Peroxiredoxins and Hypoxia-Inducible Factor-1α in Duodenal Tissue: Emerging Factors in the Pathophysiology of Pediatric Celiac Disease Patients.

Celiac disease (CD) is an autoimmune enteropathy. Peroxiredoxins (PRDXs) are powerful antioxidant enzymes having an important role in significant cellular pathways including cell survival, apoptosis, and inflammation. This study aimed at investigating the expression levels of all PRDX isoforms (1-6) and their possible relationships with a transcription factor, HIF-1α, in the small intestinal tissue samples of pediatric CD patients. The study groups consisted of first-diagnosed CD patients (n = 7) and non-CD patients with functional gastrointestinal tract disorders as the controls (n = 7). The PRDXs and HIF-1α expression levels were determined by using real-time PCR and Western blotting in duodenal biopsy samples. It was observed that the mRNA and protein expression levels of PRDX 5 were significantly higher in the CD patients, whereas the PRDX 1, -2, and -4 expressions were decreased in each case compared to the control group. No significant differences were detected in the PRDX 3 and PRDX 6 expressions. The expression of HIF-1α was also significantly elevated in CD patients. These findings indicate, for the first time, that PRDXs, particularly PRDX 5, may play a significant role in the pathogenesis of CD. Furthermore, our results suggest that HIF-1α may upregulate PRDX-5 transcription in the duodenal tissue of CD.

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

Combined immunodeficiency with marginal zone lymphoma due to a novel homozygous mutation in IL-21R gene and successful treatment with hematopoietic stem cell transplantation.

Mutations in the interleukin-21 receptor (IL-21R) gene are recently defined as primary immunodeficiency diseases. IL-21R defects result in combined immunodeficiency by affecting the functions of innate and adaptive immune system components.A six-year-old girl was admitted to our hospital with complaints of chronic diarrhea that started after the newborn period and generalized rash over the last three months. She had severe respiratory distress due to Cytomegalovirus (CMV) pneumonia requiring mechanical ventilation and was diagnosed as combined immunodeficiency at another hospital at the age of four. Her physical examination on admission revealed erythematous rash on cheeks, extremities, gluteal region, and lymph node enlargements in cervical, axillary, and inguinal regions. CMV DNA and stool Cryptosporidium parvum were positive. Marginal zone lymphoma -negative for Epstein-Bar virus- was reported in the lymph node biopsy. Targeted next-generation sequencing Ion AmpliSeq™ primary immunodeficiency panel revealed a novel homozygous IL21R c.132delC (p.Ser45fs) mutation.This case is presented to emphasize that IL21R defects should be considered in the differential diagnosis of the patients with recurrent respiratory infections, chronic diarrhea, C. parvum infection, chronic liver disease, sclerosing cholangitis, and malignancy where early hematopoietic stem cell transplantation (HSCT) is life-saving. A total of eight cases with IL21R gene defects have been reported so far. The significance of this case is that it is the first case of malignancy among the published IL-21R deficient patients successfully treated with HSCT.

Intestinal Protozoan Parasitic Infections in Immunocompromised Child Patients with Diarrhea.

Intestinal protozoan parasites are common causes of infectious diarrhea in children receiving anticancer therapy or undergoing transplantation. Additionally, immunosuppression therapy in such patients may exacerbate the symptoms related to these parasitic infections. The aim of this study was to evaluate the prevalence and diagnostic importance of parasitic protozoan infections in children treated for malignancies or undergoing transplantation, and to highlight the control of intestinal parasitic infections for immunosuppressed patients at a hospital in Izmir, Turkey. In total, 82 stool samples from 62 patients were analyzed by microscopic examination and polymerase chain reaction (PCR) for the presence of coccidian parasites. Our results showed that Cryptosporidium, Cyclospora, and Cystoisospora were present in 22.5% (14/62), 9.6% (6/62), and 3.2% (2/62) of the cases using either method, respectively. The prevalence of these coccidian parasites identified with both methods was 35.4% (20/62). Other intestinal parasites (Blastocystis, Giardia, and Entamoeba coli) were detected in 10 patients. PCR analysis showed the presence of all coccidian parasites in the same stool sample for one patient. Finally, both PCR and microscopic examination of the stools revealed that there is a higher prevalence of Cryptosporidium, Cyclospora, and Cystoisospora in immunocompromised children. These examinations allowed an early start of appropriate antibiotic treatments and led to an increased percentage of correctly treated patients.

Live donor liver transplantation for type 1 tyrosinemia: An analysis of 15 patients.

