 6 - 8 hours


up to 92%
Flu-like symptoms are common

Cardiovascular: Chest pain , edema , hypertension
Central nervous system: Psychiatric disturbances
Dermatologic: Rash, alopecia, pruritus, dry skin
Endocrine & metabolic: Hypocalcemia, hyperglycemia,
transaminases increased ,alkaline phosphatase
increased (48%)
Portal hypertension

oesophageal varices Haemorhage

stop bleeding and maintain circulation

– surgical
– vasoconstriction to blood flow e.g.
vasopressin, terlipressin
somatostatin (octreotide)
– sclerotherapy
1% sodium tetradecylsulphate, oleates
 peptide analogue of somatostatin
 causes splanchnic vasoconstriction by direct
effect on vascular smooth muscle

Octreotide infusion
(50-100 mcg bolus and 25 - 50 mcg/hr gtt)
should be started in patients with suspected or
known liver disease and UGI bleeding

Should be continued for 5-7 days total

– accumulation of nitrogenous compounds
absorbed from gut of impaired liver function
– may alter metabolism of neurotransmitters
– patient becomes drowsy and maybe
comatose (Grades I - IV)
– may have ”foetor hepaticus”
– precipitating factors
Infection , fluid depletion ,electrolyte imbalance
CNS depressant drugs, GI bleed

– Diet - protein restriction, branched chain

amino acids
– Gut sterilisation
– Laxatives - lactulose

- Metronidazole , Neomycin
– non absorbable (although some is)
oral and rectal
2 - 4g per day - care nephrotoxicity!!
disaccharide  lactic and acetic acid - prevents
absorption of ammonia by changing pH
– also acts as osmotic laxative
– dose is about 40 - 80ml per day
Gallstones Epidemiology

 80% : cholesterol stones  20 % : pigment / calcified

 Major risk factor stones.
Obesity  Calcium-bilirubinate major
Female sex hormones risk factors:
Bile acid malabsorption Chronic hemolysis
High calorie diet Alcoholic cirrhosis
Demographic Biliary infection
characteristics: Age
Northern European, Demographic characteristics:
North and South America, Far East > West,
American Indians, rural > urban
family history
Pathophysiology of Cholesterol Gallstones

Genetic or metabolic predisposition

Supersaturation of bile with cholesterol
(hepatobiliary cholesterol vs. bile acids or lecithin)
Nucleation and crystal growth
Development of macroscopic stones (poor
gallbladder emptying)
Treatment depends upon presence of symptoms, likelihood of complications, morbidity of
complications (or treatment) and cost

Treatment options currently available in U.S.:

1) Cholecystectomy (routine vs laparoscopic)

2) Gallstone dissolution with bile acids (slow dissolution)

Chenodeoxycholic acid (CDC or Chenodiol)
Ursodeoxycholic acid (UDC or Ursodiol)
3) Contact dissolution
Methyl tert-butyl ether (MTBE)
Monooctanoin (common bile duct stones)

4) Extracorporeal shock wave (lithotripsy) (ECS)

Gallstone dissolution with bile acids
(Chenodiol, Ursodiol)

Bile acid dissolution is useful only for cholesterol

CDC and UDC act by:
a) Depressing secretion of cholesterol into bile
(low cholesterol-solubility capacity due to
hydrophilic property) - Major effect

b) Expands the bile acid pool and increases bile

acid secretion - Minor effect
Chenodiol (CDC)
Approved by FDA in 1983
Criteria for treatment:
cholesterol stones, small stones,
functioning gallbladder , thin patient
Contraindications for treatment:
pigment stones, calcified stones, large (> 1.5 cm)
stones, liver disease, pregnancy
 Optimal dosage and duration:
15 mg/kg day for up to two years.
13.5% complete dissolution at two years,
40% partial dissolution at two years;
Chenodiol (CDC)

Recurrence rate of 10%/yr

low dose CDC does not prevent recurrence.
Predictors of successful dissolution:
floating stones on OCG; less than 3 stones;
less than 1.5 cm diameter; high plasma cholesterol;
weight < 100% of ideal body weight
Complete dissolution in ideal setting: 60-90%
diarrhea (33%); increased plasma cholesterol by
20 mg/dl; increased liver enzyme (AST)
Ursodiol (UDC)

Approved by FDA in 1988

Criteria for treatment and efficacy: same as CDC
Optimal dosage and duration: 10-13 mg/kg/day
no hepatotoxicity; no alteration in plasma cholesterol;
no diarrhea.
Stone recurrence may be prevented with low dose UDC
Ursodiol has replaced CDC as bile acid of choice for
gallstone dissolution
Combination CDC-UDC regimens have been used with
comparable safety to UDC alone