Histological healing after infliximab induction therapy in children with ulcerative colitis

AIM: To verify the impact of induction therapy with infliximab(IFX) on mucosal healing in children with ulcerative colitis(UC).METHODS: The study included all UC pediatric patients treated with IFX at our center over the last10 years. The data were collected from patients' medical charts and analyzed retrospectively. A total of 16 patients with UC underwent colonoscopy with sample collection before and after three IFX injections.Pediatric Ulcerative Colitis Activity Index(PUCAI)was used to assess the clinical condition; endoscopic features were classified according to the Baron scale;and histological changes were evaluated according to the protocol of The British Society of Gastroenterology and Geboes Index. Clinical response was defined as a ≥ 20-point reduction in PUCAI index, and clinical remission as PUCAI index < 10 points. Endoscopic mucosal remission was defined as completely normal(score 0) on the Baron scale. Histological remission was defined as grade 0 in the Geboes Index. To assess correlation between variables, Spearman's rank correlation coefficient was used.RESULTS: Clinical remission(PUCAI < 10) at week 8 was achieved in 68.75% of investigated subjects. Endoscopic mucosal remission at week 8(Baron 0) was observed in 12.5% of patients. Histological remission(Geboes 0)after induction therapy with IFX was noticed in 18.75%cases. A general histological improvement, expressedby normal surface and crypt architecture, number of crypts, and lamina propria cellularity, was observed in six(37.5%) patients; there was no improvement in nine(56.25%) individuals, and worsening was observed in one(3.75%) case. Changes were not related to UC location. A reduction of inflammatory process was observed in 10(62.5%) patients; there were no changes in four(25%) individuals, and the inflammation became more severe in two(12.5 %) cases. Simultaneous clinical, endoscopic and histological improvement of parameters assessing disease activity at week 8 was noticed in six(37.5%) patients. 55.5% of investigated patients with normal mucosa seen on endoscopy showed no inflammation on histology. A Baron score of 2 and 3showed a good correlation with histology results(78.2%of patients with a Geboes Index ≥ 3).CONCLUSION: IFX has a positive histological effect in more than one-third of UC patients. IFX reduces intestinal inflammation and improves clinical condition.

Composition of inflammatory infiltrate and its correlation with HBV/HCV antigen expression

瞄准：学习肝的作文煽动性在从长期地感染亲肝病毒并且到的病人的活体检视材料渗入评估关联煽动性与肝炎 B (HBV ) 和丙肝病毒(HCV ) 渗入在长期的 B 和 C 肝炎的病毒的抗原表示。方法：煽动性的房间的显型被 EnVision 系统评估，用单音的同种细胞的抗体的一块面板。HBV 和 HCV 抗原分别地与单音的同种细胞的 anti-HBs， polyclonal anti-HBc 和 anti-HCV 抗体的使用被检测。结果：肝的细胞的作文煽动性渗入在有 B 和 C 肝炎的病人是类似的：房间的 ~50%-60% 是 T 助手淋巴细胞。约 25% 是 T 细胞毒素的淋巴细胞；B 淋巴细胞包括了中的 15% 个煽动性渗入；包括 NK，另外的房间总计了 10% 。HLA 抗原 paralleled 的表示煽动性的活动。门 lymphadenoplasia 比在肝炎 B (30.6%) 在丙肝(54.5%) 更经常被发现。HBcAg 的表示在中等或严重的活动的长期的 B 肝炎更经常被发现。在感染 HBV 的情况中的全面煽动性的活动没在 hepatocytes 与 HBsAg 表示的紧张相关。煽动性渗透伴随了 HCV 抗原的焦点的表示。在抗原表示和炎性反应原位之间的直接关联比 B 在丙肝更经常被注意。结论：不管肝炎的病原学和活动，部件煽动性在肝渗入是类似的。全面煽动性的活动没与 HBsAg 和 HCVAg 的表示相关；然而， HBcAg 表示伴随了中等、严重的活动的长期的肝炎 B。

Progressive familial intrahepatic cholestasis—farnesoid X receptor deficiency due to NR1H4 mutation:A case report

