Clinical outcomes of surgical management for rare types of progressive familial intrahepatic cholestasis: a case series

Background Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive diseases that cause severe cholestasis, which progresses to cirrhosis and liver failure, in infancy or early childhood. We herein report the clinical outcomes of surgical management in patients with four types of PFIC. Case presentation Six patients diagnosed with PFIC who underwent surgical treatment between 1998 and 2020 at our institution were retrospectively assessed. Living-donor liver transplantation (LDLT) was performed in 5 patients with PFIC. The median age at LDLT was 4.8 (range: 1.9–11.4) years. One patient each with familial intrahepatic cholestasis 1 (FIC1) deficiency and bile salt export pump (BSEP) deficiency died after LDLT, and the four remaining patients, one each with deficiency of FIC1, BSEP, multidrug resistance protein 3 (MDR3), and tight junction protein 2 (TJP2), survived. One FIC1 deficiency recipient underwent LDLT secondary to deterioration of liver function, following infectious enteritis. Although he underwent LDLT accompanied by total external biliary diversion, the patient died because of PFIC-related complications. The other patient with FIC1 deficiency had intractable pruritus and underwent partial internal biliary diversion (PIBD) at 9.8 years of age, pruritus largely resolved after PIBD. One BSEP deficiency recipient, who had severe graft damage, experienced recurrence of cholestasis due to the development of antibodies against BSEP after LDLT, and eventually died due to graft failure. The other patient with BSEP deficiency recovered well after LDLT and there was no evidence of posttransplant recurrence of cholestasis. In contrast, recipients with MDR3 or TJP2 deficiency showed good courses and outcomes after LDLT. Conclusions Although LDLT was considered an effective treatment for PFIC, the clinical courses and outcomes after LDLT were still inadequate in patients with FIC1 and BSEP deficiency. LDLT accompanied by total biliary diversion may not be as effective for patients with FIC1 deficiency.

Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh

Background Neonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh. Results Out of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes. Conclusion BA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.