LIVER CIRRHOSIS IN CHILDREN

Background : Liver cirrhosis is one of the major causes of hospitalization and mortality in children. A wide spectrum of disorders including developmental abnormalities, infections, metabolic and genetic disorders can lead to liver cirrhosis in pediatric patients. Determination of its etiology is important for treatment, prevention of progressive liver damage, family counseling and prioritizing liver transplantation. The aim of this study is to evaluate etiological and prognostic aspects of liver cirrhosis in children at the pediatrics department at the university hospital center of Marrakech. Methods : We included all cirrhotic children under the age of 15 who were hospitalized in the gastro-pediatric department at the University Hospital Center of Marrakech over a period from January 2012 to December 2018 in this retrospective study. The etiology of cirrhosis was determined based on clinical results, laboratory tests, imaging studies mainly by ultrasound and histopathological examination of the liver biopsy. Results : A total of 78 cirrhotic children aged 1


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Complications of cirrhosis include jaundice, ascites, gastrointestinal variceal bleeding, and hepatic encephalopathy, whose presence is indicative of decompensated disease. 8- 10 Other reported complications include edema, 11 spontaneous bacterial peritonitis, 12 and hepatopulmonary 13 and hepatorenal syndromes. 14 For suitable treatment of liver cirrhosis the need for early diagnosis and etiological definition should be emphasized. 15 Thus, the aim of this study is to report the causes of liver cirrhosis and evaluate its prognostic.

Materials and Methods:-
We included all cirrhotic children under the age of 15 who were hospitalized in the gastro-pediatric department at the University Hospital Center of Marrakech over a period from January 2012 to December 2018. Cirrhosis was diagnosed according to clinical, radiological, or histological criteria.
All patients were clinically examined and a data gathering form was completed that contained demographic, clinical and paraclinical data.
The etiology of cirrhosis was identified according to clinical, biological, radiological and in particular ultrasound results and based on histological data from the liver biopsy.
Within the framework of the etiological assessment, a panoply of assessment can be requested, among which we quote those available in our country: 1. Blood count, direct and indirect total bilirubin, Alkaline phosphatases, gamma glutamyl transferase, transaminases, Prothrombin level, 2. Electrophoresis of plasma proteins, if necessary alpha 1 antitrypsin weight determination, 3. TORCH serologies, hepatitis B and C serologies, 4. Ammonemia and lactatemia, chromatography of blood and urinary amino acids, determination of galactose 1 phosphate, testing for succinyl acetone in the urine, 5. Wilson disease assessment: ceruleoplasmin and 24 hour cupruria, 6. Autoimmune hepatitis tests: Anti-nuclear antibodies, Anti-smooth muscle antibodies, Anti-LKM antibodies, 7. abdominal ultrasound, X-ray of the dorsolumbar spine, 8. Ophthalmologic examination in search of posterior embryotoxon and Kayser Fleischer ring.

Results:-
Seventy eight (78) files were retained including 43 boys (55%) and 35 girls (45%). The age of our patients varied from one month to 12 years with an average of 3 years and 5 months.
Jaundice was the most frequent associated clinical sign (80% of cases), digestive hemorrhage was present in 60% of cases, pruritus in 3 patients. The clinical examination showed the presence of hepatomegaly in 90%, splenomegaly in 85% of patients, ascites in 60% of patients, collateral venous circulation in 85% of patients.
Biologically, cytolysis and cholestasis were present with varying degrees, liver function was disturbed in 70% of patients in our series with an average Prothrombin level of 37% ranging from an incoagulable Prothrombin level to 100%, the mean total bilirubin level was 169.4 mg/ l predominantly combined with 143.6 mg / l.
The abdominal ultrasound showed a heterogeneous dysmorphic liver in 77 cases, a steatotic liver in one case.
At the end of the various investigations, an etiological diagnosis could be established in 69% of the cases, it was 20 cases of Wilson's disease, biliary atresia in 16 cases, 5 cases of glycogenosis, 3 cases of PFIC, 2 sclerosing cholangitis, 2 cases of tyrosinemia, 2 cases of alpha 1 antitrypsin deficiency, one case of hepatitis B, one case of autoimmune hepatitis, one case of cirrhosis on celiac disease and one case of hemochromatosis. In 31% of cases, the cause of cirrhosis was unknown.
Due to hepatocellular insufficiency and hemostasis disorders, liver biopsy puncture was only performed in 9 patients, confirming the diagnosis of cirrhosis and suggesting the cause in 3 cases: 3 cases of atresia of the bile ducts.

