Hepatitis A, B, C, D, E: Causes and Facts

• Hepatitis refers to acute or chronic liver inflammation.
• Hepatitis can be caused by viruses, alcohol, medications, autoimmune diseases, or metabolic defects.
• Chronic liver disease (CLD) is indicated by inflammation lasting more than 6 months.
• Cirrhosis can result from CLD.
• Liver failure and the need for a transplant is possible.

Hepatitis A, B, C, D, and E

• Hepatitis A and E are contracted from contaminated food or water.
• Parenteral contact with infected bodily fluids causes Hepatitis B, C, and D.
• HBV spreads through infected blood, semen, and other bodily fluids.
• HCV is primarily transmitted via infected blood.
• Excessive alcohol intake can cause fat and inflammation in the liver, leading to cirrhosis.
• Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are associated with metabolic syndrome.

Hepatitis Facts

• Hepatitis A and E are self-limiting.
• Half of new Hepatitis B (HBV) infections are asymptomatic.
• Hepatitis C virus (HCV) is the most common chronic blood-borne pathogen in the US.
• Cirrhosis will develop in about 5–25% of people with chronic HCV over 10–20 years.
• NAFLD is the most rapidly increasing type of chronic liver disease (CLD).

Population, Prevalence, and Incidence

• Approximately 2.3 billion people worldwide are infected with one or more hepatitis viruses.
• 2.4 million people in the United States are estimated to be living with HCV.
• 4.1 million US adults have a past or current HCV infection.
• In 2017, there were 3,216 cases of acute HCV infection reported, with a higher incidence among young IV drug users.
• Autoimmune hepatitis is a rare condition with an incidence of 1.9 in 100,000, most commonly found in women.

Risk Factors

• Intravenous drug use is a risk factor
• Invasive medical procedures
• Injuries from needlesticks
• Risky behavior
• HIV infection
• Sharing of personal items
• Unregulated tattoos and body piercings
• Birth to a mother with hepatitis C
• Blood products received before universal blood product testing in 1992
• Excessive alcohol intake
• Metabolic syndrome
• The most common medications that cause drug-induced liver injury, include acetaminophen and amoxicillin-clavulanic acid

Clinical Presentation of Acute Hepatitis

• Jaundice and dark urine are symptoms
• Extreme fatigue
• Nausea and vomiting
• Abdominal pain
• Weight loss

Physical Exam Findings

• Tender or enlarged liver, normally 6-12cm.
• Liver span is 10.5cm for males and 7 cm for females, liver palpated more than 1-2cm below the right coastal margin is enlarged.
• Mild to moderate dull pain in the right upper quadrant (RUQ) or epigastrium.
• Anorexia, nausea, malaise, and low-grade fever.
• Needle tracks on hands, arms, and antecubital fossae.

Acute Hepatitis Diagnostics

• CBC may show leukocytosis or anemia, especially in alcoholics.
• CMP may show elevated ALT and AST, elevated bilirubin and alkaline phosphatase, low albumin, and abnormal glucose and electrolyte levels.
• Elevated ESR and CRP levels.
• Abnormal PT, PTT, and INR results.
• Elevated ammonia levels indicate neurologic symptoms, pointing to hepatic failure.

Diagnostic Testing

• Ultrasonography is the most cost-effective method.
• Computed tomography can show the presence of tumors, fatty tissue, and liver size.
• Magnetic resonance cholangiopancreatography (MRCP).
• Liver biopsy if diagnosis is inconclusive by ultrasound or CT guidance.

Laboratory Testing for Hepatitis

• Serologic tests for acute infections include IgM anti-HAV for Hepatitis A and HBsAg plus IgM anti-HBc for Hepatitis B.
• Hepatitis C has no serologic marker for acute infection.
• Serologic tests for chronic infections: Hepatitis A is not applicable due to no chronic infection.
• Hepatitis B chronic infection tests should include three HBV seromarkers: HBsAg, anti-HBs, and Total anti-HBc.
• The Hepatitis C assay tests for anti-HCV, qualitative and quantitative nucleic acid tests (NAT) to detect and quantify the virus presence (HCV RNA).

Hepatitis B Serologic Markers

• HBeAg marker indicates active replication of the HBV virus and increased risk of infectiousness and liver damage, but may be absent despite active replication in serration mutations
• HBsAg indicates infection with acute or chronic hepatitis (>6 months).
• Anti-HBs indicates recovery and immunity from HBV infection and can indicate immunity from immunization.
• Anti-HBc indicates previous or ongoing infection with hepatitis B and persists for life.
• IgM anti-HBc (IgM) indicates acute infection if present for less than 6 months, and usually indicates chronic infection if present for more than 6 months
• Anti-HBe indicates recovery and immunity from HBV infections and should be present with anti-HBc and anti-HBs.
• HBV DNA detects the quantity of HBV viral genetic material in the blood, a positive test indicates HBV is active, used to determine the effect of antiviral therapy in treatment of chronic HBV (CBV).

