Leptospirosis, a zoonotic infection prevalent in Pakistan, presents diverse clinical manifestations ranging from mild flu-like symptoms to severe multiorgan failure known as Weil\'s disease. This case study reports on a 24-year-old woman with leptospirosis complicated by acute kidney injury and hyperbilirubinemia, unresponsive to standard therapies. Despite initial treatment with antibiotics and hemodialysis, her condition deteriorated. Following a single session of plasmapheresis, marked clinical and laboratory improvements were observed. Notably, plasma exchange effectively reduced bilirubin levels, underscoring its potential benefit in severe leptospirosis. This case highlights the role of plasmapheresis as rescue therapy in critically ill patients, demonstrating significant outcomes in cases resistant to conventional management. Further research is warranted to refine guidelines on the optimal timing and frequency of plasma exchange in such settings.

A 70-year-old female, diagnosed with mitochondrial diabetes mellitus (MDM) showing previously a point mutation at mitochondrial DNA 3316G>A, noticed urinary tract infection and diabetic gangrene of the foot with Gram-negative Bacteroides fragilis bacteremia, followed by aggressive jaundice with high serum level of direct bilirubin. She died two months after the symptom onset. At autopsy, multiple foci of bacteremia-induced hemorrhagic infarction were observed in the congestive bilateral lungs, whereas the cholestatic liver revealed no overt gross cholangiectasis. Microscopic findings characteristically showed many bile thrombi in the biliary canaliculi of hepatic lobules without any evidence of severe shock liver. Finally, we diagnosed it exclusively as sepsis-associated cholestasis due to the marked elevation of Gram-negative bacteria-derived endotoxins and inflammatory cytokines. We propose that these unique liver features in our MDM case might be one of the new clues to unveil its enigmatic etiology.

Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with no significant signs of hepatic impairment. The index pregnancy was complicated by Rhesus factor immunization with anti-D antibodies present in maternal serum, which caused fetal anemia requiring intrauterine blood transfusions. Complementary tests demonstrated Rhesus D alloimmunization as the sole cause of cholestasis. To the best of our knowledge, this is the first study to describe such elevated direct bilirubin concentrations caused by HDFN.

UNASSIGNED: Reference guidelines for neonatal conjugated hyperbilirubinemia (cholestasis) management use a uniform approach regardless of gestational age (GA). We hypothesize that the clinical pattern of neonatal cholestasis is tightly related to GA. The aim of this study was to describe the effects of GA on neonatal cholestasis.
UNASSIGNED: A retrospective 4-year cohort study in a 70-bed neonatal care unit. Neonates with conjugated bilirubin≥34.2μmol/L (2 mg/dL) were identified. The incidence, clinical characteristics, etiology, treatment, and prognosis were compared between infants <32 and≥32 weeks GA.
UNASSIGNED: Overall incidence of cholestasis was 4% (125/3402). It was >5 times higher and the mean duration was >1.5 times longer in neonates <32 weeks GA (10% versus 1.8%, p <0.01 and 49 versus 31 days, p <0.01, respectively). The onset of cholestasis was later in neonates <32 weeks (22 versus 10 days of life, p <0.001). This later onset of cholestasis was associated with parenteral nutrition, whereas the earlier onset was associated with other causes. Treatment using fish oil lipids was more frequently administrated to infants <32 weeks GA, whereas Ursodeoxycholic acid was administrated more frequently in≥32 weeks GA. Cholestasis resolved during hospitalization in 73% of <32 versus 38% in≥32 weeks GA infants (p <0.01).
UNASSIGNED: The incidence, clinical presentation, etiology, treatment, and clinical evolution of neonatal cholestasis were all significantly affected by GA. Our results support the use of a GA-oriented approach for the management of neonatal cholestasis.

