Hepatitis, Viral

Overview
Definition
Etiology
Risk Factors
Signs and
Symptoms
Differential
Diagnosis
Diagnosis
Physical
Examination
Laboratory
Tests
Imaging
Other
Diagnostic
Procedures
Treatment
Options

Treatment Strategy
Drug Therapies
Surgical Procedures
Complementary and
Alternative Therapies
Patient Monitoring
Other Considerations
Prevention
Complications/Sequelae
Prognosis
Pregnancy
References

Overview
Definition
Hepatitisinflammation of the liverrefers to a
broad range of conditions with viral, toxic
(including alcohol), pharmacologic, and immunemediated etiologies. A systemic infection,
hepatitis can be localized in the liver or be part of
a generalized process. Viral hepatitis, the most
common, can be subdivided into a number of
types.

Type A (HAV)
Type B (HBV)
Type C (HCV)

Type D (HDV) or delta hepatitis

Type E (HEV)
Non-A, non-B, non-C hepatitis (NANBNC
hepatitis)

Hepatitis also is categorized by duration.

Acute hepatitis: Less than six months

Chronic hepatitis: Longer than six months
chronic persistent hepatitis is more common
while chronic active hepatitis is more serious

HAV, HBV, and HCV, the most prevalent, affect a

half million Americans annually and millions
worldwide.

HAV, the most common, occurs both

sporadically and in epidemics (autumn and
winter), often affecting school children.
Incubation is 15 to 50 days; infectivity two to
three weeks near end of incubation. Does
not become chronic.
HBV affects all ages. Six-month incubation;
infectivity during HBsAg positivity. Can
become chronic.
HCV affects all ages. Incubation is 30 to 90
days; infectivity during anti-HCV positivity.
Can become chronic.

Etiology

HAV: 27-nm RNA virus transmitted via fecaloral and ingestion of contaminated food and
water
HBV: 42-nm DNA virus transmitted via
injection of contaminated blood/derivatives,
IV drug use, and sexual intercourse
HCV: Flavivirus-like RNA agent transmitted
via blood transfusion, IV drug use, and

possibly sexual intercourse

Viral hepatitis may also result from herpes, yellow
fever, rubella, coxsackie, and adenovirus.

Risk Factors
HAV:

Poor hygiene, unsanitary conditions

Contaminated food and water
Raw shellfish

HBV and HCV:

Transfusions
Employment as health care worker, medical
laboratory technician, dialysis technician
(needlestick)
IV drug use
Unprotected sex
Vertical transmission during pregnancy
Impaired immunity (leukemia, Down's
syndrome, dialysis patients)
Tattoos

Organ transplants

Signs and Symptoms

Symptoms range from mild to severe. Although
HAV, HBV, and HCV symptoms are similar, HBV
and HCV symptoms usually will be more severe.
Importantly, even patients with chronic active
hepatitis may be asymptomatic. (Increased
transaminase level may be the first sign.)
Symptoms include:

Jaundice (although most are anicteric)

Malaise, fatigue, anorexia

Nausea, vomiting, abdominal discomfort
Dark urine, colorless stool
Myalgia, arthralgia

Headache, fever, flu

Differential Diagnosis

Cytomegalic inclusion infection

Mononucleosis
Hepatic malignancy
Ischemic hepatitis
Leptospirosis
Drug-induced hepatitis
Alcoholic hepatitis
Extrahepatic biliary obstruction
Autoimmune hepatitis

Wilson's disease

Diagnosis
Physical Examination
Physical signs include:

Enlarged and tender liver

Enlarged spleen

Posterior cervical lymphadenopathy

Laboratory Tests
Serodiagnosis reveals the presence of
components of HBV (e.g., HBsAg) and HCV

viruses and of antibodies to HAV (IgM

antibodies), HBV (anti-HBs, anti-HBc), and HCV
(not for a number of weeks), markers that help
determine the type, severity, and status of the
condition. Urinalysis reveals bilirubin and an
increase in serum aminotransferases.
Other findings include:

Hepatocellular damage (elevated

transaminase levels)
Elevated serum alkaline phosphatase
Depressed white cell count
Signs of cirrhosis (fibrous scarring and
hepatic lobular architecture damage)
Necrosis of periportal liver cells
Lymphocytic and plasma cell infiltration
Mild transient anemia, mild hemolytic anemia
Granulocytopenia
Lymphocytosis

Increase in reticulocyte count

Imaging
Ultrasound can indicate ascites or exclude
obstruction.

Other Diagnostic Procedures

Diagnosis involves both physical assessment and
laboratory work and may require biopsy. A
detailed history can reveal risk factors as well as
previous incidences of hepatitis. Liver biopsy may
be needed to confirm chronic hepatitis (active or
persistent) and to assess disease progression.

Treatment Options
Treatment Strategy
Treatment is usually outpatient, but
hospitalization may be necessary for severe
cases. Treatment regimen depends on condition
severity and prognosis.

