Signs & Symptoms Of Acute Hepatitis

Signs & Symptoms

Preicteric Phase

  • Nonspecific systemic symptoms (eg myalgia, nausea, vomiting, fatigue, malaise w/ discomfort in the right upper quadrant of the abdomen)
  • Altered sense of smell or taste, coryza, photophobia, headache, cough, diarrhea, dark urine & serum sickness-like syndrome
  • Hepatomegaly, splenomegaly & lymphadenopathy may be seen on physical exam
Icteric Phase
  • Jaundice, usually noted after onset of fever or upon lysis of fever
Fulminant Hepatitis
  • Development of symptoms of hepatic encephalopathy (eg confusion, drowsiness w/in 8 wk of symptoms or w/in 2 wk of onset of jaundice)
  • Hypoglycemia, prolonged prothrombin time (PT)
Important points in the clinical history of patients w/ suspected viral hepatitis
  • Contacts w/ jaundiced patients
  • IV drug use
  • History of blood transfusion
  • Surgery or hospitalizations
  • Family history of chronic liver disease
  • Occupation
  • Food & water sources
Routes of Transmission of Hepatitis
  • Hepatitis A: Oral-fecal
  • Hepatitis B: Perinatal, percutaneous, sexual, close person-to-person contact ie by open cuts & sores
  • Hepatitis C: Blood transfusions, organ transplants, percutaneous (esp IV drug use), sexual, perinatal
  • Hepatitis D: Sexual, percutaneous esp IV drug use
  • Found only in patients w/ hepatitis B since it requires the hepatitis B outer coat
  • Hepatitis E: Oral-fecal, blood transfusion in endemic areas
Incubation Period
  • Hepatitis A: 15-50 days
  • Hepatitis B: 40-180 days
  • Hepatitis C: 20-120 days
  • Hepatitis D: 30-180 days
  • Hepatitis E: 21-60 days
Other Characteristics of Hepatitis Viruses
  • Hepatitis B virus contains a DNA nucleic acid while A, C, & E viruses have an RNA nucleic acid
    • Hepatitis D has an incomplete RNA & needs the B virus to replicate
  • Hepatitis A & E viruses cause epidemics
  • Hepatitis B, C, & D viruses may predispose to chronic disease & hepatic malignancy


