Childhood Cirrhosis Research Articles

Adverse Childhood Experiences, Household Dysfunction and Cirrhosis

Adverse Childhood Experiences, Household Dysfunction and Cirrhosis

Evaluation of QT prolongation in children with cirrhosis and its association with the severity of liver diseases

Summary: Introduction: Prolongation of the QT interval in an electrocardiogram (ECG) is seen in more than 60% of adults with advanced cirrhosis. According to careful research, people with cirrhosis who have their QT intervals prolonged had worse survival rates, more severe disease symptoms, and faster development of their condition. Considering the importance of predicting complications of liver cirrhosis in children and the limited number of studies related to the relationship between prolonged QT and the severity of liver disease in children, in this study, prolonged QT in children with liver cirrhosis and its relationship with the severity of liver disease was investigated. Methods: In the present study, children under 18 years of age with liver cirrhosis were evaluated in the list of liver transplants referred to Abu Ali Sina Organ Transplantation Hospital in Shiraz between 2019 and 2021. QT was calculated based on two pediatric cardiologists‘ 12-lead ECG from liver transplant surgery. Results: In this study, 130 patients with liver cirrhosis with an average age of 7.05±5.34 years were evaluated. The average length of the QT segment was reported as 397±31milliseconds. Only 4 (3%) had a long QT segment in all the studied patients. The comparison of the Meld/ Peld criterion and Child criterion in the two groups of regular QT and prolonged QT showed that the mean of both criteria was signifi cantly longer in the standard QT group (P = 0.018, P = 0.038). Also, prolonged QT showed a signifi cant relationship with the cause of liver cirrhosis (P = 0.003). Conclusion: Our study is one of the fi rst to examine the relationship between QT and severity of cirrhosis in children. Based on the results of this study, prolonged QT is associated with severity of liver disease. Key words: liver – cirrhosis – children – long QT – fi brosis

Indian childhood cirrhosis: a retrospective study –redefining the older myths!

AimsThis retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management.MethodsThis study was done on liver archival...

HEPATOPULMONARY SYNDROME IN PEDIATRIC PATIENTS WITH PORTAL HYPERTENSION - AN INTEGRATIVE REVIEW.

Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVD) in the setting of advanced liver disease or portal hypertension, impacting the patient's quality of life and survival. There are still many gaps in the literature on this topic, especially in pediatrics, with practices frequently based on extrapolation of data obtained from adults. Provide a synthesis of the current knowledge about HPS in children. The research was carried out through narrative review. The databases used for the search include Medline, Embase, Elsevier, Lilacs and Scielo. The keywords used were "hepatopulmonary syndrome" AND child, children, infant, preschool, pediatric. In cirrhotic children, the prevalence of HPS can reach up to 42.5%, and it is even more common in those whose underlying condition is biliary atresia, reaching up to 63%. Screening with pulse oximetry (O2 saturation <96%), unlike in adults, has low sensitivity in the pediatric age group. Management involves supportive care with oxygen therapy; liver transplantation is the only definitive treatment to reverse the condition and HPS is considered an exceptional criterion for waitlist. The waitlist mortality is similar among children listed by HPS as a special criterion when compared to those listed for other reasons. The reported rates of complete resolution of hypo-xemia after liver transplantation are close to 100% in children. The post-liver transplantation survival is similar or slightly lower in children with HPS when compared to those without HPS. Contrary to findings from adults, no differences were found in post- liver transplantation mortality between children of different hypoxemia ranges, although longer mechanical ventilation time and hospital stay were observed in children with PaO2 <50 mmHg. HPS is not an uncommon complication of cirrhosis in children and adolescents, particularly when biliary atresia is the underlying condition. There are still many gaps to be filled regarding the condition, and this article demonstrates that not all data obtained in studies with adults reflects the disease's behavior in pediatrics, especially concerning prognosis.