BACKGROUND Functioning farnesoid X receptor(FXR;encoded by NR1H4)is key to normal bile acid homeostasis.Biallelic mutations in NR1H4 are reported in a few children with intrahepatic cholestasis.We describe a boy with progressive familial intrahepatic cholestasis and homozygous mutation in NR1H4.CASE SUMMARY A boy had severe neonatal cholestasis with moderate hypercholanemia and persistently elevated alpha-fetoprotein.Despite medical treatment,coagulopathy was uncontrollable,prompting liver transplantation at age 8 mo with incidental splenectomy.The patient experienced catch-up growth with good liver function and did not develop allograft steatosis.However,1 year after transplant,he died from an acute infection,considered secondary to immunosuppression and asplenia.A homozygous protein-truncating mutation,c.547C>T,p.(Arg183Ter),was subsequently identified in NR1H4,and both parents were shown to be heterozygous carriers.Absence of FXR and of bile salt export pump expression was confirmed by immunostaining of explanted liver.CONCLUSION Severe cholestasis with persistently high alpha-fetoprotein and modest elevation of serum bile acid levels may suggest FXR deficiency.Some patients with FXR deficiency may not develop allograft steatosis and may respond well to liver transplantation.

Inter-observer variability in histopathological assessment of liver biopsies taken in a pediatric open label therapeutic program for chronic HBV infection treatment

瞄准：到我们的知识，在感染 HBV 的孩子的肝活体检视调查结果的内部观察员的可变性没迄今为止被学习。因此，我们试图比较不同病理学家对在在干扰素处理以前从孩子获得的肝活体检视分级和阶段的评价。方法：我们从 11 个医学中心收集了 920 活体检视。活体检视被 6 独立地考察估计了 Batts-Ludwig 的从学术中心的病理学家为分级和阶段得分。在观察员之中的令人满意的同意被定义为有一样的意见的至少 60% 观察员。在为一样的活体检视标本的最大、最小的分数之间的令人满意的分散被定义为 1 削尖的最大值。结果：为分级的令人满意的内部观察员的同意在 75.7% 活体检视在 51.6% 并且为阶段被获得。为分级分数的令人满意的分散在 72.7% 盒子中在 44.5% 并且为阶段被观察。结论：我们的学习表明那：(1 ) 病理学家们在他们对分级和肝活体检视的阶段的评价不同；(2 ) 为阶段的内部观察员的可变性为分级是比那低的；并且(3 ) 不管评价的内部观察员的可变性，有长期的 HBV 感染的孩子的多数对中等发炎温和、对中等纤维变性温和。

Clinical utility of quantitative multi-antibody Polycheck immunoassays in the diagnosis of coeliac disease

AIM:To evaluate the clinical utility of multi-antibody strategies in the diagnosis of coeliac disease(CD),the new quantitative Polycheck immunoassays were analysed.METHODS:Polycheck Celiac Panels(PCPs)are immunoenzyme screening assays for the quantitative measurement of coeliac-specific immunoglobulin class G(Ig G)or class A(Ig A)in serum.Lines of relevant antigens are coated together with five Ig G or Ig A standard lines used for the standard curve as positive control.PCP IgA consists of human recombinant human tissue transglutaminase(t TG)and deamidated gliadin peptides(DGP)as targets to detect Ig A antibodies.PCP IgG consists of t TG,DGP and IF(intrinsic factor)antigens to detect antibodies in Ig G class.PCPs were performed on 50 CD patients,including 6 cases with selective Ig A deficiency,and 50 non-coeliac controls.CD diagnosis was performed according to the ESPGHAN recommendations:The presence of specific anti-t TG-Ig A or anti-DGP-Ig G(in the case of Ig A deficiency)antibodies,typical histopathological changes in duodenal mucosa described in Marsh-Oberhüber classification as at least grade 2.The diagnosis of the majority of the control subjects was functional gastrointestinal disorders.The PCP results were compared with reference EliA Celikey.RESULTS:The usage of PCPs led to the correct identification of all CD patients.In our study,PCPs showed 100%agreement with the histopathological results.PCP IgA test showed a 98%concordance and correlated positively(R=0.651,P=0.0014)with Eli A Celikey test.The highest specificity and positive predictive value(both 100%)were observed for the detection of Polycheck anti-t TG-Ig A antibodies.The highest sensitivity and negative predictive value(both 100%)were achieved by Polycheck anti-DGPIg G antibody detection.The best performance(98%sensitivity and negative predictive value,100%specificity and positive predictive value,diagnostic accuracy-AU ROC 99%)was observed for the strategy of using both PCP IgA and IgG and determining positive outcomes of the test with two or more coeliac-specific antibodies detected.The majority of coeliac patients had multiple antibodies.All four antibodies were detected in 7(14%)cases,19 children(38%)were positive for three antibodies and 23(46%)were positive for two antibodies.CONCLUSION:The present study showed that detection of coeliac-specific antibodies with multi-antibody PCPs is effective and efficacious in the diagnosis of CD.