Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

Unusual presentation of cat scratch disease: case report.

Cat scratch disease (CSD) is an infection caused by Bartonella henselae, presents with non-specific symptoms like lymphadenopathy, fever, and fatigue. It can progress to disseminated disease, leading to complications such as liver and splenic micro abscesses, osteomyelitis, encephalitis, and uveitis. Diagnosis is challenging due to varied presentations and limited tests. Treatment involves supportive care, with severe cases requiring antimicrobial therapy. In this report, we present a case of Cat scratch disease characterized by an atypical clinical manifestation, hepatosplenic and paravertebral involvement.

Prognostic significance of metastatic lymph node ratio in gastric cancer: a Western-center analysis.

BACKGROUND: Tumor-node-metastasis (TNM) staging is the central gastric cancer (GC) staging system, but it has some disadvantages. However, the lymph node ratio (LNR) can be used regardless of the type of lymphadenectomy and is considered an important prognostic factor. This study aimed to evaluate the relationship between LNR and survival in patients who underwent curative GC surgery. METHODS: All patients who underwent radical gastric surgery between January 2014 and June 2022 were retrospectively evaluated. Clinicopathological features of tumors, TNM stage, and survival rates were analyzed. LNR was defined as the ratio between metastatic lymph nodes and total lymph nodes removed. The LNR groups were classified as follows: LNR0 = 0, 0.01 < LNR1 ≤ 0.1, 0.1 < LNR2 ≤ 0.25 and LNR3 > 0.25. Tumor characteristics and overall survival (OS) of the patients were compared between LNR groups. RESULTS: After exclusion, 333 patients were analyzed. The mean age was 62 ± 14 years. According to the LNR classification, no difference was found between groups regarding age and sex. However, TNM stage III disease was significantly more common in LNR3 patients. Most patients (43.2%, n = 144) were in the LNR3 group. In terms of tumor characteristics (lymphatic, vascular, and perineural invasion), the LNR3 group had significantly poorer prognostic factors. The Cox regression model defined LNR3, TNM stage II-III disease, and advanced age as independent risk factors for survival. Patients with LNR3 demonstrated the lowest 5-year OS rate (35.7%) (estimated mean survival was 30 ± 1.9 months) compared to LNR 0-1-2. CONCLUSION: Our study showed that a high LNR was significantly associated with poor OS in patients who underwent curative gastrectomy. LNR can be used as an independent prognostic predictor in GC patients.

Low Titer Tissue Transglutaminase Antibodies: A Link to Helicobacter pylori Infection?

INTRODUCTION: Low serum titer of anti-tissue transglutaminase (tTG) has been described in various conditions without any evidence of celiac disease (CD). Infectious agents have been suggested to trigger autoimmunity and promote the production of anti-tTG. The aim of this study was to investigate if there is a link between a positive celiac serology and concomitant Helicobacter pylori infection in children. METHODS: The data of 178 pediatric patients who underwent upper gastrointestinal endoscopy due to positive celiac serology were compiled. The patients whose histopathologic findings were not consistent with CD were followed on gluten-containing diet. The changes in the serum level of anti-tTG IgA on the follow-up were compared between H. pylori-infected and noninfected patients after the eradication of H. pylori. RESULTS: Of 155 patients who met the inclusion criteria, 119 (group 1) were diagnosed as CD, and duodenal histopathology of the remaining 36 children (group 2) was not compatible with CD. In group 2, 11 out of 36 (30.5%) patients were infected with H. pylori. After the eradication of H. pylori, anti-tTG IgA level either decreased or dropped below cutoff value in 9/11 (81%) patients while it was 20% in those who were not infected with H. pylori in the 6th month of the follow-up (p = 0.001). CONCLUSION: Our results suggest that H. pylori infection may be the cause of false or transient positive celiac serology. Thus, a positive celiac serology should be carefully interpreted in the presence of H. pylori infection before confirming the diagnosis of this life-long disease.

Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology.

