Portosystemic Shunt Surgery for Extrahepatic Portal Venous Obstruction Beyond Endoscopic Variceal Eradication: Two Decades of Pediatric Surgical Experience.

Background: This exclusively surgical series on pediatric extrahepatic portal venous obstruction (EHPVO) defines surgical indications beyond endoscopic eradication of esophageal varices (EEEV), the selection of an appropriate surgical procedure, and the long-term post-surgical outcome. Methods: EHPVO management protocol at the reporting institute has been endotherapy until esophageal variceal eradication and surgery for select adverse sequelae manifesting after EEEV. Results: One hundred and thirty-nine EHPVO cases underwent surgery for the following indications in combination: i) massive splenomegaly with severe hypersplenism (n = 132, 95%); ii) growth retardation (GR, n = 95, 68%); iii) isolated gastric (IGV) and ectopic varices (n = 49, 35%); iv) Portal cavernoma cholangiopathy (PCC) (n = 07, 5%). A portosystemic shunt (PSS) was performed in 119 (86%) cases. Types of PSS performed were as follows: central end-to-side splenorenal shunt with splenectomy (n = 104); side-to-side splenorenal shunt (n = 4); mesocaval shunt (n = 1); inferior mesenteric vein (IMV) to left renal vein shunt (n = 2); IMV to inferior vena cava shunt (n = 3); H-graft interposition splenorenal shunt (n = 1); spleno-adrenal shunt (n = 3); makeshift shunt (n = 1). Esophagogastric devascularization (n = 20, 14%) was opted for only for non-shuntable anatomy. At a median follow-up (FU) of 41 (range: 6-228) months, PSS block was detected in 13 (11%) cases, with recurrent variceal bleeding in 4 cases. PCC-related cholestasis regressed in 5 of 7 cases. Issues of splenomegaly were resolved, and growth z-scores improved significantly. Conclusions: Endotherapy for secondary prophylaxis until EEEV has resulted in a shift in surgical indications for EHPVO. Beyond EEEV, surgery was indicated predominantly for non-variceal sequelae, namely massive splenomegaly with severe hypersplenism, GR, and PCC. Varices warranted surgery infrequently but more often from sites less amenable to endotherapy, i.e., IGV and ectopic varices. The selection of PSS was tailored to anatomy and surgical indications. On long-term FU post surgery, PSS block was detected in 13% of patients. PCC-related cholestasis regressed in 71%, and issues of splenomegaly resolved with significantly improved growth Z scores.

Shear Wave Elastography: A Reliable Secondary Parameter for Diagnosing Biliary Atresia in Infants With Neonatal Cholestasis.

Objective In this study, we aimed to optimize various grayscale, Doppler, and elastography parameters and evaluate their diagnostic performance in the preoperative diagnosis of biliary atresia (BA). Materials and methods A total of 158 infants aged <6 months with neonatal cholestasis (NC) were enrolled in the study and sonography was performed after four hours of fasting. For comparison of elastography, 31 exclusively age-matched controls, not suffering from liver disease, were included separately. Triangular cord and gallbladder (GB) parameters were considered as primary parameters, while right hepatic artery (RHA) caliber, RHA-to-right portal vein (RPV) ratio, hepatic subcapsular flow (HSF), and shear wave elastography (SWE) were considered as secondary parameters. Diagnosis of infants with BA was confirmed on histopathology. Data were presented as mean ±standard deviation (SD) and frequency. Differences between groups were compared using the Chi-square test and the unpaired student t-test. Receiver operating characteristic (ROC) curve analysis was done for individual ultrasound/Doppler/SWE parameters to calculate the optimal cutoff value. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for each parameter and their combinations. Results Of the primary parameters, GB contractility index (CI) and length showed the highest sensitivity and specificity respectively. A cutoff of 14 kPA was derived for SWE for the diagnosis of BA. Among secondary parameters, SWE had the best diagnostic performance, better than even the individual primary parameters. A combination of primary parameters with SWE in series showed the highest accuracy. Conclusion Among secondary parameters, elastography can prove to be highly useful. The highest accuracy in diagnosing BA can be obtained by combining primary parameters with SWE.

Gut and liver involvement in pediatric hematolymphoid malignancies.

Hematolymphoid malignancies are common neoplasms in childhood. The involvement of the gastrointestinal (GI) tract, liver, biliary system, pancreas, and peritoneum are closely interlinked and commonly encountered. In leukemias, lymphomas, and Langerhans cell histiocytosis (LCH), the manifestations result from infiltration, compression, overwhelmed immune system, and chemotherapy-induced drug toxicities. In acute leukemias, major manifestations are infiltrative hepatitis, drug induced gastritis, neutropenic typhlitis and chemotherapy related pancreatitis. Chronic leukemias are rare. Additional presentation in lymphomas is cholestasis due to infiltration or biliary obstruction by lymph nodal masses. Presence of ascites needs a thorough workup for the underlying pathophysiology that may modify the therapy and affect the outcome. Uncommon hematolymphoid malignancies are primary hepatic, hepatosplenic, and GI lymphomas which have strict definitions. In advanced diseases with extensive spread, it may be impossible to distinguish these diseases from the primary site of origin. LCH produces biliary strictures that mimic as sclerosing cholangitis. Liver infiltration is associated with poor liver recovery even after chemotherapy. The heterogeneity of gut and liver manifestations in hematolymphoid malignancies has a clinical impact on their management. Though chemotherapy is the mainstay of therapy in all hematolymphoid malignancies, debulking surgery and radiotherapy have an adjuvant role in specific clinical scenarios. Rare situations presenting as liver failure or end-stage liver disease require liver transplantation. At their initial presentation to a primary care physician, given the ambiguity in clinical manifestations and the prognostic difference with time-bound management, it is vital to recognize them early for optimal outcomes. Pooled data from robust registries across the world is required for better understanding of these complications.

