What are the differential diagnoses for a patient presenting with vomiting, diarrhea, and jaundice, considering potential underlying liver disease or gastrointestinal disorders?

Differential Diagnoses for Vomiting, Diarrhea, and Jaundice

The triad of vomiting, diarrhea, and jaundice most commonly indicates acute viral hepatitis, severe bacterial sepsis with hepatic involvement, or drug-induced liver injury, and requires immediate evaluation of liver enzymes, bilirubin fractionation, and infectious workup to guide urgent management. 1

Immediate Life-Threatening Considerations

Infectious Causes with Hepatic Involvement

• Severe bacterial sepsis presents with jaundice due to hepatic hypoperfusion and cholestasis, often accompanied by GI symptoms and requires immediate blood cultures and broad-spectrum antibiotics 1
• Leptospirosis characteristically causes elevated transaminases with prominent GI symptoms (vomiting, diarrhea) and jaundice, particularly in patients with water exposure or animal contact 1
• Viral hepatitis (A, B, E) presents with prodromal GI symptoms (nausea, vomiting, diarrhea) followed by jaundice, with markedly elevated transaminases typically >500 U/L 1
• COVID-19 with hepatic manifestations can present with diarrhea (8.6-18.6%), vomiting (4.3-17.4%), and elevated bilirubin (25-35% of cases), though jaundice is less common 2

Hepatobiliary Emergencies

• Acute cholangitis from biliary obstruction causes jaundice with vomiting and can progress to septic shock; look for Charcot's triad (fever, jaundice, right upper quadrant pain) 3
• Acute hepatic failure from any cause presents with jaundice, GI symptoms, and requires assessment of synthetic function (INR, albumin) and mental status changes 3

Metabolic and Endocrine Causes

Pregnancy-Related

• Hyperemesis gravidarum causes intractable vomiting with weight loss >5% and can produce jaundice with bilirubin up to 7.1 mg/dL and ALT as high as 676 U/L in severe cases 4
• This diagnosis requires first-trimester pregnancy, exclusion of other hepatobiliary diseases, and often coexists with gestational thyrotoxicosis 4

Diabetic Complications

• Diabetic gastroparesis causes nausea, vomiting, and diarrhea but does not typically cause jaundice unless complicated by nonalcoholic steatohepatitis 5
• Consider if patient has diabetes with poor glycemic control and symptoms of early satiety, postprandial fullness, and bloating 5

Drug-Induced and Toxic Causes

Medication-Related Hepatotoxicity

• Lopinavir/ritonavir causes diarrhea (4-11%), nausea/vomiting (5-28%), and jaundice (6% in treatment groups) with elevated liver enzymes 2
• Favipiravir produces jaundice in 2.9-7.76% of patients along with diarrhea and digestive tract reactions 2
• Any hepatotoxic medication can produce this triad; obtain detailed medication history including over-the-counter drugs, herbal supplements, and recent antibiotic use 1

Pattern Recognition by Liver Function Test Profile

Hepatocellular Pattern (Elevated Transaminases Predominate)

• AST and ALT >500 U/L: Viral hepatitis, drug-induced liver injury, ischemic hepatitis 1
• AST:ALT ratio ~3:1: Alcoholic hepatitis, though this typically presents with less prominent diarrhea 6
• Associated conditions: Mononucleosis syndromes, legionnaires' disease, typhoid fever, toxic shock syndrome 1

Cholestatic Pattern (Elevated Alkaline Phosphatase and Bilirubin)

• Predominant bilirubin elevation: Clostridial infections, severe bacterial sepsis, relapsing fever (borreliosis) 1
• Predominant alkaline phosphatase: Q fever, secondary/tertiary syphilis, hepatic candidiasis 1

Critical Diagnostic Algorithm

First-Line Laboratory Assessment

• Liver function tests with fractionated bilirubin: Distinguish conjugated (hepatobiliary) from unconjugated (hemolytic) hyperbilirubinemia 3
• Complete blood count: Assess for hemolysis, infection, or sepsis 7
• Inflammatory markers (CRP, ESR): Elevated in infectious and inflammatory causes 8
• Blood cultures: Mandatory if fever or sepsis suspected 1

Second-Line Testing Based on Initial Results

• Viral hepatitis serologies (anti-HAV IgM, HBsAg, anti-HCV, anti-HEV IgM) if transaminases >500 U/L 1
• Right upper quadrant ultrasound: Evaluate for biliary obstruction, cholecystitis, or hepatic parenchymal disease 3
• Pregnancy test: Essential in all women of childbearing age given hyperemesis gravidarum as potential cause 4

Common Pitfalls to Avoid

• Do not assume functional GI disease when jaundice is present; this always indicates organic pathology requiring investigation 8, 7
• Do not delay antibiotics in patients with fever, jaundice, and GI symptoms while awaiting imaging, as this may represent cholangitis or sepsis 3
• Do not overlook medication history: Many drugs cause hepatotoxicity with GI prodrome, and early discontinuation improves outcomes 2
• Do not miss pregnancy: Hyperemesis gravidarum with jaundice requires supportive care but has favorable outcomes with appropriate management 4

Severity Indicators Requiring Hospitalization

• AST >273 U/L or ALT >108 U/L with GI symptoms indicates severe liver injury requiring inpatient monitoring 6
• AST:ALT ratio of 3:1 suggests severe hepatocellular injury (alcoholic hepatitis or ischemic injury) needing close observation 6
• Elevated bilirubin with abdominal pain, nausea, and vomiting has been associated with higher admission risk and requires serial liver function monitoring 9, 6