Recent guidelines suggest non-biopsy serology-based approach for the diagnosis of celiac disease; however, there is no evidence-based data regarding noninvasive follow-up of mucosal healing. The aim of this study is to investigate the efficacy of serology in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. This is a validation study conducted at a university hospital. Patients who had biopsy proven celiac disease (Marsh III) at diagnosis, and had been followed-up for at least 12 months, were prospectively evaluated with duodenal biopsies. tTG-IgA and EMA tests were performed on the day of endoscopy. One hundred four patients with a mean age of 7.4 ± 4.02 years were included in the study. The sensitivity and specificity of tTG-IgA were 85.2% and 61% respectively, with a high negative predictive value (NPV) of 92.2% but a very low positive predictive value (PPV) of 43.4%. We found that a cutoff value of 68.5 U/mL for tTG-IgA had a sensitivity, specificity of 85.2% and 85.7% respectively. The AUC was 0.891. The sensitivity and specificity of EMA was 77.8% and 87% respectively, with a high NPV of 91.8% but low PPV of 67.7%. CONCLUSION: This study suggests that negative tTG-IgA and/or EMA can be used as an indicator of mucosal improvement in the follow-up of pediatric patients with celiac disease. However, positive serology (i.e., < 10 × ULN) may be misleading in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. WHAT IS KNOWN: • The tissue transglutaminase IgA (tTG-IgA) and endomysium IgA (EMA) tests are widely used, sensitive and reliable diagnostic tests, but their role in monitoring adherence to dietary treatment in celiac patients has not yet been demonstrated. • There is still no reliable and non-invasive marker of persistent villous atrophy or mucosal recovery. WHAT IS NEW: • Negative celiac serology detected in the follow-up of pediatric patients with celiac disease was successful in demonstrating histopathological mucosal healing. • Positive celiac serology, which is highly reliable in the diagnosis of celiac disease, has not been successful in reflecting mucosal status when used in the follow-up of pediatric patients with celiac disease.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Gastrointestinal Manifestations in Children with Primary Immunodeficiencies: Single Center: 12 Years Experience.

BACKGROUND: It has been reported that 5-50% of patients with primary immune deficiencies (PID) may present with or develop gastrointestinal (GI) manifestations. OBJECTIVE: This study was aimed at analyzing GI and related endoscopic, histopathological findings in children with PID. METHODS: Children with PID who were evaluated by endoscopy between 2005 and 2016 were enrolled in this study. Demographic data, growth parameters, signs and symptoms at diagnosis were obtained. RESULTS: Of 425 children with PID, 195 had GI manifestations. Forty-seven of 195 children required endoscopic investigation, 30 (63.8%) were male, and the mean age was 7.7 ± 5 years. The rate of consanguinity was 61.7%, and the most common symptom was chronic diarrhea (57.4%). Seventy-two percent of the patients were malnourished. Giardia intestinalis was detected in 4, and Helicobacter pylori was confirmed in 8/45 (17.7%) patients. Non-celiac villous flatting was discovered in 15.5% of patients. Twelve patients were diagnosed as having immunodeficiency associated inflammatory bowel disease (IBD)-like colitis. CONCLUSIONS: PID may present with GI manifestations or develop during the course of the disease. Investigating immunodeficiency in patients with atypical GI symptoms can provide an appropriate therapeutic option, and an improved quality of life, particularly in populations with a high rate of consanguinity.

Mesenchymal stem cells suppress hepatic fibrosis accompanied by expanded intrahepatic natural killer cells in rat fibrosis model.

