Ischemia-Modifi ed Albumin Levels in Children with Chronic Liver Disease

( Murat Cakir ),( Suleyman Caner Karahan ),( Ahmet Mentese ),( Elif Sag ),( Umit Cobanoglu ),( Tugcin Bora Polat ),( Erol Erduran ) 대한소화기기능성질환·운동학회 2012 Gut and Liver Vol.6 No.1

Background/Aims: Ischemia-modifi ed albumin (IMA) levels have been shown to correlate with the severity of liver failure in adults. However, the role of IMA levels has not been evaluated in children with chronic liver disease (CLD). We analyzed the clinical significance of IMA levels in children with CLD. Methods: Thirty-three children with CLD and 33 healthy children were included in the study. Blood was collected to analyze biochemical parameters, oxidant status, and IMA. Liver biopsies were re-evaluated for liver fibrosis; severe fibrosis (SF) was defi ned as fi brosis stage ≥4. Results: The IMA and and IMA to albumin ratios (IMARs) were signifi cantly higher in children with CLD than in those without (IMA: 0.545±0.095 vs 0.481±0.062, p=0.003; IMAR: 0.152±0.046 vs 0.126±0.018, p=0.04). The IMAR was positively correlated with the pediatric end-stage liver disease score (p=0.03, r=0.503) and fibrosis score (p=0.021, r=0.400). Patients with SF had higher IMARs compared to patients with mild fi brosis (0.181±0.056 vs 0.134±0.025, p=0.003). The area under the receiver operation curve (AUROC) for predicting SF was 0.78 (p=0.006). Using a cutoff ratio value of 0.140, the sensitivity and specificity were 84% and 70%, respectively. The AUROC for predicting the need for liver transplantation and/or death was 0.82 (p=0.013). With a cutoff value of 0.156, the sensitivity and specifi city was 83% and 82%, respectively. Kaplan-Meier analysis revealed increased morbidity and/or mortality in the group with an IMAR>0.156 (50% vs 4.3%, p=0.005). Conclusions: IMARs have been shown to provide important clues in predicting the fi brosis stage of the disease and determining the outcome in children with CLD. (Gut Liver 2012;6:92-97)

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy

Cakir, Murat,Senyuva, Sukran,Kul, Sibel,Sag, Elif,Cansu, Ali,Yucesan, Fulya Balaban,Yaman, Serap Ozer,Orem, Asim The Korean Society of Pediatric Gastroenterology 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.2

Purpose: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. Methods: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. Results: All parameters of neurocognitive development and serum calcium ($9.6{\pm}0.9mg/dL$ vs. $10.4{\pm}0.3mg/dL$, p<0.05) and magnesium ($2.02{\pm}0.27mg/dL$ vs. $2.2{\pm}0.14mg/dL$, p<0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition ($1.33{\pm}0.22$ vs. $1.18{\pm}0.22$, p<0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p<0.05, r=0.381). Conclusion: Calcium supplementation may improve neurocognitive development in malnourished infants.

Primary Immunodeficiencies in Children Initially Admitted with Gastrointestinal/Liver Manifestations

Murat Cakir,Nalan Yakici,Elif Sag,Gulay Kaya,Ayşenur Bahadir,Alper Han Cebi,Fazil Orhan 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.4

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5–204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

Liver Involvement in Children with Alpha-1 Antitrypsin Deficiency: A Multicenter Study

Cakir, Murat,Sag, Elif,Islek, Ali,Baran, Masallah,Tumgor, Gokhan,Aydogdu, Sema The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.2

Purpose: Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. Methods: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). Results: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. Conclusion: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy

Murat Cakir,Sukran Senyuva,Sibel Kul,Elif Sag,Ali Cansu,Fulya Balaban Yucesan,Serap Ozer Yaman,Asim Orem 대한소아소화기영양학회 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.2

Purpose: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. Methods: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. Results: All parameters of neurocognitive development and serum calcium (9.6±0.9 mg/dL vs. 10.4±0.3 mg/dL, p <0.05) and magnesium (2.02±0.27 mg/dL vs. 2.2±0.14 mg/dL, p <0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition (1.33±0.22 vs. 1.18±0.22, p <0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels ( p <0.05, r=0.381). Conclusion: Calcium supplementation may improve neurocognitive development in malnourished infants.

Intussusception: As the Cause of Mechanical Bowel Obstruction in Adults

( Murat Cakir ),( Ahmet Tekin ),( Tevfik Kucukkartallar ),( Metin Belviranli ),( Ebubekir Gundes ),( Yahya Paksoy ) 대한소화기학회 2013 대한소화기학회지 Vol.61 No.1

