Childhood Cirrhosis Research Articles

Beyond the lungs: Alpha-1 antitrypsin's potential role in human gestation.

Alpha-1 antitrypsin (AAT) is an acute-phase protein with strong inhibitory activity towards proteolytic enzymes, mainly elastase but also trypsin, chymotrypsin and thrombin. The biological role of the protein and the effects of its deficiency have been subjects of scientific research for years, yet in many areas our knowledge remains incomplete. Alpha-1 antitrypsin deficiency (AATD), a defect in AAT synthesis and functionality, is one of the most frequently inherited genetic disorders among Caucasian populations. Its severe form is characterized by very low serum levels of AAT, and it most often affects the lungs (causing early-onset emphysema or chronic obstructive lung disease (COPD)) and/or liver (leading to jaundice and liver cirrhosis in children and adults). However, little is known about other possible clinical consequences of AAT deficiency. We discuss AAT's potential role in mechanisms regulating human fertility and gestation, with a particular emphasis on the clinical context and on indications for AATD diagnostic testing.

Prevalence and characteristics of hepatopulmonary syndrome in children with cirrhosis in southern Brazil.

Hepatopulmonary syndrome (HPS) is defined as a triad characterized by arterial deoxygenation, intrapulmonary vascular dilatations (IPVDs), and liver disorder. The aims of this study were to assess the prevalence of HPS in children with cirrhosis, the clinical characteristics of patients with HPS, and the tests used for the diagnosis of IPVD. This was a prospective, cross-sectional study of 40 children with cirrhosis (median age: 44 months). Investigations of HPS included arterial blood gas analysis, contrast-enhanced transthoracic echocardiography (CE-TTE), and perfusion lung scanning using technetium-99m-labeled macroaggregated albumin (Tc-MMA). Patients' clinical characteristics (age, etiology of cirrhosis, and severity of hepatopathy) were assessed. HPS was defined as liver disease; alveolar-arterial oxygen gradient of at least 15 mmHg and/or partial pressure of arterial oxygen less than 80 mmHg; and detection of IPVD by CE-TTE or Tc-MMA scanning. Statistical significance was indicated by a P value less than 0.05. The prevalence of HPS was 42.5% (17/40). Eight patients had moderate HPS (47%) and two patients had severe HPS (12%). In bivariate analysis, biliary atresia (P=0.033) and median age (10 months; P=0.005) were associated with HPS. In multivariate analysis, only age remained statistically significant (prevalence ratio=0.99; 95% confidence interval=0.98-0.99; P=0.010). Sixteen patients with HPS had IPVD detected by CE-TTE (94.1%) and six patients had IPVD detected by Tc-MMA scanning (35.3%), with no significant agreement between these methods (κ=-0.12; P=0.163). HPS is a common complication of cirrhosis in children. A combination of clinical and imaging criteria should be used to diagnose HPS.

Związek między zakażeniem Helicobacter pylori a marskością wątroby u dzieci

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Zahmatkeshan M, Matani R, Asadian F. Association between Helicobacter pylori infection and cirrhosis in children. Medical Studies/Studia Medyczne. 2019;35(3):198-202. doi:10.5114/ms.2019.88417. APA Zahmatkeshan, M., Matani, R., & Asadian, F. (2019). Association between Helicobacter pylori infection and cirrhosis in children. Medical Studies/Studia Medyczne, 35(3), 198-202. https://doi.org/10.5114/ms.2019.88417 Chicago Zahmatkeshan, Mozhgan, Rahman Matani, and Fatemeh Asadian. 2019. "Association between Helicobacter pylori infection and cirrhosis in children". Medical Studies/Studia Medyczne 35 (3): 198-202. doi:10.5114/ms.2019.88417. Harvard Zahmatkeshan, M., Matani, R., and Asadian, F. (2019). Association between Helicobacter pylori infection and cirrhosis in children. Medical Studies/Studia Medyczne, 35(3), pp.198-202. https://doi.org/10.5114/ms.2019.88417 MLA Zahmatkeshan, Mozhgan et al. "Association between Helicobacter pylori infection and cirrhosis in children." Medical Studies/Studia Medyczne, vol. 35, no. 3, 2019, pp. 198-202. doi:10.5114/ms.2019.88417. Vancouver Zahmatkeshan M, Matani R, Asadian F. Association between Helicobacter pylori infection and cirrhosis in children. Medical Studies/Studia Medyczne. 2019;35(3):198-202. doi:10.5114/ms.2019.88417.