Natural killer (NK) cells have antifibrotic effects. We have evaluated the influence of rat bone marrow-mesenchymal stem cell (BM-MSC) treatment on liver histology, biochemical liver function tests, systemic immunoregulatory state and NK cell distribution in liver and peripheral blood in rat model of common bile duct (CBD) ligation and compared the results with the control group. Rats were divided into three groups: (1) CBD ligated (CBDL) rats received phosphate-buffered saline (CBDL + PBS group) or (2) MSC (CBDL + MSC group) and sham-operated rats received MSC (healthy + MSC group). We found significantly decreased fibrosis scores with BM-MSC treatment in CBDL rats compared to the control (CBDL + PBS) group while no fibrosis developed in sham operated (healthy + MSC) group. BM-MSC treatment has decreased the inflammation as reflected by the significantly decreased T cell proliferation and inflammatory cytokine concentrations from splenocyte culture and liver tissue itself compared to CBDL + PBS. NK cells both in parenchyme and portal areas decreased significantly in liver and blood in CBDL + PBS compared to healthy + MSC while they were found to be increased in CBDL + MSC compared to CBDL + PBS rats. In conclusion, BM-MSCs may suppress hepatic fibrosis accompanied by expanded intrahepatic NK cells in CBDL rats. Thus, our animal study shows that MSC treatment holds great promise for treatment of patients with end-stage liver diseases through a possible mechanism by adopting the NK cell population and new studies investigating the role of NK cells and clinical fibrosis are warranted.Trial registration number: Marmara University Animal Care and Use Committee approval code: 73.2013.mar.

Appraising diagnostic performance of ELF test by pathological staging and digital quantification of liver fibrosis.

INTRODUCTION AND OBJECTIVES: A crucial issue when appraising the performance of non-invasive markers is the limitations of the reference standard they are compared to. Digital image analysis (DIA) was suggested as a reproducible approach expressing fibrosis numerically as a proportionate area (PA) (%). We aimed to evaluate ELF test with direct reference to PA (%), thereby explore the improvement in accuracy to discriminate significant fibrosis which may actually have been underestimated by categorical pathological staging. MATERIALS AND METHODS: PA (%) data were obtained by DIA of trichrome-stained liver biopsies of 52 chronic hepatitis patients. Paired serum samples of patients and additional 36 controls were performed to measure ELF test. Diagnostic performance characteristics of ELF test was derived in predicting significant fibrosis in the patient cohort, and also, in distinguishing healthy controls from patients with significant fibrosis. RESULTS: We found an AUROC value of 0.73 for ELF to predict significant fibrosis as assessed by DIA and a lower AUROC value of 0.66 when assessed by conventional pathology. Importantly, ELF test provided considerably high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis defined by Ishak F≥2 and TPA≥5% (AUROCs 0.93 and 0.94, respectively) with optimal ELF cut-off point of 8.4 for both. CONCLUSIONS: Digital quantification could represent a better reference standard than conventional pathology allowing a better discriminatory capability for ELF test. ELF test provided high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis suggesting a role as a screening strategy in the community setting.

Helicobacter pylori is undetectable in intraductal papillary mucinous neoplasm.

BACKGROUND: About half of the world population is infected with Helicobacter pylori (H. pylori), a bacterium associated with gastric cancer and considered to be a risk factor for pancreatic ductal adenocarcinoma. Whether the bacterium is associated with intraductal papillary mucinous neoplasm, believed to be a precursor of pancreatic ductal adenocarcinoma, is unknown. The aim of this study was to investigate the presence of H. pylori DNA in tissue sections of intraductal papillary mucinous neoplasm. METHODS: The presence of H. pylori DNA was tested in a retrospective controlled study of formalin-fixed, paraffin-embedded pancreatic tissues from 24 patients who underwent surgery for intraductal papillary mucinous neoplasm. Histologically normal tissues surrounding neoplasms were used as control. H. pylori DNA was evaluated after deparaffinization, DNA extraction, and purification, and results were evaluated statistically. RESULTS: Samples were collected from 13 males and 11 females with mean age 59 years (range 44-77), and consisted of 19 cases of main-duct and three cases of branched-duct intraductal papillary mucinous neoplasm. Two patients were diagnosed with pancreatic cancer and main-duct intraductal papillary mucinous neoplasm. H. pylori DNA was not detected either in intraductal papillary mucinous neoplasm tissue, or in surrounding normal tissue. CONCLUSIONS: Although H. pylori has been implicated in pancreatic ductal adenocarcinoma, it may not play a key role in the development of intraductal papillary mucinous neoplasm.

