Intravenous lipid emulsions with or without fish oil for the prevention of liver disease in VLBW neonates: A network meta-analysis.

Per the ACG 2017 abstract and the 'Elevation of Total Bilirubin Level' section (summary statements + Figure 5 + Table 6): Elevated total serum bilirubin (normal usually <1.1 mg/dl) should be FRACTIONATED into conjugated (direct) and unconjugated (indirect) fractions; fractionation is most helpful when ALT/AST and alkaline phosphatase are normal or near-normal. An elevated serum conjugated (direct) bilirubin implies hepatocellular disease or biliary obstruction IN MOST SETTINGS, in contrast to unconjugated (which is over-production/hemolysis, decreased uptake, or decreased conjugation), the guideline keeps 'in most settings' rather than stating an absolute rule. PREDOMINANT-UNCONJUGATED elevation (Fig 5, left arm): history/exam, assess transaminases and ALP, review medications, evaluate for hemolysis (haptoglobin, reticulocytes, LDH) and for Gilbert's syndrome; in an asymptomatic person with mild unconjugated hyperbilirubinemia (<4 mg/dl) with normal transaminases/ALP, no hemolysis, and no offending drug, a presumptive Gilbert's diagnosis can be made and further evaluation is not routinely necessary (Gilbert's: total almost never >6 mg/dl, usually <3; fasting/illness raises it 2-3 fold). Optional UGT1A1 genotype and workup of uncommon Table-6 causes only if persistently unexplained. PREDOMINANT-CONJUGATED elevation (Fig 5, right arm): history/exam, assess transaminases and ALP, review medications, evaluate clinically overt etiologies (sepsis, TPN, cirrhosis, biliary obstruction), and perform right-upper-quadrant ultrasound, if ductal dilatation → ERCP or MRCP; if no ductal dilatation → check AMA, ANA and SMA. Per graded Recommendations 14-15, alkaline phosphatase elevation with or without bilirubin warrants anti-mitochondrial antibody for PBC and MR cholangiography or ERCP in conjunction with IgG4 for PSC (both Strong recommendation, very low quality). Consider liver biopsy for diagnostic confirmation when the elevation is otherwise unexplained, symptomatic, worsening over time, or associated with abnormal transaminases. Two rare BENIGN inherited conjugated hyperbilirubinemias, Dubin-Johnson and Rotor, show direct bilirubin ~50% of total with all other liver tests normal including ALP and GGT; it is not necessary to distinguish them. Conjugated total bilirubin may exceed 30 mg/dl in severe liver damage (e.g., alcoholic hepatitis with cirrhosis, or advanced cirrhosis with sepsis/renal failure), and an isolated conjugated hyperbilirubinemia may follow major surgery and typically resolves.