Hepatitis

1. In a patient presenting with hepatitis symptoms and/or abnormal liver function tests, take a focused history to assist in establishing the etiology (e.g., new drugs, alcohol, blood or body fluid exposure, viral hepatitis).
2. In a patient with abnormal liver enzyme tests interpret the results to distinguish between obstructive and hepatocellular causes for hepatitis as the subsequent investigation differs.
3. In a patient where an obstructive pattern has been identified,
   1. Promptly arrange for imaging,
   2. Refer for more definitive management in a timely manner.
4. In patients positive for Hepatitis B and/or C,
   1. Assess their infectiousness,
   2. Determine human immunodeficiency virus status.
5. In patients who are Hepatitis C antibody positive determine those patients who are chronically infected with Hepatitis C, because they are at greater risk for cirrhosis and hepatocellular cancer.
6. In patients who are chronically infected with Hepatitis C, refer for further assessment and possible treatment.
7. In patients who are at risk for Hepatitis B and/or Hepatitis C exposure,
   1. Counsel about harm reduction strategies, risk of other blood borne diseases,
   2. Vaccinate accordingly.
8. Offer post-exposure prophylaxis to patients who are exposed or possibly exposed to Hepatitis A or B.
9. Periodically look for complications (e.g., cirrhosis, hepatocellular cancer) in patients with chronic viral hepatitis, especially hepatitis C infection.

See abnormal liver enzyme tests

General Overview

• Hepatitis: Acute vs. Chronic (> 6 months)
• Cirrhosis: Compensated vs Decompensated (decreased function)
  • Platelet count helpful for early signs of liver disease and varices
    • AST/platelet ratio index <0.5 unlikely fibrosis

DDx

• Noninfective
  • Alcohol
  • NAFLD/NASH
  • Drug-induced (Acetaminophen, INH, tetracyclines, antiepileptics/phenytoin)
  • Autoimmune
• Infective
  • Hepatitis B/C/D (Blood/body fluid/sexual)
  • Hepatitis A/E (Fecal/oral, usually self-limited)

History

• Exposures
  • Medication history (OTC, herbal and dietary supplements)
  • Alcohol consumption
  • IVDU / Needle stick exposures
  • Tattoos or body piercings
  • High-risk sexual contact
  • Blood transfusion prior to 1992
  • Travel to areas endemic for hepatitis
• Signs and Symptoms
  • Light-colored stools, pruritus, dark urine (bilirubinuria)
  • Acute pain in RUQ, ascites (hematologic diseases, may have hepatic vein thrombosis)
  • Fever/weight loss/night sweats (acute viral hepatitis of any etiology)
• Prior hepatobiliary disease (including gallstones)
• Prior inflammatory bowel disease (autoimmune)
• History of diabetes, skin pigmentation, cardiac disease, arthritis, hypogonadism (hemochromatosis)
• History of blood disorders (hemolysis)
• Family history of inherited liver disorders

Physical Exam

• Jaundice
• Malnutrition
  • Temporal and proximal muscle wasting
• Hormonal
  • Spider nevi, caput medusa, palmar erythema, gynecomastia, testicular atrophy
• Hepatomegaly, splenomegaly
• Decompensated Cirrhosis
  • Ascites, peripheral edema
  • Neuro
    • Hepatic encephalopathy
    • Asterixis
• Alcohol abuse
  • Dupuytren’s contracture, parotid enlargement, testicular atrophy

Serology

• Anti-HAV Ab: Past or current infection
• Anti-HCV Ab: Past or current infection
• HBsAg: Infection (if persists >6 months = chronic infection)
• Anti-HBs: Immunity due to infection or immunization
• Anti-HBc total (IgM and IgG): Past or current infection (IgG usually persists for life)
• HBeAg: High infectivity (viral replication)
• Anti-HBe:
  • Appears with recovery from acute infection
  • In chronic infection, the presence of Anti-HBe suggests low infectivity

Isolated Anti-HBc positive

• DDx
  • False positive result/lab error (most common)
    • Positive Anti-HBe infers prior HBV exposure, and unlikely false positive
  • "Window phase" - resolving acute infection before the appearance of anti-HBs
  • "Remote resolved HBV infection" - undetectable anti-HBs due to a decline in antibody titre over time
  • "Occult HBV", chronic infection with undetectable HBsAg (rare)
• Consider
  • HBV DNA viral load
    • If negative
      • Booster (or complete series) and follow-up HBsAb after 1-2 months if responds with immunity
      • If no response to booster to ensure not occult HBV, consider repeat viral load q3-6 months until undetectable x 2-3
  • Test co-infection HIV/HCV
  • See below (Positive Hepatitis) if chronic carrier

Screening

• Hepatitis B screening (HBsAg, anti-HBs, anti-HBc total)
  • Review HBV immunization history, previous testing
  • Consider screen if high-risk (eg. exposures, travel, family history, abnormal liver tests)
  • Screen all pregnancy, HIV/HCV, immunocompromised (or planned therapy)
• Hepatitis C screening
  • IVDU, needle-stick injury, hemodialysis, pregnancy
  • Canadian Taskforce does not recommend people born in Canada between 1950-1975 be screened

