The role of liver transplantation in COACH syndrome (Joubert syndrome with congenital hepatic fibrosis): A review of the literature.

BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension. However, only a few patients with COACH syndrome undergoing liver transplantation (LT) have been reported. MATERIALS AND METHODS: We herein report the outcomes of four children who underwent LT for COACH syndrome at our institute and review three previously reported cases to elucidate the role of LT in COACH syndrome. RESULTS: All four patients in our institute were female, and three received living donors LT. All patients were diagnosed with COACH syndrome by genetic testing. LT was performed in these patients at 3, 7, 9, and 14 years old. The indication for LT was varices related to portal hypertension in all patients. One showed an intrapulmonary shunt. Blood tests revealed renal impairment due to nephronophthisis in three patients, and one developed renal insufficiency after LT. The liver function was maintained in all patients. A literature review revealed detailed information for three more patients. The indication for LT in these three cases was portal hypertension, such as bleeding from esophageal varices. One patient had chronic renal failure on hemodialysis at LT and underwent combined liver and kidney transplantation. Of these three previous patients, one died from hepatic failure due to de novo HCV infection 3 years after LT. CONCLUSIONS: LT should be considered an effective treatment for COACH syndrome in patients with severe portal hypertension. However, a detailed follow-up of the renal function is necessary.

Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.

Significance of a multidisciplinary approach to congenital extrahepatic portosystemic shunt: A changing paradigm for the treatment.

AIM: To review the current institutional practice to treat patients with congenital extrahepatic portosystemic shunt (CEPS) and to determine the optimal strategy. METHODS: We retrospectively reviewed the records of 55 patients diagnosed with CEPS at our center between December 2008 and March 2022. RESULTS: Among these 55 patients, 44 (80.0%) received treatment for CEPS at a median age of 4.7 years. The most common indication for treatment was cardiopulmonary complications (45.5%). Therapeutic intervention included shunt closure by endovascular techniques (50.0%) or surgery (40.9%), and liver transplantation (9.1%). A total of 11 were classified as short shunt types, and surgical ligation was performed in all to preserve the major vascular system and prevent complications (p < 0.001). Children who received a surgical ligation were more likely to develop complications after shunt closure (p = 0.02). Among seven patients with portopulmonary hypertension (POPH), one patient, who received a shunt ligation at <1 year-of-age, was only able to completely discontinue medication. Most other CEPS-related complications were completely resolved. Post-treatment complications, including thrombosis and symptoms of portal hypertension, were seen in 16 patients. After shunt closure, one patient was scheduled to undergo liver transplantation for progressive POPH and large residual hepatocellular adenoma. During follow-up, one patient without any treatment for CEPS developed POPH 16 years from the diagnosis. CONCLUSION: Earlier therapeutic interventions should be strongly considered for patients with POPH related to CEPS. However, in view of the invasiveness and treatment complications, special attention should be paid to the management of patients with short shunt types.

Rare sequence variants associated with the risk of non-syndromic biliary atresia.

AIM: The etiology of non-syndromic biliary atresia (BA) remains largely unknown. In this study, we performed genome-wide screening of genes associated with the risk of non-syndromic BA. METHODS: We analyzed exome data of 15 Japanese patients with non-syndromic BA and 509 control individuals using an optimal sequence kernel association test (SKAT-O), a gene-based association study optimized for small-number subjects. Furthermore, we examined the frequencies of known BA-related single-nucleotide polymorphisms in the BA and control groups. RESULTS: SKAT-O showed that rare damaging variants of MFHAS1, a ubiquitously expressed gene encoding a Toll-like receptor-associated protein, were more common in the BA group than in the control group (Bonferroni corrected p-value = 0.0097). Specifically, p.Val106Gly and p.Arg556Cys significantly accumulated in the patient group. These variants resided within functionally important domains. SKAT-O excluded the presence of other genes significantly associated with the disease risk. Of 60 known BA-associated single-nucleotide polymorphisms, only eight were identified in the BA group. In particular, p.Ile3421Met of MYO15A and p.Ala421Thr of THOC2 were more common in the BA group than in the control group. However, the significance of these two variants is questionable, because MYO15A has been linked to deafness, but not to BA, and the p.Ala421Thr of THOC2 represents a relatively common single-nucleotide polymorphism in Asia. CONCLUSIONS: The results of this study indicate that rare damaging variants in MFHAS1 may constitute a risk factor for non-syndromic BA, whereas the contribution of other monogenic variants to the disease predisposition is limited.