Type 1 tyrosinemia is a rare metabolic disorder of the tyrosine degradation pathway. Due to the rarity of the disease, the best evidence literature offers is limited to guidelines based on expert opinions and optimal treatment is still a debate. LT serves as a definitive treatment of the defective metabolic pathway in the liver along with other serious disease manifestations such as LF and HCC. Nitisinone is a relatively new agent that is currently recommended for the medical management of the disease. Its mechanism of action is well understood, and efficacy is well established when started presymptomatically. This study aims to evaluate outcomes of 15 patients with type 1 tyrosinemia who underwent LT in nitisinone era and discuss its effect on prevention of HCC. A LT database of 1037 patients was reviewed. Data from 15 patients with type 1 tyrosinemia were retrospectively analyzed. All the patients except one were treated with nitisinone prior to LT. Most common indications for LT were LF and suspicious nodules. Seven patients had HCC. Mortality rate was 20% (n = 3). Nitisinone treatment has opened new horizons in the management of type 1 tyrosinemia, but LT still remains the only option for the patients developing LF and in the event of HCC. Neonatal screening programs utilizing blood succinyl acetone as the marker should be encouraged especially in the countries, such as Turkey, with high prevalence of consanguineous marriages.

Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey.

BACKGROUND/AIMS: A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations. MATERIALS AND METHODS: The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart. RESULTS: In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas. CONCLUSION: After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.

Inflammatory bowel disease in Turkish children.

BACKGROUND: This study was undertaken to evaluate demographics, clinical manifestations, laboratory findings and outcomes of children with inflammatory bowel disease (IBD) in Turkey. METHODS: We analyzed the medical records of 127 children diagnosed with IBD (under 18 years old) between January 2004 and January 2012 in 8 pediatric gastroenterology centers. RESULTS: Of the 127 patients, 90 (70.9%) suffered from ulcerative colitis (UC), 29 (22.8%) from Crohn's disease (CD), and 8 (6.3%) from IBD unclassified. The mean age of the 127 patients was 11.6 ± 4.1 years, and 11.8% of the patients were below 5 years old. Of the patients, 49.6% were male, and males were more predominant in patients with CD than in those with UC (72.4% vs. 42.2%, P = 0.008; a male/female ratio of 2.62 in CD, P = 0.0016). Approximately one fifth of the patients had extra-intestinal manifestations and 13.3% of the patients had associated diseases. Extraintestinal manifestations and associated diseases were more common in early onset disease [P = 0.017, odds ratio (OR) = 4.02; P = 0.03, OR = 4.1]. Of the patients, 15% had normal laboratory parameters including anemia, high platelet count, hypoalbuminemia, hypoferritinemia, and high sedimentation rate. Area under receiver operation characteristics was used to predict pancolitis in patients with UC. The values of C-reactive protein, sedimentation rate and pediatric ulcerative colitis activity were 0.61 (P = 0.06), 0.66 (P = 0.01) and 0.76 (P = 0.0001), respectively. Four (4.4%) patients with UC underwent colectomy, and finally two (1.5%, 95% confidence interval: 0-3.7%) patients died from primary disease or complications. CONCLUSIONS: IBD is an increasing clinical entity in Turkey. Features of IBD are similar to those in other populations, but prospective multicenter studies are needed to analyze the true incidence of IBD in Turkish children.

Two novel UBR1 gene mutations in a patient with Johanson Blizzard Syndrome: A mild phenotype without mental retardation.

Johanson-Blizzard Syndrome (JBS) (MIM #243800) is a rare autosomal recessive genetic disorder characterized by exocrine pancreatic insufficiency, abnormal facial appearance and varying degrees of mental retardation. Mutations in UBR1 gene (MIM *605981) are considered to be responsible for the syndrome. Here, we report a 3 year-old mentally normal JBS girl. The patient presented with exocrine pancreatic insufficiency as well as failure-to-thrive. On dysmorphological examination, she was noted to have an abnormal hair pattern with frontal upsweep and alae nasi hypoplasia. With these findings, JBS diagnosis was established clinically. Molecular analysis of the UBR1 gene revealed two inherited novel mutations; one coming from each parent. These novel mutations were c. 1280T>G and c. 2432+5G>C, and they were found to be disease causing via in-silico analysis. In conclusion, for patients with longstanding exocrine pancreatic insufficiency, it should be considered as being symptomatic of a far broader picture. To omit connection with rare genetic diseases, such as Johanson-Blizzard Syndrome, a detailed dysmorphological examination ought to be performed.

Application of endoscopic hemoclips for nonvariceal upper gastrointestinal bleeding in children.