Hepatic injuries attributable to terbinafine usage are a well-documented yet infrequent phenomenon. This case study details the clinical presentation and management of a 70-year-old Hispanic female, with no previous medical history, subsequently hospitalized for progressive jaundice, right upper quadrant abdominal discomfort, and worsening pruritus. A comprehensive review of her prior records revealed a recent terbinafine prescription for onychomycosis, which she took consistently for five weeks and then self-discontinued four weeks before her current admission. Laboratory tests on admission revealed a cholestatic pattern of liver injury, evident by transaminitis and conjugated hyperbilirubinemia. The R factor used to determine whether a liver injury is hepatocellular or cholestatic was 0.9. Further diagnostic imaging, including abdominal ultrasound, CT of the abdomen, and magnetic resonance cholangiopancreatography, failed to disclose an obstructive pathology, revealing only cholelithiasis and chronic cholecystitis. Therapeutically, the patient was initiated on hydroxyzine to address symptoms of pruritus, and then subsequently underwent a liver biopsy. Histopathologic findings from the biopsy revealed benign hepatic parenchyma demonstrating focal canalicular cholestasis, mild chronic inflammation involving select portal tracts, and chronic lobular inflammation, suggesting terbinafine-induced hepatotoxicity. This case highlights the challenges of diagnosing terbinafine-induced liver injury, emphasizing the need for a high index of clinical suspicion and recognizing the potential for prolonged symptomatic manifestation after drug discontinuation. This article provides valuable insights into the complexities inherent in such diagnoses and significantly enriches a medical provider\'s approach to diagnosing and treating unexplained liver injuries.

BACKGROUND: Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality.
METHODS: This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020. Patient- and surgery-specific data were abstracted from local registry data and review of the medical record. Conjugated hyperbilirubinemia was defined as perioperative maximum conjugated bilirubin level > 1 mg/dL. The primary outcome was in-hospital mortality. Survival analysis was conducted using the Kaplan-Meier survival function.
RESULTS: Conjugated hyperbilirubinemia occurred in 8.5% of patients during the study period. Neonates with conjugated hyperbilirubinemia were more likely to be of younger gestational age, lower birth weight, and non-Caucasian race (all p < 0.001). Patients with conjugated hyperbilirubinemia were more likely to have chromosomal and non-cardiac anomalies and require ECMO pre-operatively. In-hospital mortality among patients with conjugated hyperbilirubinemia was increased compared to those without (odds ratio 5.4). Post-operative complications including mechanical circulatory support, reoperation, prolonged ventilator dependence, and multi-system organ failure were more common with conjugated hyperbilirubinemia (all p < 0.04). Patients with higher levels of conjugated bilirubin had worst intermediate-term survival, with patients in the highest conjugated bilirubin group (>10 mg/dL) having a 1-year survival of only 6%.
CONCLUSIONS: Conjugated hyperbilirubinemia is associated with post-operative complications and worse survival following neonatal heart surgery. Cholestasis is more common in patients with chromosomal abnormalities and non-cardiac anomalies, but the underlying mechanisms have not been delineated.

UNASSIGNED: Cholestatic disorders are a significant cause of morbidity and mortality in infants. Characterization of these disorders and differentiating biliary atresia (BA) from other causes of intrahepatic cholestasis is an age-old problem.
UNASSIGNED: To study the spectrum of different infantile cholestatic disorders in our population, to differentiate BA from other causes of neonatal cholestasis (NC) on a liver biopsy, and validation of the available scoring system for the characterization of these disorders.
UNASSIGNED: This is an observational cross-sectional study performed over a period of 3 years between 2018 and 2021, done on neonates and infants presenting with cholestatic jaundice. The changes on liver biopsy were evaluated by different histological parameters and available scoring systems to differentiate BA from non-BA causes. Correlation with clinical, biochemical, and imaging findings was done in all cases.
UNASSIGNED: This study included 87 cases of NC, of which BA comprised 28 cases (32%), whereas idiopathic neonatal hepatitis (INH) comprised only 12 cases (14%). Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), neoductular bile plugs (P < 0.001) and bile ductular proliferation (P < 0.0001) were significantly more in BA, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequent in the non-BA group. Using the Lee and Looi scoring system, a histologic score ≥7 was helpful in identifying BA with 85.7% sensitivity, 92.6% specificity, and 90.6% accuracy.
UNASSIGNED: BA is the commonest cause of NC in neonates, whereas the frequency of INH is declining. Detailed histomorphologic analysis of liver biopsy, aided with IHC, is the cornerstone for the diagnosis of these disorders.