Nonalcoholic Fatty Liver Disease is Associated with Erectile Dysfunction: A Prospective Pilot Study.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Although the link between MetS and erectile dysfunction (ED) is well known, clinical studies investigating the association between NAFLD and ED are scant. AIM: To evaluate the relationship between NAFLD and ED. METHODS: Male patients with biopsy-proven NAFLD were prospectively asked to fill the five-item International Index of Erectile Function (IIEF-5) questionnaire. Their clinical and histologic variables were compared with the IEFF scores. MAIN OUTCOME MEASURES: IIEF scores; proportions of NAFLD patients who demonstrated ED and/or MetS; association between the severity of histological hepatic damage and ED. RESULTS: Forty male patients having an age range of 33 (24-57) and a mean age of 40.13 ± 10.22 years with biopsy-proven NAFLD had a median IIEF-5 score of 16 (9-25) and MetS was present in 23 (57.5%). ED severity distributions as moderate, mild, and no ED were 11 (27.5%), 16 (40%), and 13 (32.5 %), respectively. Histological NAFLD score was significantly higher in patients having ED compared with patients with no ED (5.63 ± 1.39 vs. 4.15 ± 1.46; P = .006). MetS diagnosis was significantly more common in patients having ED, compared with those without ED [19 (70.4%) vs. 4 (30.8%), respectively, P = .018)]. When patients with and without ED were compared, gamma glutamyl transferase was significantly lower in ED, whereas components of MetS did not correlate with ED. After multivariate analysis, NAFLD score has remained the only significant outcome associated with ED [P = .03; OR (95% CI): 2.38 (1.079-5.238)]. CONCLUSION: The current clinical study demonstrates a significant association between nonalcoholic steatohepatitis and ED for the first time. Our findings suggest liver damage may play role in the pathogenesis of ED in patients with NAFLD. Future studies are needed to expand the underlying common mechanisms responsible for this novel hypothesis.

Preoperative chemoradiation therapy decreases the number of lymph nodes resected during esophagectomy.

BACKGROUND: This study aimed to analyze the effect of preoperative chemoradiation on the adequacy of lymph node dissection. METHODS: Patients with esophageal cancer treated with esophagectomy by the same surgeon between 2004 and 2011 were reviewed. Specimens were examined by the same pathologist. Patients were grouped into two depending on the type of treatment received. RESULTS: Forty-seven patients with curative esophagectomy were included in the study. Twenty patients had preoperative chemoradiation followed by surgery and 27 had surgery alone. Open and hybrid esophagectomy approaches were used. The average number of lymph nodes dissected was 16 ± 10 (1-39). There was a significant decrease in the number of lymph nodes examined in patients with preoperative chemoradiotherapy in comparison to surgery alone (p = 0.001). Median length of stay was 12 days. R0 resection rate was 96%. The median survival was 36.3 months, with a 42% 5-year survival. Seven patients (25%) had complete pathologic response following chemoradiation. No significant difference was recorded in terms of disease recurrence (p = 0.3). While morbidity was higher in the preoperative therapy group with 30 day mortality of 10%, type of surgical approach does not seem to influence the number of lymph nodes dissected (p = 0.7). CONCLUSIONS: Preoperative chemoradiation decreases the number of harvested lymph nodes following esophagectomy regardless of the surgical technique used. The optimum number of lymph nodes currently recommended to be dissected for accurate nodal staging and survival needs revision in this group of patients.

Is perineural invasion (PN) a determinant of disease free survival in early stage colorectal cancer?

BACKGROUND/AIMS: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy. METHODOLOGY: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect. CONCLUSIONS: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters.