Liver Cirrhosis of the Viral Etiology in Children

The structure of liver cirrhosis (LC) in children of Uzbekistan was studied. 135 children with viral etiology of liver cirrhosis at the age of 7—15 years of life were examined. It was established that in the structure of viral liver cirrhosis in children, mixed etiology prevails (77.1%) with a predominance of HDV infection (B + C + D — 35.6% and B + D — 23.7%). Mixed infection is considered as a predictor of disease progression, especially in cases of overlap of HDV infection, which was also expressed by the frequent identification of the decompensated stage of the liver cirrhosis C-class of Child-Pugh and complications. Levels of N-terminal propeptides and C-terminal telopeptides of type I collagen in children with liver cirrhosis can serve as markers of compensation and progression of the disease.

Erectile dysfunction in compensated liver cirrhosis

BackgroundData on erectile dysfunction (ED) in cirrhotic patients are limited as yet. Aim of this study was to investigate the prevalence of ED and the factors potentially involved in its development in compensated cirrhosis. MethodsWe prospectively enrolled 102 male (mean age 63 ± 10 years) affected by cirrhosis in Child–Pugh Class A. The following questionnaires were used: simplified International Index of Erectile Function (IIEF-5) Questionnaire, Centre of Epidemiologic Studies Depression Scale and ANDROTEST. ResultsED was found in 57/102(55.9%) patients, and was mild, moderate and severe in 21(36.8%), 6(10.5%) and 30(52.6%) subjects, respectively. ED patients were significantly older than those without (66 ± 10 vs 60 ± 10,p = 0.006); ED prevalence gradually increased with age. There was no statistically significant difference between patients with and without ED concerning the coexistence of diabetes, hypertension, and cardiovascular disease. Age(p = 0.040) and serum haemoglobin(p = 0.027) were identified as predictors of ED on multivariate analysis. Liver-related factors and pharmacological treatment, including β-blockers, were not associated with the presence of ED. ConclusionsIn patients with compensated liver cirrhosis, even in concomitance with other chronic comorbidities, the prevalence of ED is not markedly different from the general population. Compensated cirrhosis per se is not a risk factor for ED occurrence. Older age and low haemoglobin values are significantly associated with ED in cirrhotics.

A study on clinico-etiological profile of chronic liver disease in children between 1year to 14 years of age

Introduction: Chronic liver diseases(CLD) account for 1 to 5% of paediatric ward admissions and upto 20% of ward mortality in our country. Now a day Indian childhood cirrhosis is a rarity, whereas diseases likechronic hepatitis, Wilsons disease and biliary atresia are diagnosed with increasing frequency and therefore became relatively important forms of paediatric liver disease. Methodology: The study was done to determine the clinico-etiological profile of chronic liver disease in children 1 year to 14 years. This is a prospective case-controlled study done over a period of two years. Various clinical, biochemical and radiographic parameters pertaining to chronic liver disease were studied. Results: About4 0 cases were studied. CLD was found to be prevalent in 5-10 years of age group. Male were more affected than female. Jaundice was the most common presenting feature.Hepatomegaly, Ascitis, Splenomegaly were thecommonest presenting signs. Conclusion: CLD is not uncommon condition in children. It constitutes 18.34% of the patients of the with liver disease in our region. Wilson’s disease was the most common aetiology apart from idiopathic which constitute 52.5% of the cause.

Case of Neonatal Fatality from Neuromuscular Variant of Glycogen Storage Disease Type IV.