Acute viral hepatitis: Treat with rest,

aggressive hydration, and balanced nutrition.
Base patient activity on fatigue limits.
Mandate that patients avoid alcohol at least
until liver enzymes are normal, perhaps
longer. Use drug therapy to alleviate
symptoms.
Chronic active hepatitis: Generally treated by
hepatologist with immunomodulators
following a liver biopsy.

Drug Therapies
HAV: Immune globulin administered pre- and
postexposure, <2 weeks, at a dose of 0.02 cc/kg
intramuscular, may prevent infection.
HBV: Prophylaxis with hepatitis B immune
globulin following exposure and/or vaccine prior
to exposure may be used; the vaccine is given in
3 doses over a 7-month time course. Promising
new approaches include the second-generation
nucleoside analogs lamivudine, which seems to
be well tolerated, safe, and efficacious, and
famcyclovir. -interferon has been shown to
eliminate viral replication in 25 to 40% of patients.
Other approaches currently under evaluation

include -interferon, thymosin, and the

combination of -interferon with ursodeoxycholic
acid.
HCV: Treatment for low doses of -interferon are
used to treat chronic hepatitis C and are effective
in less than half of patients. Discontinuation of
treatment leads to a high rate of relapse.
Ribavarin used in conjunction with interferon has
shown promise in yielding a 40 to 50% response
rate, higher than with interferon alone, making
this combination the first-line therapy for suitable
patients. Ribavirin, though, does increase the
patient's toxicity profile, and is not effective when
used alone.
Sedatives can precipitate hepatic encephalopathy
and should be avoided.

Surgical Procedures
Transplantation may be necessary with fulminant
active hepatitis and end-stage liver disease.

Complementary and Alternative Therapies

Fulminant active hepatitis and end-stage liver
disease require immediate medical attention.
Alternative therapies may be hepatoprotective,
support liver function, minimize severity of the
disease, and enhance healing.

Nutrition

Reduction or elimination of alcohol, caffeine,

refined foods, sugar, food additives, and
saturated fats (meat and dairy products) may
be recommended.
Small, frequent meals are suggested to
optimize digestion and absorption, as well as
to stabilize blood sugar. Hypo- and
hyperglycemic conditions place undue strain
on the liver.
Increased intake of whole grains, fresh
vegetables, fruits, vegetable proteins
(legumes such as soy), and essential fatty
acids (cold-water fish, nuts, and seeds) may
support overall health. Foods that are
specifically supportive to liver function
include beets, artichokes, yams, onions,
garlic, green leafy vegetables, apples, and
lemons.
Green tea is a powerful antioxidant and
contains flavonoids that decrease
inflammation. 2 to 3 cups/day may be
recommended. Decaffeinated should be
used, or caution exercised with caffeinated
form. Green tea is also a good source of
vitamin K see below for additional
information.
Acidophilus supplements (one capsule with
meals) help normalize bowel flora. Vitamin K
is synthesized by these beneficial bacteria
and is essential for normal clotting activities
of the liver. Vitamin K levels are often low in
hepatitis and may be supplemented, 100 to
500 mg/day. Dark leafy green vegetables are
high in vitamin K.
Vitamin C (1000 to 1500 mg/day), betacarotene (100,000 IU/day), vitamin E (400 to
800 IU/day), and zinc (30 to 50 mg/day)
enhance immunity. B-complex (50 to 100
mg/day), especially folic acid (800 to 1000
mcg/day) and B12 (1000 mcg/day), are

thought to be hepatoprotective and optimize

liver function.
Selenium (200 mcg/day) is useful for liver
detoxification and fatty acid metabolism.
Dessicated liver and thymus extracts may be
considered to improve liver regeneration and
immune function.
Glutathione (500 mg bid) or N-acetylcysteine
(200 mg bid to tid, a precursor to glutathione)
provide detoxification and antioxidant
support.
Consider lecithin, choline, and methionine to
support fat metabolism.

Herbs
Herbs are generally a safe way to strengthen and
tone the body's systems. As with any therapy, it is
important to ascertain a diagnosis before
pursuing treatment. Herbs may be used as dried
extracts (capsules, powders, teas), glycerites
(glycerine extracts), or tinctures (alcohol
extracts). Unless otherwise indicated, teas should
be made with 1 tsp. herb per cup of hot water.
Steep covered 5 to 10 minutes for leaf or flowers,
and 10 to 20 minutes for roots. Drink 2 to 4
cups/day. Tinctures may be used singly or in
combination as noted.
Many herbs have powerful liver-protective
properties, aiding in detoxification and promoting
bile production and flow, as well as nourishing
and repairing liver tissue. For best results, three
to four liver-supportive herbs should be combined
with two to three antiviral and immune-stimulating
herbs. The herbal treatment of hepatitis can be
complicated and should be administered under
physician supervision. Choice of herbs is
dependent on disease state and presentation of

pathology. The high doses of single herbs

suggested may be best administered via dried
extracts (encapsulated), although tinctures (60
drops qid) and teas (4 to 6 cups/day) may also be
used.
Herbs for liver support:

Milk thistle (Silybum marianum, 200 to 250

mg tid) protects the liver parenchyma and
may prevent necrotic changes. May also be
used as phosphatidylcholine-bound silymarin
(100 to 150 mg tid), which is more specific
for hepatitis infections.
Chinese thoroughwax (Bupleurum falcatum)
contains steroid-like molecules that are
potent anti-inflammatories. May induce
nausea in sensitive individuals; decrease
dose to ameliorate side effect. (Please note
that while glucocorticoids are used
occasionally for viral hepatitis, there is a
great deal of controversy about their use
particularly for HBV and HCV; so, Bupleurum
falcatum should be used with particular
caution.)
Globe artichoke (Cynara scolymus) promotes
liver regeneration.
Schizandra berry (Schizandra chinensis) is
hepatoprotective and promotes liver
regeneration and detoxification.
Eclipta alba inhibits hepatitis B replication
and is usually used with phyllanthus.
Phyllanthus amarus (200 mg tid) is an
ayurvedic herb shown to inhibit hepatitis B
replication. Long-term use of a year or more
may be necessary for optimum effectiveness.
Turmeric (Curcuma longa, 250 to 500 mg tid)
is a potent anti-inflammatory herb that is also
hepatoprotective. Combine with bromelain
(250 to 500 mg tid between meals), a
proteolytic enzyme, to potentiate effects.

Immune support and antivirals:

Licorice root (Glycyrrhiza glabra, 250 to 500

mg tid), particularly its extract, glycyrrhizin, is
hepatoprotective. Concurrent administration
of glycine and cysteine appear to modulate
glycyrrhizin's actions and prevent its
aldosterone-like action.
Astragalus root (Astragalus membranaceus)
augments natural killer cell activity and
interferon response and promotes liver
detoxification.
Coneflower (Echinacea purpurea) is an
antiviral and immune-stimulating herb best
used during acute infection.
Goldenseal (Hydrastis canadensis) has
antimicrobial and immune-stimulating
properties, and also enhances liver function.

Homeopathy
An experienced homeopath should assess
individual constitutional types and severity of
disease to select the correct remedy and potency.

Acupuncture
May be beneficial in modulating immune function
and supporting liver function.

Massage

Therapeutic massage may be helpful in reducing

the effects of stress, which inhibits immune
function.

Patient Monitoring

Although patient isolation usually is not

required during treatment, strict attention to
hygiene is. Food handlers should be
extremely cautious in the case of HAV.
Healthcare workers should always exercise
universal precautions to avoid contraction or
transmission of HBV or HCV.
Monitor patients at one- to three-week
intervals; normal activities can resume when
symptoms disappear and laboratory tests are
normal. HBV patients with detectable surface
antigen at six months should be managed
with a hepatologist.
Patients with chronic persistent hepatitis may
require a follow-up liver biopsy after two to
three years to confirm the diagnosis.

Other Considerations
Prevention

HAV: Attention to hygiene and immune

serum globulin; hepatitis A vaccine
HBV: Attention to hygiene, blood-product
screening, proper needle use/disposal, safesex practices, hepatitis B immune globulin,
vaccine
HCV: Attention to hygiene, blood-product

screening, proper needle use/disposal, safesex practices, and possibly immune serum
globulin

Complications/Sequelae

Posthepatitis syndrome
Cholestatic hepatitis
Fulminant hepatitis (necrosis)
Chronic hepatitis
Cirrhosis

Hepatocellular carcinoma

Prognosis
Acute:

Self-limiting, generally resolves in one to

three months
Suspect chronic active liver disease after 12
weeks
In rare cases, progresses to necrosis and
possibly death in less than six months

Chronic:

Persists for longer than six months

Chronic persistent hepatitis is benign,
generally asymptomatic, seldom results in
cirrhosis, and generally resolves without
progressing.
Chronic active hepatitis can result in cirrhosis
and liver failure.

Jaundice, if present, usually disappears in two to

eight weeks. Fulminant hepatitis (more common
in HBV) is the primary cause of death.

Morbidity and mortality are higher with HBV and

HCV:

HAV: Seldom fatal, but requires up to 30

days bed rest. Could recur after 90 days.
HBV: Patients sometimes become
asymptomatic carriers. Frequently slow to
resolve, thus a common cause of chronic
liver disease and cirrhosis.
HCV: Virus remains in the blood for many
years, thus a common cause of liver failure,
liver cancer, and cirrhosis.

Pregnancy
Active viral hepatitis can be a serious
complication in pregnancy. The safety of herbs in
pregnancy has not been adequately investigated.
Milk thistle (1 cup of tea tid) is safe to use as
maintenance. Other herbs and high doses of
vitamins should be used only under the
supervision of a qualified practitioner.

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