BACKGROUND/AIMS: Data about the efficiency and outcome of therapeutic endoscopic techniques in children with nonvariceal upper gastrointestinal bleeding (UGB) are scarce. We aimed to analyze our experience with endoscopic hemoclip application in children with non-variceal UGB. MATERIALS AND METHODS: During a 3-year period, a total of 1715 endoscopies were performed in our pediatric endoscopy unit; 182 (10.6%) of them were performed for UGB to 158 patients. Fifty-six of them had emergent endoscopy. Among them, 15 cases with nonvariceal UGB were only given endoscopic hemoclips. Demographic, clinical, and laboratory findings at initial admission; endoscopic appearance of bleeding lesions; and outcome of hemoclip application were recorded from the hospital files and endoscopy records. RESULTS: Ten patients (66.6%) had gastric ulcer, 3 (20%) had duodenal ulcer, 1 (6.7%) had Dieulafoy lesion, and 1 (6.7%) had bleeding at the post-polypectomy site. Initial homeostasis after hemoclip application was achieved in all patients (100%). Rebleeding was seen in only one patient (6.5%) with a Dieulafoy lesion, who needed hemoclip application for a second time, and the bleeding was controlled successfully. Permanent hemostasis was 100%. The median number of hemoclips used per case and per application was 3.4 and 3.2, respectively. None of the patients experienced any complication related to hemoclip application. Median duration of hospitalization was 6 days. On follow-up, none of the patients received surgical therapy, and 30-d mortality related to bleeding was 0%. CONCLUSION: The use of hemoclips for nonvariceal UGB in children is an effective modality to control bleeding without any complications in children.

The association of Alagille syndrome and craniosynostosis.

Alagille syndrome is associated with various ocular abnormalities, including pseudopapilledema or optic disk edema due to increased intracranial pressure. Several mechanisms have been proposed to explain the mechanism of intracranial hypertension in Alagille syndrome. Craniosynostosis is an unusual but significant cause of increased intracranial hypertension in Alagille syndrome. It has recently been demonstrated in animal models that Jagged1 gene in which mutations are responsible for Alagille syndrome may also take part in cranial suture formation. We report a child with Alagille syndrome and craniosynostosis who presented with pruritus, elevated liver enzymes, and suspected increased intracranial pressure.

Late-onset graft-versus-host disease after pediatric living-related liver transplantation for Langerhans cell histiocytosis.

GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching.

Evaluation of growth after liver transplantation in Turkish children.

AIMS: Currently, the main interest in childhood liver transplantation (LT) is to prevent long-term complications and optimize growth. The aim of this study is to analyze (1) nutritional status in the pretransplantation period, and (2) posttransplantation growth and associated factors in children. PATIENTS AND METHODS: Eighty children were included in the study. Height (Z (H)) and weight (Z (W)) Z scores were calculated before transplantation and postoperatively at the 6th month and 1st, 2nd, 3rd, 4th, and 5th year. RESULTS: Patients' Z (H) and Z (W) scores at LT were -1.6 ± 1.3 and -1.5 ± 1.4, respectively. Both Z (H) and Z (W) scores increased after LT, especially in the first 6 months, and then continued to rise gradually. Both reached beyond -1 Z score at 2nd year and -0.5 at 4th year. Age, primary diagnosis, total steroid dose (<1,000 mg), and absence of rejection episodes had positive impact on posttransplantation growth, whereas gender, immunosuppression type, surgical complications, and presence of tumor had no impact on posttransplantation growth. Age at time of LT was negatively correlated with Z (W) score at 5th year (P = 0.02, r = -0.43). Both Z (W) and Z (H) scores at time of LT were positively correlated with Z (W) and Z (H) scores and negatively correlated with ∆Z (W) and ∆Z (H) scores at 5th year. CONCLUSIONS: LT is not only a modern, life-saving treatment technique but also an efficient method of facilitating growth, an indispensable component of childhood and the best indicator of health.

Infectious complications in pediatric liver transplantation candidates.

We analyzed infections that occurred within one month prior to LT, identified factors associated with their occurrence and effect of infections on post-transplant mortality. The study group included 40 consecutive children who underwent LT. Sites and types of infection and culture results were recorded prospectively. IID was assessed. Risk factors for the infectious events were analyzed. Forty infection episodes were found in 24 patients (60%); 90% were bacterial, 7.5% fungal, and 2.5% viral. Overall, IID was 38.2 per 1000 patient days. Sites of bacterial infection were urinary tract in 13 events (36.1%) and blood stream in 11 events (30.5%). Bacteremia (culture positive infection episodes) was identified in 19 events (52.7%). Gram-negative isolates were twice as frequent as Gram-positive infections (63.1% vs. 36.9%). Risk factors for the infectious complications were young age, low body weight, prior abdominal surgery, chronic liver disease related to biliary problems, presence of ascites, portal hypertension and cirrhosis, and high PELD score (p < 0.05 for all). Infectious complications in pediatric LT candidates are common. Preventive measures are important not only to reduce the infectious complications but also to prevent the post-operative mortality.