Glycogen storage disease type IV (GSD-IV), or Andersen disease, is a rare autosomal recessive disorder that results from the deficiency of glycogen branching enzyme (GBE). This in turn results in accumulation of abnormal glycogen molecules that have longer outer chains and fewer branch points. GSD-IV manifests in a wide spectrum, with variable phenotypes depending on the degree and type of tissues in which this abnormal glycogen accumulates. Typically, GSD-IV presents with rapidly progressive liver cirrhosis and death in early childhood. However, there is a severe congenital neuromuscular variant of GSD-IV that has been reported in the literature, with fewer than 20 patient cases thus far. We report an unusual case of GSD-IV neuromuscular variant in a late preterm female infant who was born to non-consanguineous healthy parents with previously healthy children. Prenatally, our patient was found to have decreased fetal movement and polyhydramnios warranting an early delivery. Postnatally, she had severe hypotonia and respiratory failure, with no hepatic or cardiac involvement. Extensive metabolic and neurological workup revealed no abnormalities. However, molecular analysis by whole-exome sequencing revealed two pathogenic variants in the GBE1 gene. Our patient was thus a compound heterozygote of the two pathogenic variants: one of these was inherited from the mother [p.L490WfsX5 (c.1468delC)], and the other pathogenic variant was a de novo change [p.E449X (c.1245G>T)]. As expected in GSD-IV, diffuse intracytoplasmic periodic acid-Schiff-positive, diastase-resistant inclusions were found in the cardiac myocytes, hepatocytes, and skeletal muscle fibers of our patient.

Quantum Language of MicroRNA: Application for New Cancer Therapeutic Targets.

MicroRNA (miRNA) is the noncoding gene: therefore, the miRNA gene inheritably controls protein gene expression through transcriptional and post-transcriptional levels. Aberrant expression of miRNA genes causes various human diseases, especially cancers. Although cancer is a complex disease, cancer/miRNA implication has yet been grasped from the perspective of miRNA profile in bed side. Since miRNA is the mobile genetic element, the clinical verification of miRNAin microvesicle of blood is too much straggle to predict potential cancer/miRNA associations without bioinformatical computing. Further, experimental investigation of miRNA/cancer pathways is expensive and time-consuming. While the accumulated data (big data) of miRNA profiles has been on line as the databases in cancers, using the database algorithms for miRNA target prediction have reduced required time for conventional experiments and have cut the cost. Computational prediction of miRNA/target mRNA has shown numerous significant outcomes that are unobtainable only by experimental approaches. However, ID of miRNA in the annotation is an arbitrary number and the ID is not related with miRNA its functions. Therefore, it has not been physicochemically shown why multiple miRNAs in blood or tissues are useful for diagnosis and porgnosis of human diseases or why function of single miRNA in cancer is rendered to oncomir or tumopr suppressor. In addition, it is less cleared why environmental factors, such as temperature, radiation, therapeutic anti-cancer immune or chemical agents can alter the expression of miRNAs in the cell. The ceRNA theory would not be enough for the investigation of such subjects. Given miRNA/target prediction tools, to elucidate such issues with computer simulationwe have previously introduced the quantum miRNA/miRNA interaction as a new scoring using big database. The quantum score was implicated in miRNA synergisms in cancer and participated in the miRNA/target interaction on human diseases. On the other hand, ribosomal RNA (rRNA) is the dominant RNA species of the cells. It is well known that ribosomopathies, such as Diamond-Blackfan anemia, dyskeratiosis congenital, Shwachman-Diamond syndrome, 5q-myelodysplastic syndrome, Treacher Collins syndrome, cartilage-hair hypoplasia, North American Indian childhood cirrhosis, isolated congenital asplenia, Bowen-Conradi syndrome and cancer are caused by altered expression of ribosomal proteins or rRNA genes. We haveproposed the hypothesis thatthe interaction among miRNAs from rRNA and/or other cellular miRNAs would be involved into cancer as the ribosomopathy. Subsequently, we found rRNA-derived miRNAs (rmiRNAs) by using the sequence homology search(miPS) with miRNA database(miRBase). Further, the pathwayrelated with cancer between rmiRNA/target protein gene was predicted by miRNA entangling target sorting (METS) algorithm. In this chapter, we describe about the usage of in silico miRNA identification program, miRNA/target prediction search through the database and quantum language of miRNAby the METS, and the ontology analysis. In particular, the METS algorithm according to the quantum value would be useful simulator to discover a new therapeutic target aganist cancer. It mayalso partly contribute to the elucidation of complex mechanisms and development of agents of anti-cancer.