Можливості еластографії зсувної хвилі в діагностиці фіброзу печінки та моніторингу автоімунних захворювань печінки в дітей

Autoimmune liver disease (ALD) in children, when not diagnosed and treated timely, are characterised by a progressive course leading to liver cirrhosis. Monitoring the progression of the disease is crucial for evaluating the effectiveness of treatment in ALD patients. We believe that the use of ultrasound elastography is not only valuable for diagnosing liver fibrosis but also for monitoring the course of ALD in children, representing a promising research method. Purpose - to assess the feasibility of using shear wave elastography for diagnosing liver fibrosis and monitoring the course of ALD in children. Materials and methods. In 108 children with ALD aged 3-18 years, examined at the Department of Pediatric Hepatology of the SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O. Lukyanova of the National Academy of Medical Sciences of Ukraine», from 2019 to 2023, ultrasound shear wave elastography (2D-SWE) parameters were evaluated before treatment (baseline) and at 6, 12, 24, and 36 months of therapy, depending on the stage of liver fibrosis determined by histological method using the Metavir scoring system (F0-F4) in all children. Statistical analysis was performed using GraphPad Prism 9 version 10.0.0. Results. The mean age of the children was 11 years (range 8-13.8 years), with 91% (n=98) having liver fibrosis stage ≥F2 according to Metavir. There was a significant correlation between complete biochemical remission and median 2D-SWE at 12, 24, and 36 months of treatment (p=0.0002; p=0.002; p=0.0004, respectively). The area under the ROC curve (AUC) for diagnosing liver fibrosis stage ≥F3 and F4 at 0, 6, 12, 24 and 36 months of treatment was 0.81; 0.78; 0.67; 0.81; 0.75 and 0.80; 0.91; 0.84; 0.89; 0.92, respectively. The optimal cutoff value for median 2D-SWE was 10.1 kPa; 8.9 kPa; 9.1 kPa; 8.9 kPa; 7.0 kPa and 14.0 kPa; 10.5 kPa; 10.2 kPa; 9.7 kPa; 8.1 kPa, respectively. Conclusions. Shear wave elastography is an effective method for diagnosing fibrosis ≥F3 and cirrhosis in children with ALD. Reduction in 2D-SWE values in children with ALD during treatment is a predictor of its effectiveness. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

The burden of cirrhosis and other chronic liver diseases due to hepatitis B in children and adolescents: results from global burden of disease study 2019.

The global burden of cirrhosis and other chronic liver diseases due to hepatitis B (collectively referred to as hepatitis B-associated cirrhosis in this paper) in children and adolescents must be understood and investigated. Data were extracted from the GBD database, and calculations were performed at global, regional, and national level. We calculate the incidence, prevalence, and disability-adjusted life years (DALYs) and annual average percentage changes (AAPCs). Globally, the prevalent cases of children and adolescents with hepatitis B-associated cirrhosis decreased from 125,053.98 × 10^3 in 1990 to 46,400.33 × 10^3 in 2019. Compared with 1990, the incidence rate of cirrhosis increased in low (95.51%) and low-middle SDI areas (26.47%), whereas it decreased in other SDI areas. The AAPC of incidence has increased in low-middle SDI areas (AAPC 0.12 [95% CI: 0.04-0.20]). At the regional level, the East Asia region has experienced the largest reduction. Conversely, Western Sub-Saharan Africa was the most serious region. Notably, South Asia was the only region where the AAPC of cirrhosis incidence (AAPC 0.77 [95% CI, 0.68-0.86]) increased. Globally, the overall burden of hepatitis B-associated cirrhosis in children and adolescents has declined significantly, but the number of cirrhosis incidence cases in low-middle and low-SDI areas has increased. The incidence in South Asia is rising, and the burden on Africa remains serious. Prevention and treatment of hepatitis B-associated cirrhosis in children and adolescents should not be ignored.

Galectin-3 in biliary atresia and other pediatric cholestatic liver diseases.

Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA. Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing. Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45-30.46] vs. 11.30 [8.74-16.83] ng/mL, p=0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3+ M2 macrophages in late BA in comparison to late other CLD (162 [157-233] vs. 49 [33-59] cells/mm2, p=0.03). The number of Galectin-3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation. Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.

Pediatric Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is characterized by an acute hepatic insult happening in a patient with underlying cirrhosis with compromised hepatic reserve leading to development of systemic inflammation, sepsis, and organ failure resulting in poor outcome in majority. While Asia Pacific Association for Study of Liver Diseases (APASL) emphasizes on early diagnosis before development of organ failure, European Association for Study of Liver Diseases (EASL) mandates the presence of organ failures to define ACLF. There is a lack of consensus definition of pediatric ACLF although recent APASL guidelines have tried to address the issue. While Wilson disease (WD) and autoimmune hepatitis (AIH) are the most common cause of underlying cirrhosis in children, acute viral hepatitis and flares of WD and AIH are the commonest acute precipitating events. Poor outcomes [death and liver transplantation (LT)] ranging from 19 to 59% have been reported. Prognosis in pediatric ACLF is usually better than that in adults due to greater proportion of treatable etiologies, lesser organ failures, comorbidities and better hepatic reserves. APASL ACLF Research Consortium (AARC) score more than or equal to 11 is predictive of poor 28-90 d mortality. Treatment of pediatric ACLF relies mainly on prompt diagnosis and medical management of a potentially treatable etiology of underlying cirrhosis. Bridging therapies, especially high volume plasma exchange can be initiated early as a bridge to LT or native liver recovery. Those with no improvement in 4-7 d should undergo LT before development of sepsis or multi-organ failure.

