Viral Hepatitis

Hepatitis A

Medications (Drugs, Medicines)

Drug(s) of Choice

Antiviral therapy not indicated in acute HAV infections as spontaneous resolution occurs in almost all patients

Contraindications: Corticosteroids may add to morbidity/increased mortality.

Precautions: N/A

Significant possible interactions: Refer to manufacturer’s profile of each drug

Alternative Drugs

N/A

Patient Monitoring

• Serial measurement of serum AST/ALT
• Appropriate serum viral markers useful for evaluation of recovery or progression
• Liver biopsies in acute cases if diagnosis remains in doubt
• Monitor for metabolic complications

Prevention / Avoidance

• Good sanitation, hygiene
• Immune globulin (passive immunization): 0.02 mL/kg M (given 1-2weeks after exposure prevents illness in 80-90%). With prolonged exposure give q 5 months. Also use for close contacts, day care staff/children (if case occurs), institutions with multiple cases, travelers to areas of high prevalence (with 3 week lead time, use vaccine).
• Hepatitis A vaccine (Havrix, Vaqta):0.5mLdoselM in children > 2yrs; 1 mL in adults IM; 2nd dose 6-12 mo later for >8 yrs. Separate syringe site from immune globulin. Use for travelers, day-care staff/children, custodial facility employees, sewage workers, military, homosexual men, food handlers, Native Americans, Alaskan natives.

Possible Complications

• Icteric disease
• 3 rare variants: relapsing, cholestatic, fulminant

Expected Course / Prognosis

• Mild disease usual, often no jaundice
• No chronic liver disease
• Mortality <1%
• Lifetime immunity usual with recovery

Miscellaneous

Associated Conditions

• Arthritis
• Urticaria
• Immune complex nephritis (particularly membranous glomerulopathy)
• Anemias (including aplastic anemia)

Age-Related Factors

Pediatric: Milder; usually anicteric; may be unrecognized

Geriatric: N/A

Pregnancy

N/A

International Classification of Diseases

070 Viral hepatitis

See Also

Hepatitis B
Hepatitis C
Immunizations

Hepatitis B

Description of Medical Condition

A systemic viral infection primarily involving the liver

System(s) affected: Gastrointestinal

Genetics: Some predisposition to immunologic manifestations; DR4 — positive increase with concurrent immunologic disease

Incidence/Prevalence in USA:

• 140,000-320,000 infections/year
• 1-1.25 million chronically infected
• Post-transfusion hepatitis B (rare)

Predominant age: All ages

Predominant sex: Fulminant HBV: Male > Female (2:1)

Medical Symptoms and Signs of Disease

• Fever (60%)
• Malaise (67%)
• Nausea and vomiting
• Anorexia (54%)
• Jaundice (in adults, 62%)
• Hepatomegaly
• Dark urine (84%)
• Pale stools, usually transient
• Abdominal/RUQ pain
• Fatigue
• Meningismus (occasional)
• Arthralgia/arthritis
• Vast majority are minimally symptomatic or asymptomatic

What Causes Disease?

Hepatitis B virus

Risk Factors

• Health care workers/other occupational risks
• Hemodialysis
• Recipients of blood and/or blood products (esp. prior to 1992)
• IV drug users 60-70% of new infections
• Sexually active homosexual males
• Household exposure
• Intimate exposure
• Positive needlestick
• Transplanted organs
• Snorting cocaine
• Recent body piercing; tattoos less likely, role controversial
• Perinatal transmission of neonate of hepatitis B infected mother rare with HCV unless HIV positive

Diagnosis of Disease

Differential Diagnosis

Infectious mononucleosis, primary or secondary hepatic malignancy, ischemic hepatitis, drug-induced hepatitis, alcoholic hepatitis, autoimmune hepatitis, Wilson disease, rheumatic and skin manifestation may suggest immunologic disorder