Liver and systemic hemodynamics in children with cirrhosis: Impact on the surgical management in pediatric living donor liver transplantation.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P < 0.001) and liver CPA (P = 0.005). Median portosystemic gradient was 14.5 mm Hg in children with cirrhosis and positively correlated with PELD (P < 0.001). Portal vein (PV) hypoplasia was observed mainly in children with BA (P = 0.02). Systemic hemodynamics were not altered in our children with cirrhosis. Twenty-one children met the intraoperative criteria for PV reconstruction using a portoplasty technique during the LT procedure and had a smaller PV diameter at pretransplant Doppler ultrasound (median = 3.4 mm; P < 0.001). Cirrhosis in children appears also as a hemodynamic disease of the liver, correlated with cirrhosis severity. Surgical technique for PV reconstruction during LT was adapted accordingly. Liver Transplantation 23 1440-1450 2017 AASLD.

Early case of childhood cirrhosis in 1876

Early case of childhood cirrhosis in 1876

The Canadian Biliary Atresia Registry: Improving the care of Canadian infants with biliary atresia

Biliary atresia is the most common cause of end-stage liver disease and liver cirrhosis in children, and the leading indication for liver transplantation in the paediatric population. There is no cure for biliary atresia; however, timely diagnosis and early infant age at surgical intervention using the Kasai portoenterostomy optimize the prognosis. Late referral is a significant problem in Canada and elsewhere. There is also a lack of standardized care practices among treating centres in this country. Biliary atresia registries currently exist across Europe, Asia and the United States. They have provided important evidence-based information to initiate changes to biliary atresia care in their countries with improvements in outcome. The Canadian Biliary Atresia Registry was initiated in 2013 for the purpose of identifying best standards of care, enhancing public education, facilitating knowledge translation and advocating for novel national public health policy programs to improve the outcomes of Canadian infants with biliary atresia.

Prognosis analysis of hepatitis B cirrhosis patients with type 2 diabetes mellitus

Objective To investigate the impact of type 2 diabetes mellitus (DM) on the progression and prognosis of patients with hepatitis B cirrhosis. Methods A total of 247 hospitalized patients with hepatitis B cirrhosis in Child A and B phases were collected from January 2008 to March 2009 in 9th Hospital of Nanchang. Based on type 2 DM diagnosis, the hepatitis B cirrhosis patients were divided into non-DM group (n=168) and DM group (n=79). Occurrence and survival rate of hepatic decompensation, cirrhosis complications, cardiovascular disease and hepatocellular carcinoma were retrospective analyzed. Comparative t-test was used for measurement data, χ2 test was used for count data and Log-rank test was used for survival rate. Multivariate analysis was conducted by Logistic regression. Results In DM group, 68 cases (86.1%) developed hepatic decompensation, 63 cases (79.7%) of cirrhosis complications, 11 cases (13.9%) of cardiovascular diseases and 19 cases (24.1%) of hepatocellular carcinoma, which were all higher than those in non-DM group (118 cases [70.2%] of hepatic decompensation [χ2=5.930, P=0.015]; 106 cases [63.1%] of cirrhosis complications [χ2=6.895, P=0.009]; only 1 case [0.6%] of cardiovascular disease [χ2=20.652, P=0.000]; and 18 cases [10.7%] of hepatocellular carcinoma [χ2=7.504, P=0.006]). The differences were all statistically significant. Survival rates for 2-year, 4-year and 6-year follow-up in DM group were all obviously lower than those of non-DM group (86.1% vs 96.3%, 56.5% vs 77.5%, 17.4% vs 39.2%, respectively), and the difference was statistically significant (χ2=14.208, P=0.000). The mortalities of cirrhosis complication (36.7% vs 21.4%; χ2=6.470, P=0.011) and hepatocellular carcinoma (12.7% vs 3.6%; χ2=7.324, P=0.007) in DM group were both significantly higher than those in non-DM group. After adjusting for sex, age, alcohol use and Child score, DM remained an independent predictor for hepatocellular carcinoma (odds ratio=3.232, 95% confidence interval: 1.378-7.580; P=0.007). Conclusion Type 2 DM could increase the incidences of hepatic decompensations, cirrhosis complications, hepatocellular carcinoma and cardiovascular diseases, while reduce the survival rate of patients with cirrhosis, which has an serious impact on the prognosis of hepatitis B cirrhosis patients. Key words: Hepatitis B; Liver cirrhosis; Diabetes mellitus, type 2; Prognosis