Foreign body ingestion in Turkish children.

Foreign body ingestion (FBI) is a common problem in the pediatric population. Even though morbidity and mortality due to foreign body ingestion are rare in childhood, they may cause serious anxiety in parents. We aimed to analyze the clinical presentation, etiology and management strategy of FBI in children in our country. Records of children admitting with a history of FBI over a three-year period were reviewed retrospectively. Data regarding gender, age, type of the ingested body, management strategy and outcome of the patients were recorded. Of 176 children, 98 (55.6%) were male. Mean age +/- SD of the patients was 3.75 +/- 4.25 years, and most of the patients were below four years of age (71.5%). Most of the children (64.7%) were seen within 48 hours, and most were asymptomatic. Blue beads attached to a safety pin (a cultural good luck charm) (38.6%), coins (27.8%) and turban pins (18.1%) were the most commonly observed foreign bodies. The blue beads/safety pin were found to be ingested primarily by infants, while ingestion of turban pins was mostly seen in adolescent girls who covered their heads. Localization of the foreign bodies was in the distal small intestine, stomach and esophagus in 61.4%, 23.8% and 14.7% of the cases, respectively. Sixty-nine endoscopic interventions were performed in 61 patients (34.6%), and these accounted for 7.3% of all endoscopic interventions during the three-year period. No major complication was observed during the procedure, and none of the patients underwent surgery. The frequently used accessory devices were retrieval net basket (57.9%), snare for pins (17.3%), tripod forceps and rat-tooth forceps. The blue beads/safety pin and turban pin were the commonly ingested foreign bodies in our center due to cultural factors. Education of the parents and of adolescent girls should greatly reduce the incidence of FBI. Endoscopic removal is safe without any major complications.

Successful treatment of a child having generalized Kaposi's sarcoma after living donor liver transplantation with conversion to sirolimus.

SRL is a new and potent immunosuppressive agent that has been successfully introduced in organ transplantation. In contrast to other immunosuppressive agents, SRL has a potent antitumor activity both in vitro and in vivo. Herein, we report a child with Kaposi's sarcoma that was diagnosed 30 months after LDLT and treated successfully with only conversion to SRL monotherapy. KS regressed completely at the end of the first month and remained in remission during 28 months follow-up.

Helicobacter pylori infection in children with celiac disease.

OBJECTIVE: To analyze the prevalence of Helicobacter pylori (H. pylori) infection in children with celiac disease (CD) and to examine the role of H. pylori infection in clinical, laboratory and histopathological presentations of CD. MATERIAL AND METHODS: Data on 96 children with CD and 235 children who underwent endoscopy were compared for the prevalence and gastric histology pattern of H. pylori. Clinical presentation, laboratory and histological findings of CD children with and without H. pylori infection were compared. RESULTS: Twenty-one subjects (21.8%) in the CD group and 56 subjects (23.8%) in the control group had H. pylori gastritis. Gastric metaplasia is higher in CD patients with H. pylori gastritis (19%) than in patients without H. pylori gastritis (1.3%) and in the control group (3.5%) (p<0.05 for all groups). Abdominal distension is more common at initial admission in CD patients with H. pylori gastritis (57.1% versus 14.6%, p<0.05). No significant difference was found between H. pylori (+) and (-) CD patients in terms of prevalence of anemia, iron deficiency and iron-deficiency anemia. Only mild duodenal histological findings were more common in H. pylori patients (57.1% versus 26.7%, p<0.05). CONCLUSIONS: CD may be associated with H. pylori gastritis, but it does not affect the clinical presentation of the disease, except for abdominal distension; CD is associated with mild duodenal lesions. A gluten-free diet improves the symptoms in all patients independently of the presence of H. pylori gastritis. Gastric metaplasia increases in the presence of H. pylori gastritis. Further prospective studies are needed to examine the clinical and histopathological outcomes of gastric metaplasia associated with H. pylori gastritis in CD patients.

Association of mast cells and liver allograft rejection.