Corrigendum to "Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for the Study of Liver (INASL), The Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN) and the Movement Disorders Society of India (MDSI)" [J Clin Exp Hepatol 9 (2019) 74-98].

[This corrects the article DOI: 10.1016/j.jceh.2018.08.009.].

Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Concurrent extrahepatic autoimmune disorders: unexplored dimension of autoimmune liver disease in children.

BACKGROUND AND AIM: No comprehensive and prospective data are available for concurrent extrahepatic autoimmune disorders (CEAIDs) in children with autoimmune liver disease (AILD). The aim of this study was to evaluate CEAIDs in AILD and their effect on AILD outcome. PATIENTS AND METHODS: Enrolled AILD and CEAIDs children were diagnosed on the basis of simplified and standard diagnostic criteria, respectively. The clinicopathological profile, treatment response, and outcome were compared between AILD with CEAIDs (group A) and AILD without CEAIDs (group B). RESULTS: In 62 AILD children, CEAIDs were found in 42% (n=26) [vitiligo (42%), celiac disease (CD) (15%), potential CD (15%), autoimmune hemolytic anemia (AIHA) (15%)]. CEAIDs were asymptomatic in 75%. Single CEAID was found in 81% (21/26) and multiple CEAID was found in 19% (5/26). Significantly less biochemical remission (46.1 vs. 74.2%, P=0.03), more treatment failure (23 vs. 3.2%, P=0.04), and higher mortality (15.3 vs. 3.2%, P=0.04) were encountered in group A compared with group B. On multivariate analysis (n=57), less biochemical remission in vitiligo (P=0.04); more treatment failure in AIHA (P=0.004) and vitiligo (P=0.04); and high mortality in AIHA (P=0.02) subgroups were reported. CD treatment has good impact on AILD outcome. All cases of diabetes mellitus in AILD were steroid-induced rather than because of autoimmunity (absence of antibody against tyrosine phosphatase and glutamic acid decarboxylase and elevated C-peptide). CONCLUSION: All AILD children should be screened for CEAIDs as the majority are asymptomatic. The AILD outcome was favorable in CD, but poor in vitiligo and AIHA. We suggest the incorporation of CEAIDs in a pediatric AILD scoring system.

Autoimmune acute liver failure and seronegative autoimmune liver disease in children: Are they different from classical disease?

OBJECTIVES: Presentation as autoimmune acute liver failure (AI-ALF) and seronegative autoimmune liver disease (SN-AILD) represents two uncommon variants of AILD. We compared the clinical profile and outcome of AI-ALF with autoimmune-non-acute liver failure (AI-non-ALF) and also SN-AILD with seropositive autoimmune liver disease (SP-AILD). MATERIALS AND METHODS: Children managed as AI-ALF and AI-non-ALF including SN-AILD and SP-AILD were enrolled and compared. AI-non-ALF was diagnosed by simplified diagnostic criteria and AI-ALF by Pediatric Acute Liver Failure Study Group criteria with positive autoantibody, exclusion of other etiologies, elevated immunoglobulin G and histology when available. RESULTS: Seventy children [AI-ALF=15 and AI-non-ALF=55 (SN-AILD=11, SP-AILD=44)] were evaluated. Age at presentation [7 (1.2-16) vs. 9 (2-17) years] percentage of female patients (67 vs. 62%), and AILD type (type II, 53 vs. 31%) were similar in AI-ALF and AI-non-ALF patients], respectively. 8/15 AI-ALF cases were treated with steroids (improved-4, liver transplant-1, and death-3) and 7/15 died before initiation of therapy. Hepatic encephalopathy (100 vs. 16.3%; P<0.001), massive hepatic necrosis (60 vs. 0%; P<0.001), and higher pediatric end-stage liver disease [n=53, 29.9 (13.1-56.9) vs. 9.8 (-10-28.7) P<0.001], model for end-stage liver disease [n=17, 38.5 (24-46) vs. 18 (6-24); P=0.005], and Child-Turcotte-Pugh [n=70, 13 (8-13) vs. 9 (5-13); P<0.001] scores were features of AI-ALF. Poorer response to immunosuppression (4/8 vs. 48/55; P=0.02) and higher mortality (11/15 vs. 4/55; P=0.0001) were seen in AI-ALF than in AI-non-ALF patients. Clinicolaboratory profile, therapeutic response, and outcome were similar in SN-AILD and SP-AILD. CONCLUSION: AI-ALF is characterized by poorer liver function, lower response to immunosuppression, and higher mortality compared with SP or SN AI-non-ALF, which are similar.

Varied Presentations of Acute Glomerulonephritis in Children: Single centre experience from a developing country.

OBJECTIVES: The objective of this prospective study, carried out at Manipal Teaching Hospital, Pokhara, was to document the various clinical presentations of children with acute glomerulonephritis and compare them with the available biological parameters in Western Nepal. METHODS: Clinical and laboratory parameters of children with oedema and microscopic/macroscopic haematuria. RESULTS: For seven years (2000-2007), 92 cases of children were clinically diagnosed with acute glomerulonephritis (AGN). Other clinical and laboratory anaylses were also eventful. CONCLUSION: The present study highlights the varied presentations of AGN, atypical presentations or complications of glomerulonephritis being more common than the classical presentation in the Western Region of Nepal.