Author:
Duncan K.Wilson
Christopher T.Richards
Description
- Inflammation of the liver owing to infectious, toxic, and autoimmune disorders:
- Progression from hepatocellular injury (hepatitis) to scarring (cirrhosis)
Etiology
- Unknown etiology in 5-10% of acute and chronic hepatitis cases and up to 50% in fulminant hepatic failure (FHF)
- Infection is the most common etiology of acute hepatitis
- Hepatitis A (HAV):
- Transmission: Fecal-oral
- Incubation period: 15-45 d
- FHF in 0.1%
- No chronic phase:
- 10% will have a relapsing course over months
- Hepatitis B (HBV):
- Transmission: Percutaneous exposure to bodily fluids, sexual contact, perinatal
- Incubation period: 30-180 d
- 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:15-160 d
- 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: 30-180 d
- 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: 14-60 d
- FHF in 1-2% of previously healthy adults, 10-20% in pregnant patients
- 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:
- Medication and toxin induced:
- Acetaminophen toxicity is the most common cause of acute liver failure in the western world
- Dose-dependent (e.g., acetaminophen)
- Idiosyncratic (e.g., isoniazid)
- Autoimmune hepatitis:
- Cell-mediated immunologic attack on hepatocytes
- May be associated with a personal or family history of autoimmune disease
- Tends to affect young to middle-aged women
- Nonalcoholic fatty liver disease:
- Most common form of chronic liver disease in the U.S., affecting 25% of adults
- Associated with steatohepatitis and rarely cirrhosis
- Inherited liver disease:
- Wilson disease
- Hemochromatosis
- α-1 antitrypsin deficiency
Pediatric Considerations |
- Vast majority of cases are caused by HAV
- Perinatal HBV infection develops into chronic disease 90% of the time
|
Pregnancy Prophylaxis |
- 20% case fatality for HEV during pregnancy
- Acute fatty liver of pregnancy (AFLP):
- Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome
- Immunoprophylaxis is safe during pregnancy
|
Signs and Symptoms
- Often asymptomatic
- 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
History
- Travel history
- Immunization history
- High-risk sexual practices, particularly men who have sex with men (MSM)
- History of IV drug use (IVDU)
- Medications including OTC med and herbal supplements
- Alcohol use
- Family history of liver disease
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
- Hepatic encephalopathy (HE)
- 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
Diagnostic 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
- Elevation of conjugated bilirubin due to decreased excretion
- Lipase may indicate pancreatic or biliary etiology
- PT/PTT/INR and albumin:
- Measure of synthetic function of liver
- Prolonged INR reflects more severe injury
- Ammonia level:
- For patients with encephalopathy
- Degree of elevation does not correlate with degree of HE
- 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 for cerebral edema and evaluate for other causes of altered mental status
- RUQ US to evaluate for biliary obstruction
- Liver US w Doppler to evaluate for vascular occlusion
Differential Diagnosis
- Viral hepatitis
- Toxic hepatitis
- Nonalcoholic steatohepatitis
- Autoimmune hepatitis
- Cholecystitis and cholangitis
- Reye syndrome
- Liver abscess
- Wilson disease
- Hemochromatosis
- Alpha-1 antitrypsin deficiency
- Heat stroke
- Fitz-Hugh-Curtis syndrome
- Ischemic hepatitis (“shock liver”)
- Congestive heart failure with congestive hepatopathy
- Budd-Chiari syndrome
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
- Prefer medications not metabolized by liver:
- Correct coagulopathy if active bleeding
- N-acetylcysteine (NAC) for acetaminophen-induced hepatitis and consider for FHF of any etiology
- Steroids and pentoxyfylline are not helpful for severe alcoholic hepatitis and are not recommended
- 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 d of exposure
- HBV vaccine 1 mL (peds: 0.5 mL) IM
- No effective immunoprophylaxis for HCV or HDV
- HEV vaccine not available in the U.S.
Medication
- Cholestyramine: 4 g PO 2-4 times per day for pruritus
- Metoclopramide: 10 mg IV/IM q6-8h, 10-30 mg PO q.i.d
- NAC 140 mg/kg IV loading dose
- Ondansetron 4 mg IV
- Thiamine: 100 mg (peds: 50 mg) IV/IM/PO:
- Prior to glucose if malnourished
- Ursodeoxycholic acid: 3 mg/kg t.i.d
- Vitamin K 10 mg IV/PO
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
- Age >50
- For acetaminophen toxicity, transfer to a transplant center is suggested if:
- Arterial pH <7.30 OR
- INR > 6.5 and
- Creatinine > 3.4 mg/dL and
- Grade III/IV HE
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
- BernalW, WendonJ. Acute liver failure . N Engl J Med. 2013;369(26):2525-2534.
- FargoMV, GroganSP, SaguilA. Evaluation of jaundice in adults . Am Fam Physician. 2017; 95(3):164-168.
- KarnsakulW, SchwarzK. Hepatitis B, and C . Pediatr Clin North Am. 2017;64(3):641-658.
- ThurszMR, RichardsonP, AllisonM, et al. Prednisolone or pentoxifylline for alcoholic hepatitis . N Engl J Med. 2015;372:1619-1628.
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