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OBJECTIVE: Biomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD. METHODS: Consecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines. RESULTS: 107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection. CONCLUSION: nCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD.
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Objective: To evaluate the coagulation status of children with decompensated chronic liver disease (DCLD) and infection and factors affecting it using thromboelastography (TEG). Methods: Coagulation status of children admitted with DCLD and infection was assessed by international normalized ratio (INR), platelet count, and TEG [reaction time (R), kinetic time (K), α-angle (AA), maximum amplitude (MA), coagulation index (CI), and lysis index (LY30)] at admission and at 7-14 days after treatment. CI < -3 represents hypocoagulable state. Clinical profile including systemic inflammatory response syndrome (SIRS), infection severity, bleeding, treatment response, and outcome were noted. Results: Thirty children (21 boys, median (IQR) age 78 [15.7-180] months) were studied prospectively. At admission, 29 (96.7%) had prolonged INR, 24 (80%) had thrombocytopenia, and 17 (56.6%) were hypocoagulable by TEG. Nine of 30 (30%) had normal TEG but deranged INR and platelets. Nineteen (63.3%) cases had SIRS, 11 (36.6%) had severe sepsis, and 8 (26.6%) had bleeding. Hypocoagulable state was common in severe sepsis than sepsis/infection (81.1% versus 42.1%; P = 0.05) and persistent (n = 4) versus recovered SIRS (n = 15, 100% versus 33%; P = 0.03). Bleeders had prolonged R-time (7.8 versus 5.4 min; P = 0.03), smaller MA (30.2 versus 47 mm; P = 0.05), and α-angle (40.4 versus 62.9; P = 0.03) but similar INR and platelets than nonbleeders. Six patients (20%) had poor in-hospital outcomes; R-time ≥8.5 min predicted mortality with high sensitivity (83%) and specificity (100%). Conclusions: Fifth-seven percent of children with DCLD and infection were hypocoagulable by TEG. Severe sepsis and persistent SIRS worsened the coagulation status. TEG identifies bleeders better than INR and platelet count. R-time ≥8.5 min predicts a poor hospital outcome.
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Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of disorders characterized by defects in bile secretion and presentation with intrahepatic cholestasis in infancy or childhood. The most common types include PFIC 1 (deficiency of FIC1 protein, ATP8B1 gene mutation), PFIC 2 (bile salt export pump deficiency, ABCB11 gene mutation), and PFIC 3 (multidrug resistance protein-3 deficiency, ABCB4 gene mutation). Mutational analysis of subjects with normal gamma-glutamyl transferase cholestasis of unknown etiology has led to the identification of newer variants of PFIC, known as PFIC 4, 5, and MYO5B related (sometimes known as PFIC 6). PFIC 4 is caused by the loss of function of tight junction protein 2 (TJP2) and PFIC 5 is due to NR1H4 mutation causing Farnesoid X receptor deficiency. MYO5B gene mutation causes microvillous inclusion disease (MVID) and is also associated with isolated cholestasis. Children with TJP2 related cholestasis (PFIC-4) have a variable spectrum of presentation. Some have a self-limiting disease, while others have progressive liver disease with an increased risk of hepatocellular carcinoma. Hence, frequent surveillance for hepatocellular carcinoma is recommended from infancy. PFIC-5 patients usually have rapidly progressive liver disease with early onset coagulopathy, high alpha-fetoprotein and ultimately require a liver transplant. Subjects with MYO5 B-related disease can present with isolated cholestasis or cholestasis with intractable diarrhea (MVID). These children are at risk of worsening cholestasis post intestinal transplant (IT) for MVID, hence combined intestinal and liver transplant or IT with biliary diversion is preferred. Immunohistochemistry can differentiate most of the variants of PFIC but confirmation requires genetic analysis.