The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

Comparison of four scoring systems for risk stratification of upper gastrointestinal bleeding.

OBJECTIVE: This study aimed to compare the performances of the Glasgow-Blatchford Bleeding Score (GBS), pre-endoscopic Rockall score (PRS), complete Rockall score (CRS), and Cedars-Sinai Medical Center Predictive Index (CSMCPI) in predicting clinical outcomes in patients with upper gastrointestinal bleeding (UGIB). METHODS: Patients who were admitted to the emergency department because of UGIB and underwent endoscopy within the first 24 hour were included in this study. The GBS, PRS, CRS, and CSMCPI were propectively calculated. The performances of these scores were assessed using a receiver operating characteristic curve. RESULTS: A total of 153 patients were included in this study. For the prediction of high-risk patients, area under the curve (AUC) was obtained for GBS (0.912), PRS (0.968), CRS (0.991), and CSMCPI (0.918). For the prediction of rebleeding, AUC was obtained for GBS (0.656), PRS (0.625), CRS (0.701), and CSMCPI (0.612). For the prediction of 30-day mortality, AUC was obtained for GBS (0.658), PRS (0.757), CRS (0.823), and CSMCPI (0.745). CONCLUSION: These results suggest that effectiveness of CRS is higher than that of other scores in predicting high-risk patients, rebleeding and 30-day mortality in patients with UGIB.

AST/ALT ratio is not useful in predicting the degree of fibrosis in chronic viral hepatitis patients.

BACKGROUND AND AIM: Noninvasive tests are primarily used for staging hepatic fibrosis in patients with chronic liver disease. In clinical practice, serum aminotransferase levels, coagulation parameters, and platelet count have been used to predict whether or not a patient has cirrhosis. In addition, several studies have evaluated the accuracy of combinations (or ratios) of these measures. The present study aimed to investigate the relationship between five noninvasive models [AST/ALT ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), age-platelet index (APind), and King's score] and the degree of hepatic fibrosis as determined by biopsy in patients with chronic hepatitis B and C. PATIENTS AND METHODS: A total of 380 patients with viral hepatitis (237 with chronic hepatitis B and 143 with chronic hepatitis C) who were seen at our clinic between January 2005 and January 2011 were retrospectively analyzed. The degree of fibrosis was determined using the Ishak score. Patients with a fibrosis score of 0-2 were considered to have low fibrosis and those with a score between 3 and 6 were considered to have high fibrosis. Five noninvasive models were compared between the groups with low and high fibrosis. RESULTS: There were statistically significant differences between the hepatitis B and C patients with high and low fibrosis with respect to APind (4.49±2.35 vs. 2.41±1.84; P<0.001 in hepatitis B and 4.83±2.25 vs. 2.92±1.88; P<0.001 in hepatitis C), APRI (1.00±1.17 vs. 0.47±0.39; P<0.001 in hepatitis B and 1.01±1.01 vs. 0.41±0.29; P<0.001 in hepatitis C), CDS (4.53±1.90 vs. 3.58±1.30; P<0.001 in hepatitis B and 4.71±2.03 vs. 3.42±1.49; P<0.05 in hepatitis C), and King's score (24.31±3.14 vs. 7.65±6.70; P<0.001 in hepatitis B and 24.82±2.55 vs. 8.33±7.29; P<0.001 in hepatitis C). There were no significant differences in the AAR between the hepatitis B and C patients with high and low fibrosis (0.78±0.31 vs. 0.74±0.34; P=0.082 in hepatitis B and 0.91±0.40 vs. 0.85±0.27; P=0.25 in hepatitis C). The area under the receiver-operating characteristic curve of the APind, APRI, CDS, and King's score in the hepatitis B group were 0.767, 0.710, 0.646, and 0.770, respectively; these values were 0.732, 0.763, 0.677, and 0.783, respectively, in the hepatitis C group. CONCLUSION: In conclusion, our data suggest that four of the five noninvasive methods evaluated in this study can be used to predict advanced fibrosis in patients with hepatitis B and C. However, there was no significant relationship between the degree of hepatic fibrosis and the AAR score, indicating that AAR is not useful in estimating the fibrosis stage in hepatitis B and C patients.

Adipo-R1 and adipo-R2 expression in colorectal adenomas and carcinomas.