Successful pediatric liver transplantation case with a positive SARS-CoV-2 test at the time of transplant.

AIM: We report a successful liver transplantation (LT) in a child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE PRESENTATION: A 3-year-old female patient with decompensated cirrhosis due to Alagille syndrome underwent a split LT with a left lateral segment graft. She had a history of SARS-CoV-2 infection 4 months before LT. She was exposed to SARS-CoV-2 after the decision for organ acceptance. We repeatedly confirmed the negative SARS-CoV-2 test by polymerase chain reaction (PCR) before LT. Liver transplantation was carried out in the negative pressure operational theater with full airborne, droplet, and contact precautions as the patient was considered to be within the incubation period of SARS-CoV-2. The SARS-CoV-2 PCR test became positive in the nasopharyngeal swab specimen at the operation. Remdesivir, the antiviral treatment, was held off due to potential hepatotoxicity and no exacerbation of COVID-19. She received tacrolimus and low-dose steroids per protocol. She remained SARS-CoV-2 positive on postoperative days (PODs) 1, 2, and 5. The presence of antibodies for SARS-CoV-2 at LT was confirmed later. On POD 53, she was discharged without any symptomatic infection. CONCLUSION: This case demonstrated that a positive SARS-CoV-2 result was not an absolute contraindication for a life-saving LT. Liver transplantation could be safely performed in a pediatric patient with asymptomatic COVID-19 and S-immunoglobulin G antibodies for SARS-CoV-2.

Portal vein pressure and flow modulation in pediatric liver transplantation.

Liver transplantation (LT) has been indicated for smaller and more clinically severe patients in recent years. Small biliary atresia (BA) patients often show portal hypoplasia and sclerotic portal vein (PV), which may make PV reconstruction more difficult during the operation. Among PV complications, intraoperative PV thrombosis can be considered a disaster, and it is important to prevent this catastrophic event by the precise assessment of the PV structure and PVF using radiological imaging before and during LT. However, there are no objective parameters to indicate whether sufficient PVF can be obtained. PV pressure (PVP) and PV flow (PVF) have mainly been studied in adult living donor LT, for the purpose of preventing small-for-size syndrome, and PVP has been considered an objective parameter of graft inflow modulation (GIM). In the setting of pediatric LT, GIM is mainly performed to prevent hypoperfusion, and it must be performed before graft implantation. GIM to maximize the PVF of pediatric patients with potentially low PVF in LT consists of the interruption of collateral vessels, the assessment of the usability of the native PV, and technical modifications in PV reconstruction. Reliable objective parameters that represent sufficient PVF before graft implantation are desired. Our recent study proposed that a PVP of ≥25 mmHg before graft implantation can be considered an objective parameter to obtain sufficient PVF (cutoff value: 50 mL/min/100 g of graft weight). Further investigation is needed to determine the best strategy for successful PV reconstruction in pediatric LT.

Optimal liver transplant procedure in progressive familial intrahepatic cholestasis type 1 treated with biliary diversion or intestinal transplantation: Lessons learned from three cases treated with different approaches.