MCs are important effector cells in a broad range of immune responses. Their role in liver allograft rejection is not clear. Twenty-one liver transplant recipients (mean age +/- s.d.; 10.2 +/- 4.1 yr) who experienced a rejection episode are included in this study. Biopsy specimens from normal livers (allograft biopsy with normal histopathology n = 5 and naive livers n = 6), transplanted livers with CR (n = 5), and transplanted livers with ACR (n = 26) were studied. The total number of PT in each biopsy specimen was documented, and the number of PT that contained MCs was expressed as a percentage of the total number of PT. MCs, percentage of PT containing MCs and the average number of MCs/PT was significantly higher in rejection specimens than in control biopsy samples. All parameters were significantly higher in CR group than AR groups. Increasing grades of rejection was also associated with progressively more MCs and MC/PT (r = 0.68 p = 0.000; r = 0.58 p = 0.002). Only serum bilirubin level was related to the MCs in AR group. Only MC/PT was detected as an independent predictor of graft survival (p = 0.011, RR 2.87 95% CI 1.3-6.5). Despite the fact that the role of MCs in liver allograft rejection is still unknown; they exist in inflammatory infiltrates during pediatric liver allograft rejection. MC-rich portal infiltrates may distinguish chronic liver rejection from other inflammatory states such as AR, hepatitis and biliary obstruction.

Fatty liver due to high levels of serum tacrolimus after liver transplantation.

Tacrolimus has been used extensively for immunosuppressive therapy in pediatric liver transplant recipients. However, patients who are exposed to high levels of serum tacrolimus tend to be associated with a higher incidence of significant nephrotoxicity, neurotoxicity, pruritus, alopecia, diabetes and infection. We herein report a child who developed increased serum transaminase levels and liver steatosis as a result of raised trough blood level of tacrolimus (30 ng/ml for 3 days) in association with rotavirus gastroenteritis.

Liver transplantation for progressive familial intrahepatic cholestasis: clinical and histopathological findings, outcome and impact on growth.

In this study, we analyze the demographic features, clinical and histopathological findings in patients who underwent liver transplantation for progressive familial intrahepatic cholestasis. We also analyze outcome and impact of liver transplantation on growth and bone mineral content. Most of the patients were presented with jaundice mainly beginning within the first six months. At the time of initial admission; eight patients had short stature (height SD score<2), and four patients had weight SD score<2. Liver transplantation were performed at the age of 43.2+/-27 months (range 9 to 96 months), 6.5+/-3.5 months later after the first admission. Infection, surgical complications and osmotic diarrhea associated with severe metabolic acidosis were noted in 41.4%, 16.6% and 33.3%, respectively. One patient developed posttransplant lymphoproliferative disorder. Overall; 1 year graft and patient survival was 69.2% and 75%, respectively. At the end of the 1st year only 2 patients had height SD score<2. Linear regression of height gain against increase in total body BMD measured at the time of transplantation and 1 year after liver transplantation gave a coefficient r=0.588 (p=0.074). No correlation was found between the height gain and age and PELD score at time of transplantation, and no difference was noted between the sexes and donor type. Liver transplantation is effective treatment modality with good outcome and little morbidity, and increases the growth acceleration in patients with PFIC associated with cirrhosis.

Morphometric analysis of small-bowel mucosa in Turkish children with celiac disease and relationship with the clinical presentation and laboratory findings.

We aimed to analyze morphometric features of the small-bowel mucosa in children with celiac disease, to assess the diagnostic limit values of morphometric findings, and to examine the association of morphometric findings with the clinical presentation and laboratory findings. The study comprised 33 patients with celiac disease and 35 pediatric patients undergoing endoscopy for other causes. Biopsy specimens were reanalyzed for (1) intraepithelial lymphocytes, (2) goblet cells, (3) villous height, and (4) villous/crypt ratio. The morphometric parameters of the patients were compared with controls. Then celiac patients were divided into two groups according to the presence of total villous atrophy and clinical and laboratory findings were compared. Histologic examination revealed that goblet cells, villus height, and villous/crypt ratio were significantly lower and intraepithelial lymphocytes were significantly higher in celiac patients. Cutoff values for intraepithelial lymphocytes and goblet cells in celiac patients were 31/100 and 7.8/100 epithelial cells, respectively. Moreover, for villus height and villous/crypt ratio, cutoff values were 633 microm and 0.72, respectively. Serum folic acid and vitamin B(12) levels were significantly lower in patients with total villous atrophy and were positively correlated with the severity of villous atrophy. We suggest that morphologic examination and laboratory data are important for definitive diagnosis. Villous/crypt ratio is the most sensitive and specific parameter, and intraepithelial lymphocytes may be used along with villous/crypt ratio, especially in the early phase. Folic acid and vitamin B(12) levels are good indicators of villous atrophy.