Coagulopathy and transfusion therapy in pediatric liver transplantation.

Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, "developmental hemostasis", demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the "cell based model of coagulation", takes into account the interaction between plasma proteins and cells. In the last, the concept of "rebalanced coagulation" highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations.

Hepatitis B virus basal core promoter/precore mutants and association with liver cirrhosis in children with chronic hepatitis B virus infection

We investigated 168 children and analysed the virological characterization and association with disease progression in children with hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutants. Among 168 patients with HBV infection (aged 0.5–18 years old, mean 10.1), 86 of them had HBV-related liver cirrhosis (LC) and 82 had HBV-related chronic hepatitis B (CHB). A direct sequencing method was employed to determine the HBV genotypes and the mutations in BCP/PC regions. In all, 133 of them were infected with genotype C viruses (79.17%); only 35 patients (20.83%) were infected with genotype B viruses. Both LC patients and CHB patients had significantly higher ratios of genotype C when compared with the ratios of genotype B (83.7%–16.3% versus 74.4%–25.6%). For patients with CHB, the prevalence of BCP/PC wild-type viruses was 52.4%; but this was only 4.7% in patients with LC. The C1653T, T1753C, A1762T/G1764A and G1896A mutations had a significantly higher prevalence in patients with LC. Among all the patients with genotype B viruses, those with LC had lower HBV DNA levels and higher G1899A mutation frequency than patients with CHB. Among all the patients with genotype C viruses, the patients with LC had higher prevalence of C1653T, A1762T/G1764A and G1896A mutation frequency, higher hepatitis B e antigen (HBeAg) -negative rates, lower viral load, lower elevated alanine aminotransferase and lower anti-HBe positive rates than CHB patients. The HBV BCP/PC variants were more common in HBeAg-negative LC patients than in the CHB group (BCP, 53.4% versus 15.6%; PC, 18.6% versus 3.7%, respectively, p < 0.001). Patients with HBV genotype C viruses, high viral load and C1653T, A1762T/G1764A, G1896A mutant viruses, were more susceptible to developing LC.

Editorial Comment on: D. Schreiber-Dietrich, M. Pohl, X.W. Cui, B. Braden, C.F. Dietrich, L. Chiorean Perihepatic lymphadenopathy in children with chronic viral hepatitis