Introduction The aim of our study was to assess the impact of intrauterine growth restriction (IUGR) and placental insufficiency (PI) on the nutritional outcomes of extremely low birth weight (ELBW) infants. Methods We conducted a six-year retrospective case-control study that included 117 ELBW infants. Of these, 58 infants had IUGR and 59 were born appropriate-for-gestational age (AGA). Infants with IUGR were further divided based on the presence or absence of PI, as determined by umbilical arterial doppler velocimetry on serial ultrasounds. Results IUGR infants with PI had the lowest enteral calorie intake at 28 days of life (DOL) (median intake- IUGR+PI: 32 vs IUGR-PI: 93 vs AGA: 110 kcal/kg/day; p-value 0.011) and at 36 weeks corrected gestational age (CGA) (median intake- IUGR+PI: 102 vs IUGR-PI: 125 vs AGA: 119 kcal/kg/day; p-value 0.012). These infants also trended towards requiring a longer duration of total parenteral nutrition (TPN) (median duration - IUGR+PI: 35 vs IUGR-PI: 25 vs AGA: 21 days; p-value 0.054) and higher incidence of conjugated hyperbilirubinemia (IUGR+PI: 43% IUGR-PI: 29% vs AGA: 16%; p-value 0.058), but these results did not reach statistical significance. Despite challenges with enteral nutrition, IUGR infants with PI showed good catch-up growth and had higher growth velocities over the first month of life, compared to AGA controls. Conclusion IUGR in the presence of PI is associated with significantly poorer enteral nutritional outcomes in ELBW infants. However, with the support of optimal parenteral nutrition these infants showed good catch-up growth.

A 42-year-old man with no relevant past medical history presented with intermittent mild icterus and no signs of chronic liver disease. Laboratory tests were notable for hyperbilirubinemia (total 7.97 mg/dL, direct 5.37 mg/dL), bilirubinuria, no signs of hemolysis, normal liver tests and lipids profile. Abdominal ultrasound was unremarkable. A panel of chronic liver diseases was negative except for increased serum (147.4 μg/dL) and urinary (179 μg/24 h) copper, with normal ceruloplasmin. No other Leipzig criteria for Wilson\'s disease were found, including a negative test for ATP7B gene mutations (by exome sequencing). Total urinary coproporphyrin was normal with predominance of isomer I (86% of total urinary coproporphyrin output). Clinical and laboratorial profile was compatible with Dubin-Johnson syndrome; however, exome sequencing and search for deletions in the ABBC2 gene (encoding MRP2) only found a heterozygous potentially pathogenic variant (c.1483A>G - p.Lys495Glu). Additional extended molecular analysis of genes implicated in bilirubin metabolism found a homozygous deletion of a region encompassing exons 4-16 of SLCO1B3 gene (encoding OATP1B3) and all SLCO1B1 exons (encoding OATP1B1), thereby establishing Rotor syndrome diagnosis. Rotor and Dubin-Johnson syndromes are rare autosomal recessive liver diseases characterized by chronic conjugated hyperbilirubinemia, caused by the absence of the hepatic function OATP1B1/B3 (leading to impaired hepatic bilirubin reuptake and storage) and MRP2 transporters (leading to impaired hepatic bilirubin excretion), respectively. We report a case of compound hereditary hyperbilirubinemia with a misleading presentation with special focus on its diagnosis, particularly the advantage of extensive unbiased genetic testing by dedicated laboratories. With this case, we aim to highlight the necessity of establishing a diagnosis, reassuring the patient, and avoiding unnecessary invasive and costly diagnostic procedures.

Biliary atresia (BA) and choledochal cysts are diseases of the intrahepatic and extrahepatic biliary tree. While their exact etiopathogeneses are not known, they should be treated promptly due to the potential for irreversible parenchymal liver disease. A diagnosis of BA may be easy or complicated, but should not be delayed. BA is always treated surgically, and performing the surgery before the age of 2 mo greatly increases its effectiveness and extends the time until the need for liver transplantation arises. While the more common types of choledochal cysts require surgical treatment, some can be treated with endoscopic retrograde cholangiopancreatography. Choledochal cysts may cause recurrent cholangitis and the potential for malignancy should not be ignored.