OBJECTIVE: Human epidermal growth factor-2 (HER-2) overexpression has prognostic value in breast cancer. However, the significance of HER-2 positivity in gastric cancer is controversial. In this study, we investigated the frequency of overexpression of HER-2 and its relationship with clinicopathological findings and impact on survival in gastric cancer. MATERIAL AND METHODS: Gastric cancer patients, operated in Marmara University Faculty of Medicine, Pendik Training and Research Hospital, General Surgery Department, between January 2012-December 2013 were enrolled in this study. Medical records were retrospectively evaluated. Tissue samples were stained by immunohistochemistry (IHC) method, and were followed by fluorescence in situ hybridization (FISH) in those with positive results. HER-2 expression rates and its association with other histopathological features and survival have been analyzed. RESULTS: 135 patients were enrolled in the study, with 88 (65%) male and 47 (35%) female patients. The median age was 61 (29-84) years. Only 11 patients (8%) were positive for HER-2. HER-2 positive patients were similar to negative patients in terms of age, gender, tumor size, tumor location, tumor T stage, lymph node metastasis, histological type, differentiation, lymphovascular invasion, perinodal, perineural invasion and stage. No significant difference was detected on 1 and 2-year overall and disease-free survival rates between receptor positive and negative groups. CONCLUSION: Consistent with the literature data, HER-2 positivity rate in this study was approximately 8%, but this positivity has not been found to be associated with either clinical and pathological parameters or overall and disease-free survival.

Detection of hepatic steatosis using the controlled attenuation parameter: a comparative study with liver biopsy.

OBJECTIVE: Measurements of controlled attenuation parameter (CAP) with transient elastography (FibroScan®; EcoSens SA, Paris, France) may provide an accurate noninvasive assessment of hepatic steatosis. Herein, we prospectively determined the accuracy of liver fat quantification with CAP values in patients with chronic liver diseases and compare the results with those of histological assessment of steatosis as reference standard. MATERIALS AND METHODS: We enrolled 50 Turkish patients with various forms of chronic liver diseases. All patients underwent both CAP assessment and ultrasonography-guided liver biopsy. RESULTS: On liver biopsy, 16 (32%) patients had S0, 12 (24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. The CAP values increased significantly (p<0.001) for each steatosis stage on liver biopsy: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m. A cutoff value of 257 dB/m could distinguish significant steatosis (S2-S3) from S0 (Sn 89%, Sp 83%, positive likelihood ratio 5.33, negative likelihood ratio 0.13, AUROC=0.93). Multivariable analysis indicated that neither liver fibrosis (p=0.58) nor disease etiology (p=0.96) had a significant impact on the association between CAP and the stage of steatosis. CONCLUSION: The determination of CAP using transient elastography can represent an important step forward toward the goal of an "imaging liver biopsy".

A comparison of FibroMeter™ NAFLD Score, NAFLD fibrosis score, and transient elastography as noninvasive diagnostic tools for hepatic fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND: Noninvasive markers that purport to distinguish patients with non-alcoholic fatty liver disease (NAFLD) with fibrosis from those without must be evaluated rigorously for their classification accuracy. Herein, we seek to compare the diagnostic performances of three different noninvasive methods (FibroMeter™ NAFLD score, NAFLD Fibrosis score (NFSA), and Transient Elastrography [TE]) for the detection of liver fibrosis in NAFLD patients. METHODS: A total of 88 patients with biopsy-proven NAFLD were included. The Kleiner system was used for grading fibrosis in liver biopsies. The FibroMeter™ NAFLD score was determined using a proprietary algorithm (regression score). The NFSA score was calculated based on age, hyperglycemia, body mass index, platelets, albumin and serum aminotransferase levels. TE was performed using the Fibroscan apparatus. RESULTS: The sensitivities/specificities for the FibroMeter™ NAFLD score, NFSA, and TE for the diagnosis of significant fibrosis (F2 + F3 + F4 fibrosis) were 38.6%/86.4%, 52.3%/88.6%, and 75.0%/93.2%, respectively. The areas under the receiver operating characteristic curves of TE were significantly higher than those of both the FibroMeter™ NAFLD score and NFSA. No significant differences were found between the FibroMeter™ NAFLD score and NFSA for the detection of significant and severe fibrosis, although the diagnostic performance of the FibroMeter™ NAFLD score was higher than that of the NFSA score for cirrhosis. CONCLUSIONS: In summary, TE showed the best diagnostic performance for the noninvasive assessment of liver fibrosis in NAFLD patients. The diagnostic performances of the FibroMeter™ NAFLD score and NFSA did not differ significantly for the detection of both significant and severe fibrosis.

Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study.

Background and Aim: This study aimed to investigate the predictive value of various non-invasive scores for identifying the progression of hepatic fibrosis over time in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Materials and Methods: We examined 69 patients with NAFLD who had undergone two liver biopsies at an average interval of 21.3±9.7 months. Progression and regression of fibrosis were defined as an increase or decrease of at least one stage in fibrosis between the initial and follow-up biopsies, respectively. The Fibrosis-4 Index (FIB-4), NAFLD Fibrosis Score (NFS), Agile 3+, Agile 4, and FibroScan-AST (FAST) scores were calculated at the initial biopsy. Results: Comparison of paired biopsies revealed that 45% of participants (n=31) exhibited no change in fibrosis stages, 26% (n=18) experienced progression, and 29% (n=20) demonstrated regression. Multivariable logistic regression analysis identified the FAST score as the only independent predictor of progressive fibrosis, with the odds increasing by 19% (95% CI: 8-38%, p<0.05) for each unit increase in the FAST score at the initial biopsy. No independent predictors for fibrosis regression were identified. Conclusion: Higher baseline FAST scores were associated with an increased likelihood of fibrosis progression, independent of other variables. Thus, the FAST score could serve as both a diagnostic and prognostic tool for fibrosis in patients with NAFLD.

Prognostic significance of mucinous histology in left­sided metastatic colorectal cancers with wild­type RAS and evaluation of backbone chemotherapy regimens.

Mucinous colorectal adenocarcinoma (MCAC) is a distinct subtype of colorectal carcinoma (CRC). The prognostic and predictive significance of mucinous histology remains controversial. It was aimed to investigate the prognostic and/or predictive role of mucinous histology in left-sided metastatic CRC (mCRC) with wild-type RAS. This is a retrospective multicenter study of mCRC treated with first line anti-EGFR combined 5-fluorouracil based chemotherapy (CT). Patients were stratified according to presence (>50% extracellular mucin) or absence of mucinous histology. Survival analyses were performed firstly regardless of treatment options and then performed as separating according to CT regimens. Additional analyses were performed for MCAC patients considering backbone CT regimens. A total of 125 patients were included, consisting of 40 (32.0%) patients with MCAC and 85 (68.0%) patients with non-MCAC. Median follow-up time was 19.7 months. Median progression-free survival (PFS) was 10.7 months in all patients, and PFS was lower in MCAC than non-MCAC (9.9 vs. 12.0 months, respectively, P=0.005). Median overall survival (OS) was 25.7 months in all patients. OS was lower in MCAC than non-MCAC (22.8 vs. 29.7 months, respectively, P=0.005). When considering backbone CT regimens, in multivariate analyses, mucinous histology was an independent prognostic factor for OS in both for mFOLFOX6 (HR: 1.92, P=0.04) and FOLFIRI (HR: 2.04, P=0.04) groups and was associated with poor PFS in only mFOLFOX6 (HR: 3.86, P<0.001) group. When outcomes were analyzed for the MCAC group, median OS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 22.47 and 14.22 months, respectively (P=0.41). Median PFS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 10.15 and 8.11 months, respectively (P=0.73). The study revealed poor prognosis of mucinous histology, both in whole study population and in backbone CT groups. Moreover, lower PFS of MCAC patients was revealed in only mFOLFOX6 group and this finding may be a valuable issue for the future research. However, considering all analyses, the present results did not indicate a special benefit of any backbone CT regimen for MCAC patients.

Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.

Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.