TOP-094 - Global, regional, and national burdens of cirrhosis in children and adolescents aged under 19 years from 1990 to 2019: a systematic analysis based on the global burden of disease study 2019

TOP-094 - Global, regional, and national burdens of cirrhosis in children and adolescents aged under 19 years from 1990 to 2019: a systematic analysis based on the global burden of disease study 2019

Disseminated langerhans cell histiocytosis presenting as decompensated childhood cirrhosis

Childhood cirrhosis is a rare disease of multifactorial etiopathogenesis. One of the rare underlying causes is Langerhans cell histiocytosis (LCH). The multifocal multisystemic variant of LCH can rarely involve the hepatobiliary system. Indirect and direct forms of hepatobiliary involvement are known. Early diagnosis of underlying liver involvement in cases of LCH is crucial to prevent decompensation and ameliorate prognosis post-liver transplantation. This is a case of an 18-month-old male child who developed cutaneous lesions in the early infancy. He was brought to clinical attention due to progressively increasing abdominal girth. His laboratory, clinical and radiological examination suggested multisystem pathology, subsequently confirmed on biopsy as LCH with predominant involvement of hepatobiliary, pulmonary, and integumentary systems. Unfortunately, he succumbed within a week of diagnosis.

Global, regional, and national burdens of cirrhosis in children and adolescents aged under 19 years from 1990 to 2019

Background & aimsCirrhosis was the leading cause of morbidity and mortality in adults, but data on the burden and trends were sparse in children and adolescents. We aimed to assess the trends in 204 countries and territories over the past 30 years in children and adolescents aged 0–19 years.MethodsData on cirrhosis was collected by the Global Burden of Disease (GBD) 2019 database from 1990 to 2019. We reported on the number, rates, and average annual percentage changes (AAPCs) of incidence and disability-adjusted life-years (DALYs) of cirrhosis at global, regional, and national level.ResultsGlobally, the incident numbers of cirrhosis in children and adolescents increased from 204,767 in 1990 to 241,364 in 2019, an increase of 17.9%, with an AAPC 0.13(0.10 to 0.16). Prevalence (AAPC = − 2.27[− 2.39 to − 2.15]), mortality (AAPC = − 1.68 [− 1.86 to − 1.5]), and DALYs rate (AAPC = − 1.72[− 1.88 to − 1.56]) of cirrhosis have decreased significantly. Cirrhosis incident rates varied between different ages. Cirrhosis caused by alcohol use (AAPC = 1[0.8 to 1.1]; incidence cases increased 48%), hepatitis C (AAPC = 0.4 [0.4 to 0.5]), NAFLD (AAPC = 0.5 [0.3 to 0.6]) have been increasing, while only hepatitis B (− 0.3[− 0.4 to − 0.2]) decreasing. Incidence cases of cirrhosis were increased in low (101.6%) and low-middle sociodemographic index (SDI 21.1%) areas, while decreasing in middle and above SDI areas. At the regional level, the largest increases count was observed in Sub-Saharan Africa.ConclusionsGlobal incidence rate of cirrhosis has been increasing, while the DALYs rate has been decreasing in children and adolescents. Morbidity of cirrhosis caused by hepatitis B declined, while hepatitis C, NAFLD, and alcohol use increased.

Impact of decompensated cirrhosis in children: A population-based study.

We describe the proportion of children with compensated cirrhosis who develop decompensation in Ontario, Canada over the past two decades. This is a retrospective population-based cohort study using routinely collected health care data from Ontario, Canada held at ICES during 1997-2017. Diagnosis of cirrhosis was made using validated ICES definition, and decompensation events were defined according to validated coding. Rates of decompensation, type of decompensation, and incidence of liver transplantation after decompensation were analyzed. Databases were linked at the individual level and analyzed at ICES-Queen's. A total of 2,755 children with compensated cirrhosis were included and 9% (253) developed decompensation over a median follow-up of 7 years. Children most likely to suffer decompensation were younger (median age 10 versus 4 years, p < 0.001) and female (45% versus 52%, p = 0.03). Ascites (137/253, 54%) was the most frequent complication. 199/2755 (7%) of children with cirrhosis received liver transplantation, of which 64% (128/199) occurred after a decompensation event. Overall, a total of 132 (4.7%) deaths occurred during the study period, with 55 deaths following a decompensating event. We present the first study to describe rates of decompensation, type, and rate of liver transplantation after decompensation in pediatric cirrhosis at the population level. To improve the care of children with liver disease, early detection of liver disease, early initiation of specific treatments as well as identification of children who are at risk of becoming decompensated are crucial.