Laboratory

• Marked elevation of AST/ALT (acute hepatitis, particularly ALT, 400-several thousand U/L)
• Mild elevation of alkaline phosphatase
• Bilirubin from normal to markedly elevated; with elevation, conjugated and unconjugated fractions usually increased
• For severe hepatitis, measure PT and PTT, albumin, electrolytes, glucose and CBC
• If HBV chronic, test HBV DNA titer
• Patients with severe HBV infection should be tested for coinfection or superinfection with HDV Testing for HDV also indicated in sexually active gay men, and those with history of IV drug abuse.
• HBeAg indicates high infectivity (horizontal and vertical transmission)
• Persistence > 6 months indicates probable chronic liver disease

Drugs that may alter lab results: Corticosteroids, other immunosuppressive drugs

Disorders that may alter lab results: Leucopenia may exacerbate viral replication

Pathological Findings

• Liver biopsy in persistent or chronic disease shows wide range of histologic changes (variable inflammation and/or necrosis, cholestasis, fibrosis, cirrhosis or chronic active hepatitis)
• Clinical course may not predict severity of histopatho-logic changes
• Microvesicular steatosis and lymphoid aggregates suggest hepatitis C infection

Special Tests

Liver biopsy usually needed for determining type and extent of liver injury in persistent disease and to exclude other diseases. Also, usually necessary prior to start of antiviral treatment such as interieron alfa.

Imaging

• Usually helpful
• Ultrasound may demonstrate ascites or exclude obstruction. Helpful when cancer is suspected.
• CTwith IVcontrast and MRI in selected cases
• Early cirrhosis usually not detected by imaging studies — need liver biopsy

Diagnostic Procedures

• History; exposure source; exclude drugs; both prescription, over the counter and herbs
• Tenderness overthe liver; may be hepatomegaly
• Jaundice may not be present in most
• Serum “liver function tests” often elevated before bilirubin increases; measure aminotransferases in acute illnesses when there is no evident cause
• Serum biochemical markers, diagnosis in 90% of patients

Treatment (Medical Therapy)

Appropriate Health Care

• Outpatient care usual; severe cases need inpatient care

General Measures

• Monitor: coagulation defects, fluid and electrolytes, acid-base imbalance, hypoglycemia, impairment of renal function
• Report acute cases to public health department
• Need multidisciplinary approach, especially in those with cirrhosis. Familiarity with risks, side effects and monitoring for liver cancer and mutations of hepatitis B is essential.

Surgical Measures

Consider liver transplantation in fulminant acute hepatitis/end-stage liver disease (HCV) and in early stages of primary liver cancer. Refer to a tertiary care center with liver and other organ transplant facilities.

Activity

As tolerated

Diet

Adequate calories; balanced nutrition

Patient Education

• Avoid sharing razors, tooth brushes and nail clippers
• Wash and cover cuts and bruises
• Proper use and disposal of needles
• Proper hygiene, particularly food handlers
• HBV sexually transmitted
• HBV present in saliva, vaginal secretions, vaccinate sexual partner, household contacts against HAV, HBV

Hepatitis B

Medications (Drugs, Medicines)

Drug(s) of Choice

• Acute hepatitis B: Antiviral therapy not indicated as spontaneous resolution occurs in about 95%; others need close monitoring for chronicity or fulminant hepatic failure.
• Chronic hepatitis B: persistent hepatitis B surface antigenemia > 6 months

– Interieron-alpha (IFN-a) and lamivudine (LAM) are equally effective.

– Goals of therapy: Decrease in HBV DNA to undetectable level; loss of hepatitis Be antigen and appearance of anti -Hbe; loss of HBsAg from serum is seldom achieved but will be ideal.

Contraindications:

Interieron: platelet count < 50,000. Mouse immunoglobulin, egg protein or neomycin allergy. Corticosteroids may add to morbidity/increased mortality.

