Diagnosis

Viral hepatitis

Etiology

Cause [gvy][4sg]

• Hepatitis A virus:

  • Fecal-oral contamination from objects, food, or drinks (poor sanitation)

  • Incubation period: 4 weeks

  • Acute hepatitis: malaise, anorexia, nausea, vomiting, and jaundice

  • Usually self-limiting without treatment or severe liver failure with mortality (1%)

  • Hepatitis A infections do not become long-term (chronic)

• Hepatitis B virus:

  • Blood-borne pathogen spreading through blood (IV drugs, MSM) or body fluids (semen, vaginal mucus, saliva, tears and smaller amount in stool, urine, or sweat)

  • Incubation period: 12 weeks

  • Clinical presentation: usually mild self-limiting, rarely fulminant hepatic failure (1%)

  • The risk for chronic infection becomes lower with age:

    • 90% among infants infected at birth

    • 25-50% of children infected at age 1-5

    • 5% of persons infected as adults will become chronically infected

  • Complications: cirrhosis, liver cancer, liver failure, and death

• Hepatitis C virus:

  • Blood-borne pathogen spreading through blood, birth (rare) or body fluids (rare)

  • Incubation period: 8 weeks

  • Approximately 55-85% develop chronic infections with or without symptoms

  • Complications: cirrhosis, liver cancer, liver failure, and death

• Hepatitis D virus:

  • Incubation period: 13 weeks

  • Requires hepatitis B virus for replication (uses HBsAg as envelope protein)

  • May result in a sudden worsening of hepatitis B and fulminant hepatic failure

• Hepatitis E virus:

  • Fecal-oral transmission (contaminated water or maternal-neonatal transmission)

  • Incubation period: 2-10 weeks

  • Chronic infection described in organ transplant recipients

  • Pregnant women infected during the third trimester have a greater than 25% risk of mortality with a risk of fulminant hepatic failure

• Hepatitis G virus (Human Pegivirus)

  • Transmission by blood, sexual contact and vertical transmission

  • Incubation period: 2-3 weeks

  • Presents as a coinfection in patients with chronic hepatitis B or C infections

• Other virus infections that rarely cause hepatitis in the immunocompetent state:

  • Cytomegalovirus (CMV)

  • Epstein-Barr virus (EBV)

  • Herpes simplex virus (HSV)

  • Varicella-zoster virus (VZV)

• Other causes of hepatitis:

  • Infectious: bacteria, protozoa, parasite, fungus

  • Autoimmune

  • Drugs: paracetamol, antibiotics

  • Ischemic

  • Metabolic: Hemochromatosis, Wilson disease, Alpha 1-antitrypsin deficiency

  • Toxin: alcohol, mushroom

  • Pregnancy: HELLP, Preeclampsia

Pathophysiology [4sg]

1. Incubation/Viral Replication Phase:

   • Asymptomatic

   • Positive for markers of hepatitis

2. Prodromal Phase: 

   • Symptoms: anorexia, nausea, vomiting, malaise, pruritus, arthralgia, and fatigue

   • Mimicking gastroenteritis or any systemic viral infection 

3. Icteric Phase:

   • Dark-colored urine

   • Pale-colored stool

   • Jaundice

   • Right upper quadrant pain

   • Hepatomegaly

   • Elevated liver enzymes

4. End-phase:

   • Convalescent Phase:

     • Resolution of symptoms

     • Liver enzymes returning to normal levels

   • Acute fulminant hepatic failure:

   • Chronic hepatitis

Complications [4sg]

• Acute fulminant liver failure

• Hepatic encephalopathy

• Portal hypertension

• Ascites

• Spontaneous bacterial peritonitis

• Variceal bleeding

• Hepatorenal syndrome

• Chronic infection --> Chronic liver failure

  • Cirrhosis

  • Hepatocellular carcinoma

Epidemiology

Incidence per 100.000 [gvy][ake][wp4][ngf][6yk]

Approach

• Blood test: ASAT, ALAT, PT-INR, Bilirubin, Albumin, GGT, ALP

• Ultrasound

• CT abdomen

• ERCP/MRCP

• Liver biopsy

• Serelogy/PCR-algorythm:

  • Hepatitis A virus:

    • anti-HAV IgM pos --> acute infection

    • anti-HAV IgG pos --> immune (natural infection)

    • HAV-PCR --> detection of Hepatitis A Virus in stool, blood, liver tissue

  • Hepatitis B virus:

    • HbsAg neg / anti-HBc neg / anti-HBs neg --> susceptible

    • HbsAg neg / anti-HBc pos / anti-HBs pos--> immune (natural infection)

    • HbsAg neg / anti-HBc neg / anti-HBs pos --> immune (vaccination)

    • HbsAg pos / anti-HBc pos / anti-HBc IgM pos / anti-HBs neg --> acute infection

    • HbsAg pos / anti-HBc pos / anti-HBc IgM neg / anti-HBs neg --> chronic infection

    • HbsAg neg / anti-HBc pos / anti-HBs neg --> unclear interpretation: resolved infection, false positive, low level chronic infection

  • Hepatitis C virus:

    • anti-HCV neg --> no infection

    • anti-HCV pos --> HCV-PCR pos --> active HCV-infection with viremia

    • anti-HCV pos --> HCV-PCR neg --> no active HCV infection (interpretation: historic infection, false positive, follow-up HCV-PCR testing required)

  • Hepatitis D/E virus:

    • anti-HDV/anti-HEV: IgM and IgG

    • PCR to detect virus in serum/stool

  • Hepatitis G virus (Pegivirus):

    • PCR to detect virus

Treatment

1. Hepatitis A virus: [4sg]

   • Prophylactic vaccination, sanitation, and strict personal hygiene

   • No antiviral therapy is available

   • Supportive treatment due to risk of dehydration and acute liver failure

2. Hepatitis B virus:

   • Prophylactic vaccination

   • Acute hepatitis:

     • Supportive treatment

     • If acute liver failure (INR >1.5, bilirubin >10 mg/dL), protracted course >4 weeks or immunocompromised: nucleoside or nucleotide analogs 

   • Chronic hepatitis:

     • Pegylated interferon α for 48 weeks and lifelong nucleoside/nucleotide analog

     • Liver failure/cancer: Liver transplantation + Hepatitis B immune globulin (HBIG)

3. Hepatitis C virus:

   • Antiviral therapy can cure >95%:

     • Glecaprevir 300 mg / pibrentasvir 120 mg for 8 weeks

     • Sofosbuvir 400 mg / velpatasvir 100 mg for 12 weeks

   • Chronic hepatitis:

     • Eradication therapy with the same regimen as in acute HCV

     • Decompensated cirrhosis/cancer --> Liver transplantation

4. Hepatitis D/E/G virus:

   • HBV/HDV coinfection: pegylated interferon (PEG-IFN)

   • HEV: Supportive

   • HGV: No recommendation

5. Complications:

   • Hepatic encephalopathy: oral lactulose, rifaximin

   • Gastrointestinal bleeding: Endoscopy with sclerotherapy or band ligation, PPI, somatostatin/octreotide, antibiotics, transjugular intrahepatic portosystemic shunt (TIPS)

   • Ascites: restriction of dietary sodium intake of 2000 mg daily, oral diuretic agents (spironolactone and furosemide), paracentesis if severely symptomatic

   • Spontaneous bacterial peritonitis: intravenous antibiotics

   • Hepatocellular carcinoma: radiofrequency ablation, transarterial chemoembolization, systemic chemotherapy, surgical resection, liver transplantation

Differential diagnoses

Acute pancreatitis, Alcoholic liver disease, Aortic dissection, Autoimmune hepatitis, Budd-Chiari syndrome, Celiac disease, Cholangitis, Cholecystitis, Cholelithiasis, Drug-induced liver injury, Gastroenteritis, Gastrointestinal obstruction, Hepatocellular carcinoma, Internal hemorrhage, Intussusception, Liver abscess, Pancreatic cancer, Primary biliary cirrhosis, Primary sclerosing cholangitis, Ruptured aortic aneurysm, Systemic lupus erythematosus, Ulcerative colitis, Ulcer disease