Liver cirrhosis in children

Liver cirrhosis in children and adolescents is a consequence of a variety of chronic liver diseases, metabolic disorders, and genetic diseases. In infants, cirrhosis is most often due to biliary atresia and genetic-metabolic diseases, while in older children it usually occurs as a result of autoimmune hepatitis, Wilson’s disease, alpha-1 antitrypsin deficiency, and primary sclerosing cholangitis. Symptoms of cirrhosis in children and adolescents are not specific. In pediatric patients, the first sign of cirrhosis may more often be low weight gain, weakness, loss of appetite, low-grade fever, as well as more specific signs: transient jaundice, mild pruritus, epistaxis, heaviness in the right hypochondrium, changes in liver density on palpation, hyperbilirubinemia, hyperenzymemia, etc. Complications of pediatric cirrhosis are similar to those observed in adult patients and include gastrointestinal bleeding caused by esophageal varices, ascites, and spontaneous bacterial peritonitis. In pediatric practice, special attention should be paid to nutritional correction in liver cirrhosis since children have higher requirements for protein and micronutrients for growth and development. Treatment of cirrhosis-induced portal hypertension in children and adolescents is mainly based on methods developed for adults. The article deals with diagnostic and differential diagnostic aspects of the terminal stage of liver disease in children. The therapeutic management of patients with cirrhosis of the liver and acute renal failure is based on support of various organ functions. Hemodialysis/ plasmapheresis may serve in some patients as an interim therapy before liver transplantation. The indications for liver transplantation and problems arising after surgery are considered.

Liver cirrhosis

The liver cirrhosis (LC) is a severe disease, the 11th by the cause of death in the world, 50 % of patients die during 5 years. The most frequent etiological factors are alcoholic disease of the liver and chronic viral hepatitis. The following general pathological mechanisms are involved in LC pathogenesis: hepatocyte damage, endothelial dysfunction, oxidant stress, fibrosis activation, pathological regeneration, neoangiogenesis, architectonic impairment of the organ with the development of portal hypertension. Genetic factors contribute to the progression of the liver pathology. Depending on the LC etiology, there are the features of pathogenesis, clinical picture, morphology, diagnostics, treatment and prognosis for alcoholic liver disease, chronic viral hepatitis, nonalcoholic fat liver disease, autoimmune hepatitis, primary biliary LC, hemochromatosis, Wilson-Konovalov disease, A1-antitripcin deficiency disease. Among rare causes of LC, there are noted Budd-Chiari syndrome, cardiac cirrhosis, Indian childhood cirrhosis.

Liver cirrhosis in children – the role of imaging in the diagnostic pathway

Liver cirrhosis in children is a rare disease with multifactorial causes that are distinct from those in adults. Underlying reasons include cholestatic, viral, autoimmune, hereditary, metabolic and cardiac disorders. Early detection of fibrosis is important as clinical stabilization or even reversal of fibrosis can be achieved in some disorders with adequate treatment. This article focuses on the longitudinal evaluation of children with chronic liver disease with noninvasive imaging tools, which play an important role in detecting cirrhosis, defining underlying causes, grading fibrosis and monitoring patients during follow-up. Ultrasound is the primary imaging modality and it is used in a multiparametric fashion. Magnetic resonance imaging and computed tomography are usually applied second line for refined tissue characterization, clarification of nodular lesions and full delineation of abdominal vessels, including portosystemic communications.

Early predictors of unfavourable outcome in progressive cholestasis of northwestern Quebec.