BACKGROUND: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an autosomal recessive cholestatic liver disorder caused by ATP8B1 gene mutations. Although liver transplantation (LT) is indicated for progressive liver disease, postoperative complications, including severe diarrhea and graft steatohepatitis leading to graft loss, have been reported. CASES: The first patient had jaundice, pruritus, diarrhea, and growth retardation (weight z-score: -2.5; height z-score: -3.7). She underwent LT with total internal biliary diversion (TIBD) to the colon at 2 years of age. Graft biopsy at the 7-year follow-up examination revealed microvesicular steatosis (60%). Her diarrhea improved, and her growth failure was recovering (weight z-score: -1.0; height z-score: -1.7). The second patient underwent sequential intestine-liver transplantation at 8 years of age due to end-stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21 months of age. She developed severe pancreatitis induced by steroid-bolus therapy for rejection after transplantation. She died 1.7 years after intestinal transplantation due to an uncontrollable pancreatic abscess and acute respiratory distress syndrome. The third patient underwent PEBD at 15 months of age and received LT with TEBD at 15 years of age due to ESLD with hepatic encephalopathy. Throughout the perioperative period, she showed no abdominal symptoms, including diarrhea and pancreatitis. Graft biopsy at the 2-year follow-up examination revealed macrovesicular steatosis (60%) with inflammation. CONCLUSIONS: The patients showed different outcomes. Effective therapeutic options to mitigate post-LT complications in patients with PFIC1 must be considered individually.

Gallstone ileus at 17 years after living donor liver transplantation: A case report.

BACKGROUND: Gallstone ileus (GI) occurs in <0.1% of all cases of mechanical bowel obstruction. There have been a few reports of GI occurring after Kasai procedures or Roux-en-Y anastomosis for bariatric surgery. We herein report a case of GI that occurred over 17 years after liver transplantation (LT). CASE REPORT: A 33-year-old woman who had undergone living donor LT for biliary atresia at 16 years old and had been regularly followed on an outpatient basis in our hospital presented with the sudden onset of increased abdominal distension, pain, and nausea. Enhanced abdominal computed tomography showed dilatation of the intrahepatic bile duct and the whole intestinal tract of the Roux limb as well as ischemic changes near the jejuno-jejunal anastomosis. On laparotomy, a movable and hard foreign body was palpated in the intestinal tract close to the jejuno-jejunal anastomosis site. Enterotomy was performed, and a 4-cm gallstone was removed. The patient had a good postoperative course and was discharged on postoperative day 12. CONCLUSIONS: Although GI after LT is a rare complication, it may need to be differentiated as a cause of ileus. An accurate differential diagnosis and early reliable intervention for stone removal will help prevent serious bowel complication, which may lead to graft dysfunction.

Rescue venovenous extracorporeal membrane oxygenation for the deterioration of acute respiratory distress syndrome in pediatric liver transplantation.

BACKGROUND: Twenty percent of pediatric patients with BA develop ACLF with increased mortality while awaiting LT. Respiratory complications are common in pediatric ACLF and are associated with increased morbidity and mortality. ARDS is the most severe manifestation of acute respiratory failure with considerable risk of mortality. METHODS: A 5-month-old girl with post-Kasai BA preoperatively experienced ARDS from RSV infection while awaiting LT. She developed decompensated liver failure with shock, acute kidney injury, coagulopathy, and pulmonary hemorrhage after several episodes of sepsis over the course of 1 month in the PICU. At this stage, RSV was not detected in the patient's tracheal aspirate by real-time polymerase chain reaction. She underwent living donor LT to manage her pre-existing critical state. Following reperfusion during LT, her pre-existing ARDS rapidly deteriorated, which was alleviated by intraoperative VV ECMO. RESULTS: Severe respiratory acidosis improved rapidly following ECMO, and LT was completed uneventfully. The patient was successfully weaned off ECMO on POD 3. CONCLUSIONS: This is the first pediatric case rescued by the intraoperative application of ECMO during LT. Our case and cumulative evidence suggest that VV ECMO can serve as rescue therapy for perioperative refractory respiratory failure in pediatric LT.

Hematological and biochemical characteristics and diagnostic imaging results in acute T cell-mediated rejection after pediatric liver transplantation.