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The death rate in our series was 33% with the main cause of gastrointestinal bleeding. All data were analyzed by SPSS for Windows (version 20.0).

Discussion:-
Liver cirrhosis is the most common hepatic cause for hospitalization in adults' gastroenterology and hepatology wards and also the third leading gastrointestinal causes of death in Iran. 16 Although rather uncommon and multifactorial in etiology, liver cirrhosis is a severe and often rapidly fatal disease in pediatric patients. There is little epidemiological information regarding etiology of liver cirrhosis in children and it's chang over time.
Recently this center has become an active pediatric liver transplant center in the Middle East region with more than 70 pediatric liver transplants annually, thus the high number of subjects with Wilson disease might be attributed to referrals from other parts of the country. In a recent study from Iran the most common hepatic diseases among inpatients were hepatitis B virus (HBV) and cryptogenic or non-alcoholic fatty liver disease induced cirrhosis. 17 In another study from Southern Iran HBV infection was the major cause for cirrhosis and ascites was the most common complication in adult patients. 18 The mean PELD/MELD scores in this study was14.2 that is comparable with 15.5 in the Behroozian R et al series. 19 In a Tunisian study on 36 girls and 35 boys with cirrhosis, jaundice and hepatomegaly were the most frequent clinical signs. Regarding the etiology of cirrhosis, biliary causes (including biliary atresia, choledocal cysts, and progressive familial intrahepatic cholestasis) were diagnosed as the most frequent (40%), causes followed by metabolic diseases that included hepatorenal tyrosinemia, Wilson disease (17%) and post-hepatitis cirrhosis (17%). In 27% of cases, no etiology was found. 20 The authors concluded that etiological diagnosis in children with cirrhosis was a problem in their country because of the lack of availability of some specific tests. 20 In Iran, the main indications for liver transplantation in children were reported as Wilson disease (20.3%), cryptogenic cirrhosis (16.7%) and autoimmune cirrhosis (14.5%), 21 which agreed with the results of this study.
In a study from Northern India on 235 children with hepatobiliary disorders, acute hepatitis (28%), chronic liver disease (36%) and neonatal cholestasis syndrome (26%) were presented as the most common causes of liver disease. In Brazil the most common causes of pediatric cirrhosis were biliary atresia (50%), autoimmune disorders (20.5%) and cryptogenic (17.6%). 23 The most common indications for liver transplantation in children in Argentina were biliary atresia (30%), fulminant hepatic failure (27%) and autoimmune cirrhosis (16%). 24 In Oman, progressive familial intrahepatic cholestasis (30%) as well as fibrocystic diseases of the liver and kidneys (21%) were the most common causes of liver cirrhosis. 25 These reports from developing countries recognized that metabolic disorders, cholestatic syndromes and autoimmune hepatitis were the most common causes of cirrhosis in children in these countries.
Also, in Japan the main causes of liver cirrhosis in children who underwent liver transplantation were biliary atresia (72.9%), cryptogenic (8.1%), Budd Chiari syndrome (5.4%), progressive familial intrahepatic cholestasis (5.4%), and Wilson disease (2.7%). 26 In a nationwide survey in Japan to evaluate the etiology of liver cirrhosis, the data from 33379 patients with liver cirrhosis were analyzed at 58 hospitals. These studies have shown completely different causes of liver cirrhosis in children and adults, as the most common cause of liver cirrhosis in adults were viral hepatitis.
This study concluded that metabolic disorders (Wilson disease), cholestatic syndromes (biliary atresia) are the most common causes of cirrhosis in children in our area. Early diagnosis and determining the common causes of cirrhosis in are important for effective treatment and decreasing the rate of complications and mortality.