Progressive cholestasis of northwestern Quebec (PCNQ) is a rare and severe form of cirrhosis affecting children from Quebec's First Nations. First described by our group in 1981 and historically named North American Indian childhood cirrhosis, such a condition often requires liver transplantation during the pediatric age. This study aimed at suggesting a more culturally sensitive name for the disease and identifying early prognostic factors for an unfavourable outcome. We retrospectively collected data of all 14 consecutive patients diagnosed with PCNQ over the last 20 years and compared children listed for liver transplant before 18 years of age (LT, n = 7) to those with milder disease progression (no-LT, n = 7). Compared with the no-LT group, LT children developed serious complications with an unusually high incidence of gastrointestinal bleeding. Over the first 12 months from presentation, a greater increase of alanine aminotransferase plasma levels, decrease of total bilirubin, and increase of alanine aminotransferase-to-total bilirubin ratio was observed in the LT group. Bone mineral density was lower in LT children independently of vitamin D levels. Patients with PCNQ showed poorer bone health than age-matched children with other cholestatic disorders. In the name of cultural sensitivity, PCNQ should be the preferred name for this condition. Variation of alanine aminotransferase and total bilirubin plasma levels over the first 12 months from presentation might be used for the early identification of children with PCNQ who are at higher risk of unfavourable outcomes. This might help optimize clinical management to populations that are underserved by health care services.

Global, Regional, And National Burdens of Cirrhosis in Children and Adolescents Aged Under 19 Years from 1990 to 2019: A Systematic Analysis Based on the Global Burden of Disease Study 2019

Global, Regional, And National Burdens of Cirrhosis in Children and Adolescents Aged Under 19 Years from 1990 to 2019: A Systematic Analysis Based on the Global Burden of Disease Study 2019

Неинвазивные маркеры фиброза и цирроза печени у детей с билиарной атрезией

Objective. To identify non-invasive laboratory and ultrasound markers of liver fibrosis and cirrhosis in children with biliary atresia. Patients and methods. This retrospective study enrolled 166 children who underwent the Kasai procedure for biliary atresia. Intraoperative liver biopsy followed by histological examination of the biopsy specimen was performed in all children. According to the results of morphological analysis, patients were divided into two groups: group I included 108 children with moderate fibrosis (F0–2), group II – 58 children with severe liver fibrosis/cirrhosis (F3–4). Prior to surgery, patients underwent a comprehensive examination, which included laboratory parameters (platelets, albumin, gamma-glutamyl transpeptidase, cholinesterase, cholesterol, alkaline phosphatase, total and direct bilirubin, alanine aminotransferase, aspartate aminotransferase, fibrinogen, international normalized ratio, thrombin time, prothrombin index, APRI and AAR indices), and Doppler ultrasound. Results. The correlation analysis revealed a statistically significant, direct, very strong correlation between the degree of fibrosis and patient age at the time of biopsy (ρ = 0.805; p &lt; 0.001), APRI index (ρ = 0.827; p = 0.001), and the hepatic artery diameter (ρ = 0.794, p = 0.042). The correlation between the degree of liver fibrosis and spleen length was statistically significant, direct, and of marked strength (ρ = 0.686; p = 0.010). There was a statistically significant, direct, notably strong correlation between the hepatic artery resistive index (RI) (ρ = 0.639; p = 0.05) and hepatic artery diameter-to-portal vein diameter ratio (HAD-to-PVD ratio) (ρ = 0.683, p = 0.047). The dependence of the probability of liver fibrosis/cirrhosis severity on the values of APRI index was assessed using ROC curves. The AUC value was 0.792 ± 0.056 (95% CI: 0.76–0.88, p = 0.009). The APRI value at the cut-off point was 1.52: with an APRI &gt;1.52 showing a high risk of severe liver fibrosis/cirrhosis, and with lower values, the risk of severe fibrosis/cirrhosis was considered low. The sensitivity and specificity of the model were 73.9 and 71.1%, respectively. Conclusion. The results of the study indicate the significance of biochemical, ultrasound and Doppler parameters in the diagnosis of liver fibrosis/cirrhosis in children with biliary atresia. Key words: biliary atresia, liver fibrosis, liver cirrhosis, APRI index

Characterization of Androgen Receptor Complex Associated Protein (ARCAP) in hepatocellular carcinoma and liver.

Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly developing a general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile male hepatitis B virus transgenic mice have a greater occurrence of HCC than females. We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various expressions in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates the interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/). The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an Androgen Receptor Complex Associated Protein (ARCAP), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP is highly expressed in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP. We aim to search for different types and levels of steroid receptors expressed within human HCCs and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.

Chelation therapy in liver diseases of childhood: Current status and response.

Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson’s disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine. D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation. Trientine, an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects. The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD. Indian childhood cirrhosis is related to excessive copper ingestion, rarely seen in present era. D-Penicillamine is effective in the early part of this disease with reversal of clinical status. Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias. There are strict chelation protocols during bone marrow transplant. The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy. Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.