Lab Tests
Serological Tests for Viral Hepatitis
Hepatitis A
  • Anti-hepatitis A virus IgM has high sensitivity & specificity & is a marker of acute infection
    • This test remains positive for ≥6 mth
Hepatitis B
  • Usually characterized by the presence of hepatitis B surface antigen (HBsAg) which suggests infectivity
    • Anti-HBs is produced following a resolved infection & is the only HBV antibody marker present after immunization
  • Anti-HBc (anti-core antibody) is the 1st antibody to appear in the serum & is a marker of natural immunity
    • Presence of anti-HBc IgM is diagnostic for acute hepatitis B virus (HBV) infection but may occur during a flare of chronic hepatitis B
    • Its presence indicates an immune response against HBV w/in liver cells & is a specific marker of acute hepatitis B infection
  • Hepatitis B e antigen (HBeAg) is a marker of active viral replication
    • This may be negative at the time that the patient is evaluated for acute hepatitis B since viral replication may have already ceased
  • Patients w/ chronic hepatitis B should also be tested for co-infection w/ hepatitis C virus (HCV), hepatitis D virus (HDV) & human immunodeficiency virus (HIV), if they are at risk for these infections
  • Depending on local health services, the following groups should be tested for chronic HBV infection:
    • Persons born in hyperendemic areas, men who have sex w/ men (MSM), IV drug users, dialysis patients, HIV-positive individuals, pregnant women & family members, household members & sexual contacts of HBV-infected persons
      • Individuals who are seronegative should be vaccinated against HBV
      • HBsAg-positive patients should be evaluated to assess progression of liver disease & need for antiviral therapy
      • Anti-HBs-positive patients have developed natural immunity & do not need to be vaccinated
Hepatitis C
  • Anti-HCV antibodies are the first-line diagnostic test
  • Acute hepatitis C cannot be reliably diagnosed by antibody tests since these often do not become positive until 3 mth after infection
    • If the clinical suspicion is high, the patient should be tested for HCV RNA to establish the diagnosis
    • HCV RNA is used to determine acute or chronic infection
  • Chronic hepatitis C should be confirmed w/ anti-HCV antibodies & HCV RNA
  • Recombinant immunoblot assay (RIBA) may be used to establish the cause of a positive anti-HCV test in a person w/ undetectable HCV RNA
    • A negative RIBA indicates that a positive anti-HCV immunoassay result showed a false-positive result & no further testing is necessary
    • A positive RIBA & ≥2 subsequent tests in which HCV RNA cannot be detected suggest that HCV infection has resolved & no further testing is indicated
    • A positive anti-HCV & negative HCV RNA indicate no active HCV infection but should have HCV RNA retesting after 3 mth to document recovery
  • HCV RNA quantitative testing to determine baseline viral load is recommended before starting antiviral therapy
    • End of therapy is indicated by undetectable HCV RNA in a sensitive assay (<15 IU/mL) 12 & 24 wk after therapy
  • HCV genotype, including subtyping of genotype 1a/1b, should be determined, if possible, in all HCV-infected persons prior to treatment to determine type & duration of therapy & chances of response
    • Genotypes 2 & 3 are easier to treat, require shorter duration of therapy & a lower Ribavirin dose
    • Genotypes 1, 2 & 3 are mainly distributed in the Asia-Pacific region, whereas genotypes 4 & 6 are mainly restricted to the Middle-East & Southeast regions, respectively
  • Liver biopsy may be done if it is thought that the results will influence clinical decision, but biopsy is not mandatory to start therapy in patients w/ genotypes 2 & 3
    • Liver biopsy may be obtained to provide prognostic information
  • Depending on local health services, the following groups should be tested for chronic HCV infection:
    • Persons who have in the recent or remote past used illicit IV drugs
    • Persons w/ conditions associated w/ high prevalence of HCV infection
      • Positive HIV, hemophiliacs who received clotting factor prior to 1987, history of hemodialysis, persons who received blood/blood products or organ transplants prior to 1995, children born to HCV-infected mothers, healthcare workers after needle stick injury or mucosal exposure to HCV-positive blood, current sexual partners of HCV-infected persons
Hepatitis D
  • Confirmed by positive anti-HDV antibody or HDV RNA test
  • Hepatitis D occurs as a co-infection w/ Hepatitis B
Hepatitis E
  • IgM anti-HEV, IgG anti-HEV & hepatitis E virus (HEV) RNA indicate acute hepatitis E infection
    • HEV RNA is detected from serum & stool of infected patients by PCR
Other lab tests that are recommended in patients suspected to have viral hepatitis:
  • Liver function tests (LFTs)
    • Aspartate aminotransferase (AST) & alanine aminotransferase (ALT)
    • Serum bilirubin, alkaline phosphatase (ALP)
  • PT, international normalized ratio (INR)
  • Noninvasive tests such as the aminotransferase/platelet ratio index (APRI) or FIB4 may be used to assess the degree of hepatic fibrosis when resources are limited prior to initiating HCV therapy
    • Transient elastography may be an option for patients w/ contraindications to liver biopsy



Features of Hepatic Decompensation
  • Mental dullness, bilateral asterixis, clinical deterioration
  • PT is 2 sec longer than control or INR >1.5
  • History & physical exam
  • Measure HBeAg, anti-HBe, HBV DNA & ALT & perform liver ultrasound
  • Complete blood count (CBC), PT, serum albumin to determine severity
  • Screen for hepatocellular carcinoma (HCC) in high-risk patients every 6-12 mth using ultrasound & alpha-fetoprotein
If patient meets criteria for chronic hepatitis B:
  • Liver biopsy to grade stage of liver disease as chronic hepatitis B may evolve to cirrhosis & hepatocellular cancer