BACKGROUND: Liver biopsy is the gold standard for diagnosing TCMR after LT. However, complications caused by liver biopsy may occur especially during the immediate post-transplantation period and other effective methods for predicting TCMR have not been established. Thus, we investigated whether hematological and biochemical characteristics and Doppler ultrasonography findings are associated with acute TCMR. METHODS: A multiple logistic regression analysis was performed to identify the prognostic factors of acute TCMR, defined as a RAI ≥4. Then, a ROC curve analysis was conducted to evaluate for diagnostic performance. The relationship between prognostic factors and each histological category of RAI was investigated. RESULTS: Eighty-nine liver biopsies were performed on 85 patients between January 2012 and December 2019. The RAI of 62 (69.7%) liver biopsies was ≥4. AEC (×104 /µl), direct bilirubin level (mg/dl), and MHVV (cm/s) were found to be associated with acute TCMR (OR: 4.96, 95% CI: 1.44-17.0, p = .011; OR: 1.41, 95% CI: 1.04-1.91, p = .025; OR: 1.05, 95% CI: 1.02-1.08, p < .001, respectively). The area under the ROC curves for predicting acute TCMR was 0.86 (95% CI: 0.78-0.94). There was a correlation between AEC, direct bilirubin level, and MHVV as well as the severity of RAI. CONCLUSIONS: AEC, direct bilirubin level, and MHVV were the independent risk factors for acute TCMR. This study could provide information regarding the identification of patients requiring liver biopsy.

Surgical technique and the long-term outcomes of pediatric living donor domino liver transplantation from patients with maple syrup urine disease.

BACKGROUND: The native liver of patients with maple syrup urine disease (MSUD) (1st recipients) can be used as a graft for non-MSUD patients with end-stage liver disease (2nd recipients). This study aimed to demonstrate the optimal operational procedures and the long-term outcomes of 2nd recipients. METHODS: Six 2nd recipients of living donor domino liver transplantation (LD-DLT) (age: 42.5 [22-169] months at DLT) received a native liver as a graft from an MSUD patient at our hospital between June 2014 and April 2020. We reviewed the operational procedures and outcomes of 2nd recipients after LD-DLT. RESULTS: The 2nd recipients' original diseases included biliary atresia, congenital hepatic fibrosis, congenital protein C deficiency, familial hypercholesterolemia, hepatoblastoma, and mitochondrial hepatopathy. Five of the six recipients had a whole liver and one had a right lobe graft. The site at which the vessels of the MSUD liver were dissected prioritized the safety of the 1st recipient. At the end of follow-up, all recipients were doing well without surgical complications. The mean serum amino acid values of the 2nd recipients did not exceed the upper limit of the reference values during the long-term observation period. All patients showed normal growth while maintaining the same z-score of height and weight after LD-DLT as the preoperative level. CONCLUSION: The liver of patients with MSUD can be used safely without concern regarding long-term complications or de novo MSUD development. LD-DLT using the MSUD liver can expand the donor pool as an alternative graft in pediatric LT.

Preemptive liver transplant in two patients with primary hyperoxaluria type 1: Clinical significance of nephrolithiasis and nephrocalcinosis.

