DESCRIPTION

• Inflammation of the liver owing to infectious, toxic, and autoimmune disorders
  • Progression from hepatocellular injury (hepatitis) to scarring (cirrhosis)
• Infectious causes are the most common

ETIOLOGY

• Unknown etiology in 5–10% of acute and chronic hepatitis cases and up to 50% in fulminant hepatic failure (FHF)
• Hepatitis A (HAV):
  • Transmission: Fecal–oral
  • Incubation period: 2–7 wk
  • FHF in 0.1%
  • No chronic phase
    • 10% will have a relapsing course over months
• Hepatitis B (HBV):
  • Transmission: Mucous membrane, percutaneous exposure to bodily fluids, perinatal
  • Incubation period: 8–22 wk
  • Subclinical in 70%
  • FHF in 1%
  • Risk of chronic hepatitis increased with age at infection and comorbidities:
    • Neonatal: > 90%
    • Infant: 50%
    • Child: 20%
    • Immunocompetent adult: 1–5%
    • Immunocompromised adult: 50%
  • Risk of cirrhosis, hepatocellular carcinoma
• Hepatitis C (HCV):
  • Transmission: Blood >> sexual and perinatal
  • Incubation period: 6–10 wk
  • FHF rare
  • 80% progress to chronic disease
  • Risk of cirrhosis, hepatocellular carcinoma
• Hepatitis D (HDV):
  • HDV can be transmitted only in the presence of HBV infection
    • 2 patterns of infection: Simultaneous infection with HBV and HDV or HDV superinfection in an individual with chronic HBV
  • Same transmission as HBV
  • Incubation period: 3–7 wk
  • FHF in 3%
  • 5% progress to chronic disease
  • Risk of cirrhosis 3 times higher in HDV-infected individual compared with HBV infection alone
• Hepatitis E (HEV):
  • Most common cause of acute hepatitis and jaundice worldwide
  • Rarely found outside developing countries
  • Typically seen as outbreaks
  • Transmission: Fecal–oral, waterborne, foodborne
  • Incubation period: 3–8 wk
  • FHF in 10%
  • Chronic infection almost exclusively in immunocompromised persons
• Alcoholic hepatitis:
  • Associated with > 14 drinks/wk in women and > 21 drinks/wk in men
  • Sequelae of chronic use:
    • Hepatic steatosis in 90–100%
    • Hepatitis in 10–35%
    • Cirrhosis in 5–15%
  • Increased association with chronic viral hepatitis
  • Maddrey discriminant function (MDF) ≥32 associated with only 50–65% survival
    • MDF = 4.6 × [prolongation of PT above control](s) + serum bilirubin(mg/dL)
• Abscess-induced hepatitis:
  • Entamoeba histolytica, pyogenic
• Secondary hepatitis viruses:
  • CMV, EBV, HSV, HIV
• Medication and toxin induced
• Autoimmune hepatitis:
  • Display concurrent stigmata of autoimmune disease

Pediatric Considerations

• Vast majority of cases are caused by HAV
• Perinatal HBV infection develops into chronic disease 90% of the time

Pregnancy Considerations

• 20% case fatality for HEV during pregnancy.
• Acute fatty liver of pregnancy (AFLP):
  • May progress to DIC
• Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome
• Immunoprophylaxis is safe during pregnancy

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

• Often asymptomatic
• Preicteric phase:
  • Often misdiagnosed as a nonspecific viral syndrome or gastroenteritis
• Icteric phase:
  • Present in 70% of HAV, 30% of HBV, and 20% of HCV
• FHF:
  • Coagulopathy
  • Encephalopathy
  • Cerebral edema

History

• Preicteric phase:
  • Fever, chills
  • Malaise
  • Nausea, vomiting, anorexia
  • Arthralgia
  • Aversion to smoking
• Icteric phase:
  • Jaundice
  • Dark urine
  • Light stools
  • Pruritus
  • Rash
  • Right upper quadrant pain
• FHF:
  • Bleeding
  • Altered mental status