Precautions:

• Other disorders of coagulation, myelosuppression. seizures, depression (esp. suicide ideation), pregnancy fertile age group, lactation
• Increased serum triglycerides may occur during IFN therapy; may cause abnormal ALT
• Psychiatric evaluation may be prudent prior to IFN treatment
• Lamivudine resistant mutations

Significant possible interactions:

Refer to manufacturer’s profile of each drug

Alternative Drugs

Adefovir 10 mgqid, Famciclovir (Famvir) 500 mg tid for chronic hepatitis B

Patient Monitoring

• Serial measurement of serum AST/ALT
• Appropriate serum viral markers useful for evaluation of recovery or progression
• Liver biopsies in chronic disease; in acute cases if diagnosis remains in doubt
• Monitor for metabolic complications
• WBC, platelets with interieron alfa therapy
• Chronic HBV, HBV-DNA valuable for prediction of favorable response to IFN. High pretreatment ALT and low pretreatment HBV-DNA associated with favorable response.
• Monitor for hepatic decompensation (ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, etc) in cirrhotics

Prevention / Avoidance

• General

– Screen blood products

– Proper disposal of needles

– Good sanitation, hygiene

– Maximum infectivity 2 weeks before jaundice

– May be endemic in institutions; day care centers

– vaccinate for HBV

– HBV transmitted sexually, perinatally, occupationally and via parenteral drug use (e.g., shared needles); also enterically.

• Specific

– Hepatitis B vaccine. A new hepatitis B vaccine to include pres, and S2 antigens will be available soon: more effective especially in nonresponders.

– High risk groups: hepatitis B human immune globulin within 24 hr of exposure (0.06 mL/kg IM)

– HBV screening in pregnant women; vaccinate all infants at birth.

Possible Complications

Acute or subacute necrosis, chronic active or chronic hepatitis, cirrhosis, hepatic failure; hepatocellular carcinoma (HBV, HCV)

Expected Course / Prognosis

• Recovery from acute infection in 95% of patients
• Severity of hepatic encephalopathy best predictor of poor survival in hepatic failure
• HBV (mortality 1 %) and HDV (with icterus, mortality 2-20%) more severe symptoms; often leads to persistent/chronic liver disease, cirrhosis, liver failure, hepatocellular carcinoma; more severe problems if impaired immune function. Follow treatment with HBV-DNA levels.

Miscellaneous

Associated Conditions

• Arthritis, urticaria, immune complex nephritis (particularly membranous glomerulopathy), anemias (including aplastic anemia), dermatitis and cardiomyopathy (usually with HBV, rare with HCV).

Age-Related Factors

Pediatric: HBV more acute, less prolonged, less complications, but may become chronic.

Geriatric: N/A

Others: Alcohol abuse a major factor for chronic liver disease. Measure viral biochemical markers in patients with alcoholic liver disease (especially anti-HCV).

Pregnancy

• Test, in later gestation, for HBsAg
• HBV transmitted vertically (< 10%) as well as perinatally and produces carrier state in 30%. Give infant HBIg 0.5 mL and HBV vaccine (Recombivax HB; separate sites) within 12 hrs of birth followed by HBV vaccine, 0.5 mL M at ages 1 and 6 months. Check HBsAg and HBsAb at age 12 months
• Vertical transmission increased in HIV

International Classification of Diseases

070 Viral hepatitis

See Also

Hepatitis C
Immunizations
Hepatitis A

Abbreviations

HBsAg = hepatitis B surface antigen
HBeAg = hepatitis Be antigen

Hepatitis C

Description of Medical Condition

A systemic viral infection primarily involving the liver

System(s) affected: Gastrointestinal

Genetics: Some predisposition to immunologic manifestations; DR4 — positive increase with concurrent immunologic disease

Incidence/Prevalence in USA:

16% of sporadic hepatitis; 40,000 new cases year; 3 million chronically infected (85% of infected); donor blood screening has reduced risk

Predominant age: All ages

Predominant sex: Male = Female

Medical Symptoms and Signs of Disease

• Fever (60%)
• Malaise (67%)
• Nausea and vomiting
• Anorexia (54%)
• Jaundice (34%)
• Hepatomegaly
• Dark urine (84%)
• Pale stools, usually transient
• Abdominal/RUQ pain
• Fatigue (major complaint)
• Meningismus (occasional)
• Arthralgia/arthritis
• Vast majority are minimally symptomatic or asymptomatic

What Causes Disease?

