What to do in a 2-week-old female with persistent fever, tachycardia, and rhinovirus-positive status, presenting with elevated liver enzymes that have been increasing over the past 2 days?

Immediate Sepsis Workup and Supportive Care in a 2-Week-Old with Rising Transaminases

This 2-week-old with persistent fever, tachycardia, rhinovirus positivity, and rising liver enzymes requires urgent evaluation for bacterial sepsis and other life-threatening neonatal infections, as rhinovirus alone rarely causes significant hepatic injury in this age group. 1, 2

Critical Initial Assessment

Immediate actions:

• Obtain blood culture, complete blood count with differential, comprehensive metabolic panel including total and direct bilirubin, albumin, and coagulation studies (PT/INR) to assess synthetic liver function 1, 2
• Check platelet count urgently—thrombocytopenia with elevated liver enzymes in a febrile neonate raises concern for disseminated intravascular coagulation (DIC), sepsis, or viral infections beyond rhinovirus 3
• Perform lumbar puncture if not contraindicated by coagulopathy or thrombocytopenia to rule out meningitis 3
• Obtain abdominal ultrasound to assess liver parenchyma, biliary tract patency, and exclude structural abnormalities 2

Expanded Infectious Workup

Beyond rhinovirus, consider:

• Herpes simplex virus (HSV) PCR from blood and CSF—HSV can present with fever, elevated transaminases, and can be life-threatening in neonates even without characteristic vesicular rash 1, 2
• Enterovirus PCR (rhinovirus is an enterovirus, but other enteroviruses like coxsackievirus and echovirus can cause severe neonatal hepatitis) 1
• Cytomegalovirus (CMV) PCR and urine culture—congenital or perinatal CMV can cause hepatitis 1
• Bacterial cultures (blood, urine, CSF) to rule out bacterial sepsis, which commonly causes secondary hepatic dysfunction 2, 3
• Consider adenovirus PCR if hepatitis is severe, as adenovirus can cause fulminant hepatic failure in infants 1

Pattern Recognition and Severity Assessment

Determine the pattern of liver injury:

• If ALT and AST are predominantly elevated (hepatocellular pattern), this suggests direct hepatocyte injury from infection, metabolic disease, or ischemia 1, 2
• If alkaline phosphatase is disproportionately elevated (cholestatic pattern), consider biliary obstruction or neonatal cholestasis 1, 4
• Assess severity: mild-moderate elevation is <3× upper limit of normal (ULN), severe is >3× ULN, very severe is >5× ULN 2

Monitor for signs of acute liver failure:

• Rising INR or prolonged PT despite vitamin K administration indicates synthetic dysfunction and warrants immediate pediatric hepatology consultation 1, 2
• Hypoglycemia, hypoalbuminemia, or rising bilirubin (particularly direct/conjugated bilirubin >2× ULN) are concerning 2
• Development of encephalopathy (irritability, lethargy, poor feeding) in the context of liver dysfunction is ominous 2

Metabolic and Genetic Considerations

In a 2-week-old with unexplained hepatitis, consider:

• Galactosemia—check urine reducing substances and red blood cell galactose-1-phosphate uridyltransferase activity; discontinue lactose-containing feeds immediately if suspected 1
• Tyrosinemia type 1—check plasma amino acids and urine succinylacetone 1
• Neonatal hemochromatosis—check ferritin and consider MRI if severe hepatic dysfunction 1
• Mitochondrial disorders—check lactate, ammonia, and consider expanded metabolic screening 1

Management Algorithm

Empiric antimicrobial therapy while awaiting cultures:

• Initiate broad-spectrum antibiotics (ampicillin plus gentamicin or cefotaxime) to cover bacterial sepsis 2, 3
• Add acyclovir 60 mg/kg/day divided every 8 hours IV empirically for possible HSV until HSV PCR results return negative, as HSV hepatitis is rapidly progressive and fatal if untreated 1, 2

Supportive care:

• Maintain euglycemia with IV dextrose—neonates with hepatic dysfunction are at high risk for hypoglycemia 2
• Correct coagulopathy with vitamin K 1 mg IV/IM if INR elevated; consider fresh frozen plasma if active bleeding or INR >1.5 with planned procedures 2, 3
• Transfuse platelets if count <50×10⁹/L and invasive procedures planned, or <10-20×10⁹/L with active bleeding 3
• Avoid hepatotoxic medications 2

Monitoring frequency:

• Repeat liver enzymes, bilirubin, INR, and platelet count every 12-24 hours initially to establish trend (increasing, stable, or decreasing) 1, 2
• If enzymes continue rising or ALT >5× ULN develops, increase monitoring to every 3 days 2

Urgent Referral Criteria

Immediate pediatric hepatology and infectious disease consultation if:

• ALT >8× ULN or rising despite supportive care 2
• Evidence of synthetic dysfunction (INR >1.5, albumin <3.0 g/dL) 1, 2
• Total bilirubin >2× ULN with ALT >3× ULN (meets Hy's Law criteria for severe drug-induced liver injury, though adapted here for any severe hepatocellular injury) 2
• Clinical deterioration with encephalopathy, refractory hypoglycemia, or worsening coagulopathy 2

Transfer to tertiary care center with pediatric intensive care and potential liver transplant capability if acute liver failure develops 2

Common Pitfalls to Avoid

• Do not attribute all symptoms to rhinovirus—rhinovirus typically causes mild upper respiratory symptoms and does not commonly cause significant hepatitis in immunocompetent neonates 1, 2
• Do not delay HSV treatment—neonatal HSV can present without skin lesions in up to 20% of cases, and hepatitis can be the predominant manifestation; empiric acyclovir should be started immediately 1
• Do not overlook metabolic diseases—galactosemia and tyrosinemia can present in the first weeks of life with hepatitis and are medical emergencies requiring specific dietary interventions 1
• Do not wait for serologic confirmation—in neonates, maternal antibodies can interfere with serologic testing; PCR-based diagnostics are preferred for acute infections 1