Physical Exam

• Preicteric phase:
  • Fever
  • Arthritis
  • Dehydration
• Icteric phase:
  • Fever
  • Icterus of skin, sclerae, mucous membranes, and tympanic membranes
  • Nonspecific maculopapular or urticarial rash
  • Dehydration
  • Tender hepatomegaly
• FHF:
  • Bruising
  • Disorientation
  • Asterixis

ESSENTIAL WORKUP

• Detailed history of risk factors for hepatitis, including toxic exposure and drug use
• Viral serologies are the mainstay of diagnosis of viral causes

DIAGNOSIS TESTS & INTERPRETATION

Lab

• CBC with differential
• Basic metabolic panel:
  • Azotemia with hepatorenal syndrome in FHF
  • Hypoglycemia with severe liver damage
  • Hyponatremia
• LFTs:
  • Elevation in transaminases reflects hepatocellular injury
  • Degree of elevation does not always correlate with severity
  • If alkaline phosphatase more than 4 times normal, consider primary cholestatic process rather than viral hepatitis.
  • Mild to moderate elevation of conjugated bilirubin due to decreased excretion
• Amylase, lipase may indicate pancreatic or biliary etiology
• PT/PTT/INR, albumin
  • Measure of synthetic function of liver
  • Prolonged INR reflects more severe injury
• Ammonia level:
  • For patients with altered mental status
• Viral serologies:
  • HAV:
    • Anti-HAV IgM: Acute infection
    • Anti-HAV IgG: Previous exposure, immunity
  • HBV:
    • HBsAg: Acute infection (appears before symptoms), chronic infection
    • Anti-HBs: Past infection, carrier state, postimmunization
    • Anti-HBc IgM: Acute infection
    • Anti-HBc IgG: Past infection, chronic infection, carrier state
    • HBeAg: Acute infection, some chronic states
    • Anti-HBe: Past infection, chronic infection, carrier state
    • Postimmunization: Anti-HBs only
  • HCV:
    • Anti-HCV: Acute infection, chronic infections, first-line test
    • HCV RNA: Acute infection, chronic infections; confirmatory
  • HDV: Anti-HDV or viral RNA, not routine
  • HEV:
    • Anti-HEV IgM: Acute infection, detectable for only 3–12 mo
    • Anti-HEV IgG: Persists for years, if not for life
• α-fetoprotein:
  • For chronic HBV or HCV to evaluate for hepatocellular carcinoma
• Monospot: For EBV
• Urinalysis for bilirubin

Imaging

• Head CT to evaluate hepatic encephalopathy
• RUQ US to evaluate for biliary obstruction

DIFFERENTIAL DIAGNOSIS

• Nonalcoholic fatty liver disease
• Cholecystitis and cholangitis
• Reye syndrome
• Liver abscess
• Wilson disease
• Heat stroke
• Fitz-Hugh—Curtis syndrome
• Ischemic hepatitis ("shock liver")
• Congestive heart failure
• Hemochromatosis
• Budd–Chiari syndrome

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

INITIAL STABILIZATION/THERAPY

ABCs and IV fluid resuscitation for FHF and severe hepatic encephalopathy.

ED TREATMENT/PROCEDURES

• Treat hypovolemia judiciously with isotonic fluids
• Correct electrolyte imbalance
• Treat vomiting with ondansetron and metoclopramide
• Avoid hepatotoxic agents: Acetaminophen, alcohol, phenothiazines
• Avoid medications metabolized by liver
  • Propofol for sedation preferred
  • Fentanyl for pain preferred
• Correct coagulopathy if active bleeding.
• N-acetylcystine (NAC) for acetaminophen-induced hepatitis and consider for FHF
• Consider steroids for severe acute alcoholic hepatitis
• Ursodeoxycholic acid or cholestyramine for cholestasis-induced itching
• Paracentesis for tense ascites leading to respiratory compromise
• Antidotes and activated charcoal for select ingestions
• Postexposure prophylaxis (PEP):
  • HAV:
    • HAV IG 0.02 mL/kg IM within 2 wk of exposure
    • HAV vaccine 1 mL (peds: 0.5 mL) IM
  • HBV:
    • HBV IG 0.06 mL/kg IM within 7 days of exposure
    • HBV vaccine 1 mL (peds: 0.5 mL) IM
  • No effective immunoprophylaxis for HCV or HDV
  • HEV vaccine not available in US