BACKGROUND: Although nephrolithiasis (NL) and nephrocalcinosis (NC) are very common features of primary hyperoxaluria type 1 (PH1), the long-term prognosis of NL and NC after preemptive liver transplantation (PLT) has not been elucidated. MATERIAL AND METHODS: We describe the cases of two chronic kidney disease (CKD) stage three patients with different clinical courses after PLT for PH1. RESULTS: The first patient underwent PLT at 7 years of age with an estimated glomerular filtration rate (eGFR) of 47.8 ml/min/1.73 m2 . Two years later, she experienced several episodes of obstructive pyelonephritis due to urolithiasis, and developed septic shock in one of these episodes. At the same time as these episodes, preexisting NL and NC progressively improved, with disappearance on X-ray disappeared at 8 years after transplantation. Her renal function has been maintained with an eGFR of 58.7 ml/min/1.73 m2 . The second patient received PLT at 10 years of age with an eGFR of 58.9 ml/min/1.73 m2 . Her renal function has been maintained with an eGFR of 65.9 ml/min/1.73 m2 . She had repeated urolithiasis which started to appear at 3 years after LT. The radiological findings still show bilateral NL and NC, but the stones in the renal pelvis have shown mild improvement. CONCLUSIONS: Regardless of the regression in NC seen on X-ray, long-term maintenance of the renal function in patients with PH1 with CKD stage 3 can be achieved with PLT. In patients with NL, there is a risk of serious complications due to posttransplant immunosuppressive therapy when obstructive pyelonephritis occurs after LT.

Quantification of Maternal Microchimeric Cells in the Liver of Children With Biliary Atresia.

ABSTRACT: Biliary atresia (BA) is a rare disorder of unknown etiology. There is a debate as to whether maternal microchimerism plays a significant role in the development of BA or in graft tolerance after liver transplantation. Here, we performed quantitative-PCR-based assays for liver tissues of children with BA and other diseases. Maternal cells were detected in 4/13 and 1/3 of the BA and control groups, respectively. The estimated number of maternal cells ranged between 0 and 34.7 per 106 total cells. The frequency and severity of maternal microchimerism were similar between the BA and control groups, and between patients with and without acute rejection of maternal grafts. These results highlight the high frequency of maternal microchimerism in the liver. This study provides no evidence for roles of microchimerism in the etiology of BA or in graft tolerance. Thus, the biological consequences of maternal microchimerism need to be clarified in future studies.

Marginal parental donors for pediatric living donor liver transplantation.

PURPOSE OF REVIEW: Living donor liver transplantation (LT) has been increasingly recognized as an effective treatment modality with excellent patient survival. Indications for LT have evolved not only for cholestatic liver disease, but also metabolic liver diseases. Living donor selection, particularly for pediatric inherited disease, is essential to prevent morbidity, both in the donor and recipient. RECENT FINDINGS: Based on 30 years of experience in pediatric living donor LT in Japan, we could identify marginal parental living donors who have potential risks following LT, including heterozygous mothers with ornithine transcarbamylase deficiency, heterozygous protein C deficiency, heterozygous hypercholesterolemia, heterozygous protoporphyria, asymptomatic parental donors with paucity of intrahepatic bile duct, and human leukocyte antigen-homozygous parental donors. SUMMARY: Although these situations seem rare due to infrequency of the condition, careful living donor evaluation is required to optimize the outcomes for pediatric recipients. In the setting of an appropriate selection of a living donor, we should avoid any additional hazards, given that the procedure itself has risks for a healthy individual.

Humanized liver mouse model with transplanted human hepatocytes from patients with ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is a metabolic and genetic disease caused by dysfunction of the hepatocytic urea cycle. To develop new drugs or therapies for OTCD, it is ideal to use models that are more closely related to human metabolism and pathology. Primary human hepatocytes (HHs) isolated from two patients (a 6-month-old boy and a 5-year-old girl) and a healthy donor were transplanted into host mice (hemi-, hetero-OTCD mice, and control mice, respectively). HHs were isolated from these mice and used for serial transplantation into the next host mouse or for in vitro experiments. Histological, biochemical, and enzyme activity analyses were performed. Cultured HHs were treated with ammonium chloride or therapeutic drugs. Replacement rates exceeded 80% after serial transplantation in both OTCD mice. These highly humanized OTCD mice showed characteristics similar to OTCD patients that included increased blood ammonia levels and urine orotic acid levels enhanced by allopurinol. Hemi-OTCD mice showed defects in OTC expression and significantly low enzymatic activities, while hetero-OTCD mice showed residual OTC expression and activities. A reduction in ammonium metabolism was observed in cultured HHs from OTCD mice, and treatment with the therapeutic drug reduced the ammonia levels in the culture medium. In conclusion, we established in vivo OTC mouse models with hemi- and hetero-patient HHs. HHs isolated from the mice were useful as an in vitro model of OTCD. These OTC models could be a source of valuable patient-derived hepatocytes that would enable large scale and reproducible experiments using the same donor.