Differential Diagnoses

• Hemolytic-Uremic Syndrome
• Reye's Syndrome
• Chronic Hemolytic Disease
• Wilson's Disease
• Cystic Fibrosis
• Other Viral Infections (EBV, CMV, Coxsackievirus Herpes)
• Acute Cholangitis (Infection of the Bile Duct)
• Drug Toxicity and Poisoning
• Hepatic Malignancy
• Autoimmune, Alcoholic, or Ischemic Hepatitis
• Acute Cholecystitis
• Disseminated Sepsis

HCV Screening

• The USPSTF has recently expanded screening recommendations to include all adults aged 18 to 79 years.
• There needs to be a focus on low-income, uninsured, and underserved populations where screening rates have remained low.
• Stigmatization, anxiety, and patient labeling discourage people from getting screened for HCV.

Prevention and Pharmacological Interventions

• Hepatitis A: Routine vaccination is recommended for children aged 12–23 months, with catch-up vaccinations for children and adolescents aged 2–18 years, and for adults at risk. There is no medication available, best addressed through supportive treatment
• Hepatitis B: Routine vaccination (2, 3, or 4 doses) is recommended for infants, children, and adolescents younger than 19 years of age, and unvaccinated adults who are in high-risk categories. Acute: no medication available, and best addressed through supportive treatment. For Chronic infections: Pegylated interferon alfa-2a (Pegasys) 180 mcg subq weekly for 48 weeks, Entecavir (Baraclude) 0.5 to 1 mg PO daily, and Tenofovir (Viread) 300 mg PO daily or Tenofovir alafenamide (Vemlidy) 25 mg PO daily
• Hepatitis C: There is no vaccine. Oral antiviral therapy is treatment-Naive for Adults Without Cirrhosis (Any Genotype). Therapy includes Glecaprevir (300 mg)/pibrentasvir (120 mg) PO for 8 weeks, and Sofosbuvir (400 mg)/velpatasvir (100 mg) PO for 12 weeks.
• Oral antiviral therapy Treatment-Naive Adults With Compensated Cirrhosis: Treatment includes Genotype 1-6: Glecaprevir (300 mg)/pibrentasvir (120 mg) PO for 8 weeks
• Genotype 1, 2, 4, 5, or 6 : Sofosbuvir (400 mg)/velpatasvir (100 mg) PO for 12 weeks
• Hepatitis D: No vaccine is available, and there is no specific treatment for acute hepatitis D.
• Hepatitis E: No FDA-approved vaccine is available in the US, and management of acute HEV infection is supportive.

Pharmacological Symptom Management

• Cholestyramine (Questran) is used for pruritus associated with jaundice, 1 packet/scoop 5 mg mixed with food or fluids BID.
• Acetaminophen overdose is treated with N-Acetylcysteine oral regimen (Mucomyst) or IV formulation (Acetadone).
• Rifaximin 550 mg PO every 12 hours, along with a large dose of lactulose, is used for managing hepatic encephalopathy.
• There is no pharmacological treatment for NAFLD; prevention and control of metabolic disorders is imperative.

Evidenced-Based Treatment Approach: Non-Pharmacological

• Education about the disease
• Vaccinations for other viral hepatitis infections
• Abstinence from alcohol
• Avoidance of large doses of hepatotoxic drugs like acetaminophen or iron.
• Refraining from starting new medications.
• For acute hepatitis, a high-calorie diet (best tolerated in the morning) and maintaining fluid balance is important.
• Monitoring clotting factors, liver function, and metabolic disease.
• For chronic hepatitis, performing serology, radiology, or pathology testing, screening or monitoring for HHC with liver ultrasound/biopsy, and vaccination against pneumococcal infections.

Geriatric Considerations

• Liver size decreases by 25% between the ages of 20 and 70 years.
• Drug metabolism by the liver is impaired.
• Prolonged liver metabolism causes increased side effects.
• Polypharmacy increases the risk for drug-drug interactions with antiviral drugs.

Follow Up

• HAV: Measure Liver Function Tests (LFTs) 6 to 12 months after acute illness.
• HBV: Measure HBsAg or HBeAg, and LFTs every 2 weeks until normalization starting 6 months after acute illness.
• Chronic HBV: Perform hepatocellular cancer (HCC) surveillance with imaging and LFTs every 3 to 6 months.
• High-risk for HCV: Liver ultrasound every 6 months, HCV RNA annually, plus measure ALT, AST, or bilirubin levels.
• Post antiviral therapy for Hepatitis C: Confirm virologic cure and LFTs 12 weeks or later after therapy.
• Patients with noncirrhotic Hepatitis C who achieve SVR: no liver-related follow-up is recommended.
• NAFLD: Regular monitoring of LFTs every 6 months.