The article entitled Perihepatic lymphadenopathy in children with chronic viral hepatitis(1) is an original paper of high clinical relevance – viral hepatitis B and C are the main causes of chronic hepatitis and liver cirrhosis in children. Based on ultrasound findings, the authors assessed the presence of the perihepatic lymph nodes and their morphology in 49 children with chronic viral hepatitis B and C (38 and 11 children, respectively). The authors hoped that this investigation would help establish a new, non-invasive marker enabling screening examinations to be conducted in children with chronic viral hepatitis. In adults, a correlation was found between the activity of hepatitis and the morphology of the lymph nodes in a US examination, but such a correlation has, until now, not been reported in children(2–4). The results of the study have a clinically significant aspect – the loops of the hepatoduodenal ligament are relatively readily available in a transabdominal examination, and ultrasonography is an inexpensive and safe method to be conducted in children. The authors assumed that the lymph nodes with the size of over 14 mm in the long axis were pathologically enlarged. In a US examination, such nodes were visualized in 70% of children with viral hepatitis and in 11% of healthy children. Based on the studies conducted, it was concluded that the general volume of the perihepatic lymph nodes is greater in children with chronic hepatitis in a statistically significant way (p < 0.05), compared to healthy children: 1.0 ± 1.2 mL (0.1–5.4 mL) vs 0.1 ± 0.1 mL (0.0–0.4 mL). Ultrasonography demonstrated a moderate level of sensitivity (70%) and NPV (75%), and considerable specificity (89%) and PPV (86%) in detecting enlarged perihepatic lymph nodes in children with chronic viral hepatitis. Enlarged lymph nodes of the hepatoduodenal ligament were present in patients with both chronic hepatitis B and C. There were no significant differences in the sensitivity and specificity levels of ultrasonography between the two types of hepatitis (hepatitis B: sensitivity 69%, specificity 89%; hepatitis C: sensitivity 70%, specificity 89%), but the method was characterized by superior accuracy in confirming hepatitis B (PPV 83%) compared to hepatitis C (PPV merely 58%). However, ruling out chronic viral hepatitis based on US findings was much more accurate in children with hepatitis C than in children with hepatitis B (NPV 93% vs 79%). The article summarized above is a very good example of research methodology, particularly for young scientists. The design is exemplary: the study is prospective, randomized; the inclusion and exclusion criteria are clearly specified. The methods involve the principles of so-called good clinical practice. The accurate assessment of the repeatability of size and volume measurements in a US examination must be emphasized. The evidence for a high repeatability of the measurements is an additional argument for including the perihepatic lymph node assessment into everyday clinical practice involving the treatment of children with chronic viral hepatitis B and C. In the Discussion, the authors prove how innovative their results are and indicate the path for further research – the possibility of monitoring the therapy of chronic viral hepatitis using size measurements of the perihepatic lymph nodes. Moreover, the authors also mention other methods enabling perihepatic lymph node imaging, such as CT and MRI. However, the argument concerning limited possibilities of the lymph node reconstruction in the age of multi-slice CT seems unconvincing. Furthermore, the methods of conducting US examinations applied by the authors seem lacking: the authors used a 3.5 MHz transducer in all patients irrespective of their age (1–17). Yet our experience and literature guidelines suggest that probes of higher frequency should be used for the assessment of visceral lymph nodes in younger children. The results of the measurements of the size and volume of the perihepatic lymph nodes in children with chronic viral hepatitis also raise questions regarding their accurate assessment (configuration of the hilum, blood supply and direction of flow) as well as a possible relationship of these features with the activity of the disease. Further investigations should continue the issues started in this article.

INDIAN CHILDHOOD CIRRHOSIS: CASE REPORT AND PEDIATRIC DIAGNOSTIC CHALLENGES

Introduction: Indian childhood cirrhosis is a chronic liver disease usually seen in paediatric age group and is unique to the Indian subcontinent. The definitive causative factor for the disease is not found till now but excess copper ingestion has been associated with it.Case presentation: An Indian origin one and half year old premorbidly normal male child presented with history of gradual distension of abdomen for 6 months and jaundice, generalized body swelling, high colour urine for 20 days. There was no history of any bleeding or feature suggestive of hepatic encephalopathy. On physical examination child was icteric, pale and had anasarca, massive hepatosplenomegaly and ascites. The child was evaluated for various causes of hepatic failure in pediatric age group including infective, metabolic and autoimmune etiologies. Unfortunately the child succumbed to the illness. The post-mortem liver biopsy and copper estimation cleared the air, revealing Indian childhood cirrhosis as the underlying etiology.Conclusion: Though Indian childhood cirrhosis is a rare entity and reported less frequently in literature, the treating pediatrician should keep this as a differential in case of pediatric hepatic failure. The liver biopsy and hepatic copper estimation are the gold standard diagnostic tests for diagnosing Indian Childhood cirrhosis.