Hepatitis C virus

Risk Factors

• Health care workers/other occupational risks
• HCV transmitted through blood or its products; in 40%. mode unknown
• Hemodialysis
• Recipients of blood and/or blood products (esp. prior to 1992)
• IV drug users 60-70% of new infections
• Sexually active homosexual males (much more likely with hepatitis B than with C)
• Household exposure
• Intimate exposure
• Positive needlestick
• Transplanted organs
• Snorting cocaine
• Recent body piercing; tattoos less likely, role controversial
• HIV positivity increases risk of hepatitis C or C virus infection in coinfected patients
• Perinatal transmission of neonate of hepatitis B infected mother rare with HCV unless HIV positive

Diagnosis of Disease

Differential Diagnosis

Infectious mononucleosis, primary or secondary hepatic malignancy, ischemic hepatitis, drug-induced hepatitis, alcoholic hepatitis, autoimmune hepatitis, Wilson disease, rheumatic and skin manifestation may suggest immunologic disorder

Laboratory

• Marked elevation of AST/ALT (acute hepatitis, particularly ALT, 400-several thousand U/L); HCV may have normal ALT; AST/ALT ratio =>1 associated with cirrhosis in chronic HCV
• Mild elevation of alkaline phosphatase
• Bilirubin from normal to markedly elevated; with elevation, conjugated and unconjugated fractions usually increased

Positive serum markers in hepatitis C

Status Marker

A, C Anti-HCV ELISA III or RIBA HCV RNA: (qual. S quan.) Genotypes I-IV

Infection status: A=acute C=chronic

• For severe hepatitis, measure PT and PTT, albumin, electrolytes, glucose and CBC
• Persistence > 6 months indicates probable chronic liver disease
• Acute, ongoing HCV, confirm by other markers, RIBA. HCV-RNA (for chronic HCV); >viral counts, genotypes 1, 2, 3 & 4
• In early acute HCV infection, anti-HCV may be negative; may need retest in 3-6 weeks
• HCV-RNA becomes positive early in acute cases
• HCV genotypes may be useful. Genotypes with favorable prognosis — 2a, 2b, 3a; less favorable 1a, 1 b

Drugs that may alter lab results: Corticosteroids, other immunosuppressive drugs

Disorders that may alter lab results: Leucopenia may exacerbate viral replication

Pathological Findings

Liver biopsy in persistent or chronic disease shows wide range of histologic changes (variable inflammation and/or necrosis, cholestasis, lymphoid aggregate, steatosis, fibrosis, cirrhosis or chronic active hepatitis. Clinical course may not predict severity of histopathologic changes. Microvesicular steatosis and lymphoid aggregates suggest hepatitis C infection.

Special Tests

Liver biopsy usually needed for determining type and extent of liver injury in persistent disease and to exclude other diseases. Also, usually necessary prior to start of antiviral treatment such as interieron-alfa.

Imaging

Usually helpful. Ultrasound may demonstrate ascites or exclude obstruction. Helpful when cancer is suspected. CTwith IV contrast and MRI in selected cases. Early cirrhosis usually not detected by imaging studies — need liver biopsy.

Diagnostic Procedures

• History; exposure source; exclude drugs; both prescription, over the counter and herbs
• Tenderness overthe liver; may be hepatomegaly
• Jaundice may not be present in most
• Serum “liver function tests” often elevated before bilirubin increases; measure aminotransferases in acute illnesses when there is no evident cause
• Serum biochemical markers for each virus, diagnosis in 90% of patients

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient care usual; severe cases need inpatient care

General Measures

• Monitor: coagulation defects, fluid and electrolytes, acid-base imbalance, hypoglycemia, impairment of renal function
• Report acute cases to public health department
• Need multidisciplinary approach monitored by experienced physician-led-team
• Careful patient selection essential

Surgical Measures

Consider liver transplantation in fulminant acute hepatitis/end-stage liver disease and in early stages of primary liver cancer. Refer to a tertiary care center with liver and other organ transplant facilities.