BACKGROUND: Human adiponectin (ApN), a 30 kDa glycoprotein of 244-amino acids which is predominantly produced by adipocytes, exerts its effects via two receptors, namely adiponectin receptor-1 (adipo-R1) and adiponectin receptor-2 (adipo-R2) with differential binding affinity to globular adiponectin. Adiponectin receptor expression has been studied in several cancer tissues. However, there are no studies of colorectal adenomas which are considered to be precursors for colorectal carcinoma (CRC). OBJECTIVES: In the present study, the expression of adipo-R1 and adipo-R2 was investigated immunohistochemically in colorectal adenomas and colorectal carcinoma tissues in an attempt to determine associations with these tumors. MATERIALS AND METHODS: The study enrolled 50 CRC patients with tumor resection and 82 patients who were diagnosed with adenomatous polyps, classified as negative for neoplasia, low-grade dysplasia (L-GD) or high- grade dysplasia (H-GD). RESULTS: Expression of both adipo-R1 and adipo-R2 was found to be significantly lower in the CRCs than in colorectal adenomas (tubular and tubulovillous, p=0.009 and p<0.001, respectively). Adipo-R1 and adipo-R2 expression was also significantly lower in the CRC group when compared with the groups of patients with low grade dysplasia, high-grade dysplasia or no neoplasia (p=0.012 and p<0.001, respectively). In addition, it was observed that adipo-R2 expression was generally positive in the non-neoplastic group irrespective of the adipo-R2 expression. In the L-GD, H-GD and CRC groups, the adipo-R2 result was positive whenever adipo-R1 result was positive but some patients with negative adipo-R1 had positive adipo-R2 (p<0.001, p=0.004, p<0.001, respectively). CONCLUSIONS: This study indicated that ApN may play a role in the progression of colorectal adenomatous polyps to carcinoma through actions on adipo-R1 and adipo-R2 receptors.

Mean platelet volume is an important predictor of hepatitis C but not hepatitis B liver damage.

BACKGROUND: The mean platelet volume (MPV) is the most commonly used measure of platelet size and is a potential marker of platelet reactivity. In this study, we aimed to explore the relationship between hepatic histopathology in viral hepatitis and MPV levels, which are associated with platelet count and activity. MATERIALS AND METHODS: We performed a retrospective case-control study of baseline histological and clinical parameters in chronic hepatitis B and C patients in our tertiary reference center between January 2005 and January 2011. Two hundred and five chronic hepatitis B patients and 133 chronic hepatitis C patients who underwent liver biopsy were included in the study. The patients were divided into two groups: Chronic hepatitis B and chronic hepatitis C and were additionally divided into groups of two according to histological activity index (HAI) and fibrosis scores obtained by liver biopsy results (according to the Ishak scoring system). The clinical characteristics of chronic viral hepatitis patients, including demographics, laboratory (especially MPV), and liver biopsy findings, were reviewed. RESULTS: One hundred and forty-three patients were male (69.1%), and the mean age was 41.9 ± 12.75 with an age range of 18-71 years in hepatitis B patients. In the classification made according to HAI, 181 patients were in the low activity group (88.3%) and 24 in the high activity group (11.7%). In the evaluation made according to fibrosis score, 169 patients were found to have early fibrosis (82.4%) and 36 were found to have advanced fibrosis (17.6%). In patients with hepatitis B, there was no statistically significant difference in terms of their MPV values between the two groups, separated according to their degree of activity and fibrosis. Sixty-three patients were male (47.3%), and the mean age was 50.03 ± 12.75 with an age range of 19-75 years. In the classification made according to HAI, 109 patients were in low activity group (81.9%) and 24 in high activity group (18.1%). In the evaluation made according to fibrosis score, 101 patients were found to have early fibrosis (75.9%) and 32 have advanced fibrosis (24.1%). There was a statistically significant difference between the activity and fibrosis groups of the hepatitis C patients (P = 0.04 and P = 0.02, respectively). CONCLUSION: MPV values are more reliable in hepatitis C patients than hepatitis B for predicting the advanced damage in liver histology. This finding might be useful for the detection of early fibrosis and also starting early treatment, which is important in hepatitis C.

Association of adiponectin receptor (Adipo-R1/-R2) expression and colorectal cancer.

INTRODUCTION: Human adiponectin (ApN) is a 30 kDa glycoprotein of 244-amino acids which is extensively produced by adipocytes. ApN acts via two receptors, namely adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Studies have shown the presence of Adipo-R1 and Adipo-R2 expression immunohistochemically in human colorectal cancers (CRCs). However, only a few studies exist which investigated effects of adiponectin receptor expression on CRC characteristics. OBJECTIVES: In the present study, we aimed to explore Adipo-R1/-R2 expression in human colorectal cancers and any association with clinicopathological characteristics and survival. MATERIALS AND METHODS: The study enrolled 58 colorectal cancer patients with tumor resection and a control group of 30 subjects with normal colon mucosa. RESULTS: Positivity for Adipo-R1/-R2 expression was significantly more common in the control group in comparison to the patient group (both p<0.001). There was no significant association between Adipo-R1/-R2 expression and clinicopathological characteristics including age, sex tumor location, pTNM stage, Duke's stage, metastasis, histological differentiation, perineural invasion, venous invasion sex, lymphatic invasion, cancer-related mortality, tumor size and recurrence. Adipo- R1/-R2 positivity was also not significantly linked to progression-free or overall survival [p values (0.871, 0.758 ) and (0.274, 0.232), respectively]. CONCLUSIONS: Although significantly reduced Adipo-R1/-R2 expression was found in colorectal cancer patients, it had no influence on survival.