Cirrhosis in children and adolescents: An overview.

Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition.

Hepatic Hemodynamics in Cirrhotic Children: Correlation to PELD and Portal Vein Complications After Liver Transplantation.

Background Liver hemodynamic (LH) disturbances and portal vein (PV) complications are frequently observed in pediatric liver transplantation (LT). We hypothesized that cirrhosis in children is associated with LH features which could lead to PV complications after LT. Methods We retrospectively analyzed 198 LT recipients (median age: 1.6 year), including 130 biliary atresia (BA). Pre-LT hemodynamics were studied using Doppler ultrasound, and correlated with the incidence of post-LT PV complications. In children with BA-related PV hypoplasia, the technique used for PV reconstruction was correlated with the incidence of post-LT PV complications. Moreover, intraoperative flowmetry of LH was studied prospectively at LT in 31 cirrhotic children (median age: 0.9 year), including 23 BA. Results At retrospective analysis, hepatic arterial resistance index ≥ 1 at pre-LT ultrasound was associated with a higher rate of PV complications (p=0.041). In children with BA-related PV hypoplasia, the portoplasty technique alleviated the extra risk of PV complications (6.2% with portoplasty versus 19.3% without portoplasty). The prospective hemodynamic studies showed that: (1) pediatric cirrhosis was associated with a reduction of pre-LT total liver flow of more than 60% (median: 35 ml/min/100gr of liver), compared to expected values (100 ml/min/100gr); (2) this reduction of total liver flow was correlated with PELD (tau=-0.259; p=0.041). Conclusions Pediatric cirrhosis is associated to severe LH disturbances, which are correlated with PELD. Pre-LT hemodynamic assessment may help to predict, and efficiently manage liver vascular anomalies in pediatric LT, including BA-related PV hypoplasia.

Hepatic vena cava syndrome: a common cause of liver cirrhosis in children in Nepal.

Disease of hepatic portion of the inferior vena cava (IVC) now renamed hepatic vena cava syndrome (HVCS) is an insidious onset chronic disease characterized by recurrent acute exacerbations and development of cavo-caval collaterals. In adults it is complicated by high incidence of liver cirrhosis. Aim of this study was to assess the incidence of liver cirrhosis in children with HVCS and discuss its pathogenesis. One hundred and seventy eight children with HVCS were followed up with ultrasonography (USG), routine hematology and liver tests. During acute exacerbations, cultures of blood and ascitic fluid for aerobic microorganisms were also done. Diagnosis of liver cirrhosis was based on transformation of the liver parenchymal echo-texture from normal to uniformly coarse with rounded edges in follow-up USG It was confirmed by direct inspection of the liver or by biopsy in six. The duration from disease onset to detection of liver cirrhosis was also assessed. HVCS was seen in children from poor socio-economic background. Forty nine patients (27.5%) developed liver cirrhosis within a few months to a few years of onset of the disease. Development of cirrhosis was related to frequency or severity of acute exacerbations and not to duration of illness or severity of the caval lesion. The cause of cirrhosis in HVCS was the ischemic injury of the hepatocytes and sinusoids following thrombosis of the IVC and/or intra-hepatic veins during severe acute episodes or exacerbations precipitated by bacterial infection. Since such acute exacerbations are amenable to medical treatment, HVCS may be a cause of preventable liver cirrhosis in developing countries.

Role of alpha‐1 antitrypsin in human health and disease

Alpha-1 antitrypsin (AAT) deficiency is an under-recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000-1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000-10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad-spectrum anti-inflammatory, immunomodulatory, anti-infective and tissue-repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.