Background/Aims: Intussusception in adults is rarely seen and causes misdiagnosis due to its appearance with various clinical findings. The cause of intussusception in adults is frequently organic lesions. In this study, the underlying etiologic factors, diagnostic methods and alternative methods of treatment are discussed in the light of the literature. Methods: In this study, a retrospective evaluation was performed on 47 cases with the diagnoses of intussusception, who were operated on for bowel obstruction between 1990-2011 in Department of Surgery of Necmettin Erbakan University Meram Medical Faculty. Data related to presentation, diagnosis, treatment and pathology were analyzed. Results: Twenty-four of the patients (51%) were female, and 23 were male (49%). Mean age (year) was 49 (range: 23-78) in female group, and 50 (range: 17-72) in male group. All patients presented mechanical bowel obstruction findings and underwent operation. Intussusception was caused by benign and malignant tumors in 38 patients, and other reasons in 3 cases. No reason could be determined in the other 6 cases. Only small intestine resection was applied in 29 cases, and large intestine resection was also applied in 17 cases. Reduction and fixation surgery was performed in one patient. No postoperative mortality was observed. Conclusions: Adult intussusception remains a rare cause of abdominal pain. Diagnosis of intussusception in adults is still difficult. Main treatment was surgical in most cases. (Korean J Gastroenterol 2013;61:17-21)

Disseminated Cytomegalovirus Infection and Protein Losing Enteropathy as Presenting Feature of Pediatric Patient with Crohn's Disease

Cakir, Murat,Ersoz, Safak,Akbulut, Ulas Emre The Korean Society of Pediatric Gastroenterology 2015 Pediatric gastroenterology, hepatology & nutrition Vol.18 No.1

We report a pediatric patient admitted with abdominal pain, diffuse lower extremity edema and watery diarrhea for two months. Laboratory findings including complete blood count, serum albumin, lipid and immunoglobulin levels were compatible with protein losing enteropathy. Colonoscopic examination revealed diffuse ulcers with smooth raised edge (like "punched out holes") in the colon and terminal ileum. Histopathological examination showed active colitis, ulcerations and inclusion bodies. Immunostaining for cytomegalovirus was positive. Despite supportive management, antiviral therapy, the clinical condition of the patient worsened and developed disseminated cytomegalovirus infection and the patient died. Protein losing enteropathy and disseminated cytomegalovirus infection a presenting of feature in steroid-naive patient with inflammatory bowel disease is very rare. Hypogammaglobulinemia associated with protein losing enteropathy in Crohn's disease may predispose the cytomegalovirus infection in previously healthy children.

Disseminated Cytomegalovirus Infection and Protein Losing Enteropathy as Presenting Feature of Pediatric Patient with Crohn’s Disease

Murat Cakir, Safak Ersoz,Ulas Emre Akbulut 대한소아소화기영양학회 2015 Pediatric gastroenterology, hepatology & nutrition Vol.18 No.1

We report a pediatric patient admitted with abdominal pain, diffuse lower extremity edema and watery diarrhea for two months. Laboratory findings including complete blood count, serum albumin, lipid and immunoglobulin levels were compatible with protein losing enteropathy. Colonoscopic examination revealed diffuse ulcers with smooth raised edge (like "punched out holes") in the colon and terminal ileum. Histopathological examination showed active colitis, ulcerations and inclusion bodies. Immunostaining for cytomegalovirus was positive. Despite supportive man-agement, antiviral therapy, the clinical condition of the patient worsened and developed disseminated cytomegalovi-rus infection and the patient died. Protein losing enteropathy and disseminated cytomegalovirus infection a present-ing of feature in steroid-naive patient with inflammatory bowel disease is very rare. Hypogammaglobulinemia asso-ciated with protein losing enteropathy in Crohn's disease may predispose the cytomegalovirus infection in previously healthy children.

Liver Involvement in Children with Αlpha-1 Antitrypsin Deficiency: A Multicenter Study

Murat Cakir,Elif Sag,Ali Islek,Masallah Baran,Gokhan Tumgor,Sema Aydogdu 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.2

Purpose: Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. Methods: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). Results: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. Conclusion: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.

The effects of flavanoid on the treatment of hepatopulmonary syndrome

Talha Atalay,Murat Cakir,Ahmet Tekin,Tevfik Kucukkartallar,Suleyman Kargin,Adil Kartal,Adnan Kaynak 대한외과학회 2013 Annals of Surgical Treatment and Research(ASRT) Vol.85 No.5

Purpose: Hepatopulmonary syndrome is an arterial oxygenation disorder brought about by advanced liver failure and pulmonary vascular dilatations. The reason why hypoxia develops in hepatopulmonary syndrome depends on the broadening of perialveolar capillary veins. Our study aims to investigate the effects of Flavanoid on hepatopulmonary syndrome through its inhibition of nitric oxide. Methods: Three groups, each having 8 rats, were formed within the scope of our study. Group I (the control group) only received laparatomy, group II received choledoch ligation, and group III was administered Flavanoid (90% flavonoid diosmin, 10% flavonoid hesperidin) following choledoch ligation. The rats were administered Flavanoid at week two following choledoch ligation. The rats’ livers and lungs were examined histopathologically following a five-week follow-up and the perialveolar vein diameters were measured. Arterial blood gases and biochemical parameters were evaluated. Results: It was seen that fibrosis and oxidative damage in the liver with obstructive jaundice as well as hypoxia with pulmonary perialveolar vein sizes were significantly lower than the other group with cirrhosis formed through the administration of Flavanoid. Conclusion: We have concluded that Flavanoid administration might be useful in the treatment of hypoxia in hepatopulmonary syndrome and the delay of cirrhosis contraction.