Safety of LAVs administered after pediatric LT.

Recent guidelines suggest that LAVs may be given to LT recipients meeting certain criteria. However, information is still limited. We sought to evaluate the safety of LAVs, including measles, mumps, rubella, and varicella to LT recipients following our clinically based immunization protocol for LT recipients. We conducted a case-series analysis on safety of LAVs for measles, rubella, varicella, and mumps given to LT recipients at our institution from July 2010 to July 2019. Patients who underwent LT at age <20 years who visited our immunization clinic were included. LT recipients were vaccinated if 2 years had lapsed from LT, had no signs of rejection within 6 months, and were on minimal immunosuppressants. Patient demographics, underlying diseases, type and number of vaccines administered, date of vaccination, and adverse events occurring within 4 weeks after vaccination were extracted from their medical records. During the study period, LAVs were administered 422 times to 209 patients who met criteria and included 225 doses of MR combination vaccine, 224 doses of varicella vaccine, and 215 doses of mumps vaccine. Underlying diseases included cholestatic liver diseases (n = 125), followed by metabolic diseases (n = 33) and acute liver failure (n = 19). Nine non-critical adverse events (2.1%) possibly associated with LAVs were reported, but there were no serious adverse events, including hospitalizations or deaths. In conclusion, LAVs administered to LT recipients were safe without any serious adverse events following our relatively simple institutional protocol.

Impact of sarcopenia in infants with liver transplantation for biliary atresia.

While sarcopenia is an important predictor of LT outcomes in adults, few studies have examined the association of sarcopenia with LT outcomes in pediatric patients. We investigated the clinical influence of sarcopenia on the post-transplant outcomes in infants with BA. To define sarcopenia in infants, the cross-sectional area of the tPMA in 93 healthy control infants was measured by computed tomography. Sarcopenia was defined as a tPMA lower than two standard deviations below the mean of healthy control infants. Eighty-nine infants with BA with a median age at LT of 7.6 months old were enrolled. The clinical characteristics and outcomes of LT were verified in the sarcopenia group (n = 21) and non-sarcopenia group (n = 68). The sarcopenia group had a significantly longer operation time and greater blood loss during LT than the non-sarcopenia group (P = .03 and 0.02). The incidence of portal vein stenosis and post-operative bloodstream infection was also significantly higher in the sarcopenia group than in the non-sarcopenia group (23.8% vs 4.4%, P = .02 and 28.6% vs 10.3%, P = .04, respectively). The total length of hospital stay did not differ significantly. The 1-year patient and graft survival rates tended to be lower in the sarcopenia group than in the non-sarcopenia group (90.5% vs 98.5%, P = .07 and 85.7% vs 97.1%, P = .05, respectively). Sarcopenia in infants with BA may be associated with the patient survival and serve as an effective marker for post-operative outcomes of LT.

Segmental Atrophy of Explanted Livers in Biliary Atresia: Pathological Data From 63 Cases of Failed Portoenterostomy.