MEDICATION

• Cholestyramine: 4 g PO 2–4 times per day for pruritus
• Metoclopramide: 10 mg IV/IM q6–8h, 10–30 mg PO QID
• NAC 140 mg/kg IV loading dose
• Ondansetron 4 mg IV
• Prednisone 40 mg/d PO
• Thiamine: 100 mg (peds: 50 mg) IV/IM/PO:
  • Prior to glucose if malnutritioned
• Ursodeoxycholic acid: 3 mg/kg TID
• Vitamin K 10mg IV/PO

[Outline]

• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

• Intractable vomiting, dehydration, or electrolyte imbalance not responding to ED treatment
• ICU and consider transfer to transplant center for FHF and acute hepatitis with evidence of significant liver dysfunction:
  • PT > 50% of normal or INR > 1.5
  • Bilirubin > 20 mg/dL
  • Hypoglycemia
  • Albumin < 2.5 g/dL
• Hepatic encephalopathy
• Pregnancy
• Immunocompromised host
• Possibility of toxic hepatitis
• Age > 50

Discharge Criteria

• Normalized electrolytes
• PO tolerance
• Mild hepatic impairment

Issues for Referral

• Hepatology, gastroenterology, and/or infectious disease follow-up for further serologic diagnosis and definitive treatment
• Alcoholics anonymous referral and social work referral for alcohol-related disease

FOLLOW-UP RECOMMENDATIONS

• Strict personal hygiene instructions
• Avoid acetaminophen and alcohol
• Avoid prolonged physical exertion

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• Acute hepatitis is often misdiagnosed as a nonspecific viral syndrome—screen with urinalysis or serum LFTs
• ED treatment is primarily supportive
• Ask detailed social and travel history
• Early transfer to transplant center for FHF
• Counsel patient on prevention – vaccinations and personal hygiene precautions
• Maintain high index of suspicion for AFLP and HELLP in pregnant patients with compatible symptoms

ICD9

• 070.1 Viral hepatitis A without mention of hepatic coma
• 070.30 Viral hepatitis B without mention of hepatic coma, acute or unspecified, without mention of hepatitis delta
• 573.3 Hepatitis, unspecified

ICD10

• B15.9 Hepatitis A without hepatic coma
• B19.10 Unspecified viral hepatitis B without hepatic coma
• K75.9 Inflammatory liver disease, unspecified

[Outline]

• ICD9
• ICD10

• Falade-Nwulia O, Seaberg EC, Rinaldo CR, et al. Comparative risk of liver-related mortality from chronic hepatitis B versus chronic hepatitis C virus infection. Clin Infect Dis. 2012;55(4):507–513.
• Greenberger NJ, Blumberg RS, Burakoff R, eds. Current Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy. 2nd ed. McGraw-Hill; 2012.
• Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012;367:1237–1244.
• Sundaram V, Shaikh OS. Acute liver failure: Current practice and recent advances. Gastroenterol Clin North Am. 2011;40(3):523–539.

See Also (Topic, Algorithm, Electronic Media Element)

• Acetaminophen Poisoning
• Ascites
• Cirrhosis
• Hepatic Encephalopathy
• Hepatorenal Syndrome
• Jaundice
• Mushroom Poisoning

We wish to acknowledge the previous authors of this chapter for their contributions on this topic: Michael Schmidt, Amer Aldeen, and Lucas Roseire.

Jason Koob

Christopher T. Richards