Prevention

• Abstain from alcohol
• Vaccination against Hep A/B
• Screen pregnancy
  • Mothers with high HBV viral loads should be given antiviral therapy to further reduce the risk of infection in the newborn
    • Follow-up infants (HBV vaccine and HBIG within 12h after birth, with repeat vaccine at 1 and 6 months)

Hepatitis Post-Exposure Prophylaxis (PEP)

• Clean wounds, avoid any further blood/body fluid exchange until cleared
• Vaccinate Hep A/B as indicated
• Screen all contacts and offer PEP as indicated

Hepatitis A PEP

• Hygiene practices: Handwash, avoid tap water, raw foods, heating foods >85°C
• Hep A PEP only indicated in close personal contacts, child care contacts, food handlers (not warranted in a single case of Hep A in school or hospital)
  • For healthy individuals aged 12 months to 40 years
    • HAV Vaccine (Havrix 1mL IM x1)
  • For individuals ≥41 years or <12 months, immunocompromised, chronic liver disease, allergic to the vaccine
    • Hepatitis A immune globulin 0.02 mL/kg IM x1
  • The combination vaccine TWINRIX should not be used for postexposure prophylaxis

Hepatitis B PEP

• PEP not required if either source or exposed has either
  • Recorded previous (at any time) anti-HBs ≥10 IU/L
  • History of recovery from HBV infection
• Hep B vaccine (0, 1-2, and 4-6 months) if source HBsAg-positive or HBV-unknown
  • Within 24 hours of exposure, and complete three-dose series (zero, one, six months) if not vaccinated
• HBIG 0.06 mL/kg IM x1 if source HBsAg-positive or high risk (e.g., IVDU, MSM)
  • As soon as possible, within 7 days of percutaneous exposure or within 14 days of sexual exposure
  • Repeat dose at 28-30 days after exposure in non-responders to Hepatitis B vaccine or in patients who refuse vaccination
• If PEP given, do anti-HBc and HBsAg after 6 months to assess for HBV transmission

Hepatitis C

• No PEP recommended
• Close observation for those who had percutaneous or high-risk sexual exposure (unless source negative HCV RNA)
  • If source HCV RNA positive, repeat HCV RNA at 4w, and HCV RNA + HCV Ab at 3 and 6 months
  • If source HCV RNA unknown, repeat HCV Ab six months after exposure
• Delay treatment for six months minimum to monitor for spontaneous clearance of HCV RNA

Positive Hepatitis B or C

• Education on harm reduction
  • Inform health care providers (dentist, nurse, other physicians) and other providers eg. (acupuncturist, tattoo artist) of infection
  • Do not donate blood/semen/tissues
    • Safely dispose of blood (hygiene products, floss, bandages, needles)
    • Cover cuts/sores
    • Do not share personal hygiene materials and sharp instruments (razors, nail clippers, toothbrushes, glucometers)
  • Ensure all partner/household members/drug use partners are tested and immunized if susceptible (Hep B vaccine free for susceptible contacts)
    • Condom-use until partners test immune
  • Avoid medication or alternative therapies (herbals) that may affect or be affected by liver
  • Go to ER if black stools or vomiting blood
• Labs
  • Bilirubin (total and direct), albumin, INR (PT), creatinine
  • ALT, AST, ALP
  • CBC
  • Test co-infection HIV status, Hep B/C
  • Assess infectiousness - HBV DNA, HbeAg
• Vaccinate Hep A/B as indicated
• Screen all contacts and offer PEP/vaccinations as indicated
• Follow-up
  • Psychiatric illness, alcohol/substance use
  • Complications
    • Hepatocellular carcinoma
    • Decompensated cirrhosis
    • Ascites
    • Upper GI Bleed
    • Encephalopathy

HBsAg positive

• Management focus on relief of symptoms, monitoring, prevention of complications and transmission
  • Does not require antiviral treatment for acute Hep B as most (95%) will clear
  • Refer if deteriorating liver failure (INR, bilirubin, platelet, encephalopathy)
• Repeat HBsAg at 6 months after baseline to confirm Chronic carrier (95% clear)
  • If confirmed chronic carrier
    • HIV/HCV (if not done already)
    • HBeAg
    • Repeat labs
      • ALT q6 months
      • HBV DNA (viral load) q1 year
    • Ultrasound (+/- AFP) q6-12 months for HCC
      • Cirrhosis
      • HIV/HCV co-infection
      • African descent>20yo
      • Men>40yo, Women>50yo
      • Family history of hepatoma
    • Referral to specialist (treatment with interferon injections or oral nucleoside/nucleotide analogues)
      • Usually if elevated ALT or HBV DNA >2000 IU/mL

Anti-HCV Ab positive

• HCV RNA testing for Chronic carrier (20% clear)
  • If positive, add HCV genotype
• Refer to hepatologist for treatment (eg. Harvoni x 12w) or liver transplant
  • Level of fibrosis predicts outcome (Metavir scoring system)
• Screening in cirrhosis,
  • Upper endoscopy q1-2y for varices
  • Liver ultrasound q6-12mo for HCC