OBJECTIVES: Atrophy of the left lateral segment (LLS) is often encountered in liver transplantation (LT) for biliary atresia (BA). To clarify the meaning of the heterogeneous atrophy, we compared the pathological characteristics of the LLS with the right posterior segment (RPS) of BA livers obtained during LT. METHODS: Among the 116 patients with BA who underwent LT at our hospital between 2014 and 2018, 63 patients with persistent cholestasis after the Kasai portoenterostomy (KP) were selected. Three pathologists evaluated tissues from the LLS and RPS for 5 pathological parameters. Positive areas in whole-slide image observed as portal inflammation, fibrosis, cholestasis, and ductular reaction, were analyzed with automated image quantitation. Moreover, we examined the relationship between the pathological score and the Pediatric End-stage Liver Disease (PELD) score. RESULTS: The median age at LT was 7 months (range 4-26 months). Inflammation and fibrosis were significantly greater in the LLS than in the RPS (P < 0.001, for both); however, there were no differences in cholestasis, ductular reaction, and hepatocellular damage (P = 0.3, 0.3, and 0.82). The same results were obtained in automated image quantitation. Moreover, the sums of the 5 pathological scores in the LLS showed a significant positive correlation with the PELD score (P = 0.016, rs = 0.3). CONCLUSIONS: More severe inflammation and fibrosis without cholestasis were observed in the LLS. The segmental atrophy may not be associated with poor bile drainage, but with etiopathogenesis of BA. Moreover, the proper site for biopsy during KP could be the LLS.

Efficacy of intraoperative cine-portogram for complicated portal vein reconstruction in pediatric living donor liver transplantation.

Sufficient PV flow is necessary to achieve successful PV reconstruction in pediatric LDLT. IOCP can be used to assess the severity of PV stenosis and to identify potential portosystemic collateral pathways. The present study reviewed the utility of IOCP and the outcomes of patients who underwent assessment with an IOCP. Consecutive primary LDLTs were performed in 488 pediatric recipients between November 2005 and October 2019. IOCP was used in patients who were unable to achieve sufficient PV flow after the ligation of collaterals. In total, 11 patients underwent IOCP to assess potential portosystemic collateral pathways. The median age and body weight was 8 months (IQR, 6-11 months) and 6.6 kg (IQR, 5.7-8.9 kg), respectively. The reasons for using the IOCP were recurrent PV thrombus in seven patients and insufficient PV flow in four patients. IOCP revealed remaining collaterals in six patients and residual hypoplastic PV in eight patients. Two patients required additional interruption of the potential collaterals under IOCP, which were unable to be recognized as a dominant portosystemic collateral pathway on preoperative imaging. All eight patients with residual hypoplastic PV required vein graft interposition for the complete removal of the hypoplastic PV. All the patients are currently doing well with a median follow-up period of 4.9 years (IQR, 2.2-5.6 years). IOCP can be an effective tool for precisely detecting occult portosystemic collateral pathways and for assessing the patency of the PV anastomosis in pediatric LDLT.

Outcomes of liver transplantation for mitochondrial respiratory chain disorder in children.

AIM: Mitochondrial respiratory chain disorder (MRCD) can cause acute liver failure (ALF), which may necessitate liver transplantation (LT). However, MRCD is often difficult to diagnose before LT and the indications of LT are controversial due to the likelihood of progressive neurological disease. The present study further characterized the patient population and described the outcomes. METHODS: Thirteen patients who underwent LT for MRCD from November 2005 to May 2020 were enrolled in this study. RESULTS: Six of 13 MRCD patients were diagnosed with a mitochondrial inner membrane protein 17-related mitochondrial DNA depletion syndrome (MTDPS). Overall, nine survived with a median follow-up of 1.8 years (IQR, 1.3-5.1 years); four died within 2 years. In the long-term, seven survivors showed no progression of hypotonia after LT and attended a normal kindergarten or primary school. Neurological abnormalities were observed in two survivors, including vison loss related to Leber's hereditary optic neuropathy in one patient and psychomotor retardation related to Leigh syndrome in the other. Three non-survivors after LT were diagnosed with MTDPS and died of severe pulmonary hypertension, which had developed at 8, 9, and 18 months after LT (n=1 each). The remaining patient died of postoperative respiratory infection with respiratory syncytial virus. CONCLUSION: The long-term results support the performance of LT in patients with MRCD, although a genetic diagnosis is preferable for determining the accurate indications for LT in these patients. Furthermore, care should be taken to avoid complications due to mitochondrial dysfunction during the long-term follow-up.