Activity

As tolerated

Diet

Adequate calories; balanced nutrition

Patient Education

• Avoid sharing razors, tooth brushes and nail clippers
• Wash and cover cuts and bruises
• Proper use and disposal of needles
• Proper hygiene, particularly food handlers
• Sexual transmission low, but does occur

Medications (Drugs, Medicines)

Drug(s) of Choice

• Acute hepatitis C: Antiviral therapy is highly effective for acute infections. Interieron-alfa 5 mg SC or IM dailyfor HCV-RNA for 4 weeks followed by 3 times per week for 20 weeks.
• Chronic hepatitis C: pegylated interieron + ribavirin

– Pegylated interferon-alpha 2b 1.5 mcg/kg/week

– Pegylated interferon-alpha 2a 180 meg/week

– Ribavirin 800-1200 mg po bid in combination with pegylated interferon

Contraindications:

Interferon: platelet count < 50,000. Mouse immunoglobulin, egg protein or neomycin allergy. Corticosteroids may add to morbidity/increased mortality.

Precautions:

• Other disorders of coagulation, myelosuppression, seizures, depression (esp suicide ideation), pregnancy, fertile age group, lactation
• Ribavirin may induce hemolytic anemia (hemoglobin 2 gm/dL below pretreatment) is common. Avoid in pregnancy.
• Increased serum triglycerides may occur during IFN therapy; may cause abnormal ALT. Measure HCV-RNA to assess response in such patients.
• Psychiatric evaluation may be prudent prior to IFN treatment

Significant possible interactions:

Refer to manufacturer’s profile of each drug

Alternative Drugs

N/A

Patient Monitoring

• Serial measurement of serum AST/ALT
• Appropriate serum viral markers useful for evaluation of recovery or progression
• Liver biopsies in chronic disease; in acute cases if diagnosis remains in doubt
• Monitor for metabolic complications
• WBC, platelets with interieron-alfa therapy
• Lower viral load, genotypes 2 and 3 and absence of cirrhosis are predictors of favorable therapeutic response. Undetectable HCV-RNA (quantitative serum HCV-RNA) at 12 weeks is associated with sustained response. Persistently positive HCV-RNA at 24 weeks indicates lack of response; prolonged course is unlikely to be beneficial.
• Monitor for hepatic decompensation (ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, etc) in cirrhotics
• Goal of therapy is eradication of hepatitis C virus; HCV-RNA test should become persistently undetectable
• Early virologic response is defined as >2 log decrease in HCV-RNA level after 12 weeks of treatment
• In patients with cirrhosis the risk of hepatic cellular carcinoma is high (20% life-time risk). Monitor for hypervascular lesions by imaging (ultrasound, helical CT) every 6 months.

Prevention / Avoidance

• No specifics on prevention/avoidance
• Maximum infectivity 2 weeks before jaundice

Possible Complications

• Acute or subacute necrosis, chronic hepatitis, hepatic failure
• Primary liver cancer risk
• HCV-associated cirrhosis: 1-3% per year, lifetime risk 20%. Cirrhosis patients need surveillance for hepatocel-lular carcinoma.

Expected Course / Prognosis

• Severity of hepatic encephalopathy best predictor of poor survival in hepatic failure
• in HCV, regardless of severity:

– > 80% progress to chronic hepatitis

– 20-50% to cirrhosis, and some, liver failure

– Typically slow progression 10-30 years

– May progress to HCC, but IFN may decrease HCC risk

– Associated with type II Al

– Chronic HCV unlikely to clear HCV-RNA spontaneously

– HCV after needlestick, usually sustained IFN response

– Final phase HCV rare cause of fulminant hepatic failure

• Alcohol increases severity of chronic HCV

Miscellaneous

Associated Conditions

• Arthritis, urticaria, immune complex nephritis (particularly membranous glomerulopathy), anemias (including aplastic anemia), dermatitis and cardiomyopathy (rare with HCV). HCV implicated in sporadic form of idiopathic mixed cryoglobulinemia, porphyria cutaneous tarda, polyarteritis nodosa.
• HIV-HCV: more severe course

Age-Related Factors

Pediatric: Uncommon

Geriatric: N/A

Others: Alcohol abuse a major factor for chronic liver disease from HCV. Measure viral biochemical markers in patients with alcoholic liver disease (especially anti-HCV).

Pregnancy

Vertical transmission increased in HIV

International Classification of Diseases

070 Viral hepatitis

See Also

Hepatitis A
Hepatitis B
Immunizations

Abbreviations

PCR = polymerase chain reaction
IFN = interferon

HCC = hepatocellular carcinoma
Al = autoimmune hepatitis