Lack of prognostic significance of SOCS-1 expression in colorectal adenocarcinomas.

INTRODUCTION: Recent studies have indicated that down-regulation of the suppressor of cytokine signaling-1 (SOCS-1) gene results in tumor formation and that SOCS-1 acts as a tumor suppressor gene. SOCS-1 has been also suggested to function as a tumor suppressor with colorectal cancer. OBJECTIVES: In the present study, we aimed to determine the association of SOCS-1 expression in colorectal cancer tissues with clinicopathologic characteristics immunohistochemically and also to identify its prognostic significance. MATERIALS AND METHODS: SOCS-1 expression was studied immunohistochemically in 67 patients diagnosed with resected colorectal carcinomas and 30 control subjects. RESULTS: SOCS-1 expression was found in 46.3% of tumor tissues and 46.7% of the control group. Statistical analyses did not establish any significant association between SOCS-1 expression and clinicopathologic characteristics. Also, no significant association with SOCS-1 expression was found using progression-free survival and overall survival analyses (p=0.326 and p=0.360, respectively). CONCLUSIONS: Our results show that SOCS-1 has no prognostic significance in colorectal cancer.

The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B.

BACKGROUND/AIMS: To investigate the relationship between gamma-glutamyl transpeptidase (GGT) levels and histopathological status determined by biopsy in patients with chronic hepatitis B and C. MATERIALS AND METHODS: Patients with chronic hepatitis B and C who were referred to the Uludag University Faculty of Medicine Gastroenterology outpatient clinic between January 2005-January 2011 and underwent liver biopsy were included in the study. Overall, 246 patients with hepatitis B and 151 patients with hepatitis C were enrolled. According to the evaluation based on the Ishak score, patients with a histological activity index (HAI) between 0-12 were defined as low activity, and those with an HAI between 13-18 were defined as high activity. In addition, patients with a fibrosis score of 0-2 were defined as low fibrosis, and those with a score between 3-6 were defined as high fibrosis; comparisons were made accordingly. RESULTS: In patients with hepatitis B, the mean GGT level was 38.86±42.4 (IU/L) in the low activity group and 60.44±44.4 (IU/L) in the high activity group (p<0.05). In hepatitis B patients, the mean GGT level was 26.89±14.83 (IU/L) in the low fibrosis group, whereas it was 65.60±59.7 (IU/L) in the high fibrosis group (p<0.001). There was no significant difference between HAI and fibrosis group with regard to GGT levels in the hepatitis C patients. CONCLUSION: In conclusion, it is proposed that in patients with chronic viral hepatitis, GGT levels can be taken into consideration to predict advanced histological liver damage, especially in patients with hepatitis B.

Lack of any prognostic relationship between adiponectin receptor (Adipo R1/R2) expression for early/advanced stage gastric cancer.

INTRODUCTION: Adiponectin (ApN) is a complement C1q-related protein, mainly secreted from adipose tissue, that signals through ApN receptor 1 (Adipo-R1) and ApN receptor 2 (Adipo-R2). Low serum ApN concentrations are associated with obesity-related malignancies. However, there are very few studies on any prognostic role of ApN receptors in gastric cancer. OBJECTIVES: The aim of this study is to investigate the relationship between AdipoR1/R2 expression and early/advanced stage gastric cancer in terms of clinicopathologic characteristics and survival. MATERIALS AND METHODS: Eighteen patients with early and 39 with advanced stage gastric cancer who underwent surgical gastric resection were included in this study. RESULTS: Adipo-R1 expression was low in 2 of the 18 patients with early stage gastric cancer (11.1%), while 4 had low Adipo-R2 expression (22.2%). In those with advanced stage gastric cancer, 7 of 39 had low Adipo-R1 expression (17.9%) and 16 had low Adipo-R2 expression (41%). Adipo-R2 expression was significantly higher (p=0.011) in moderately differentiated tumors when compared to well-differentiated tumors. While there was nearly a statistically significant relationship between TNM stage (T, tumor size; N, regional lymph node; M, whether distant metastases exist) and Adipo-R2 expression (p=0.054), there was no relationship between Adipo-R1/-R2 expression with tumor stage and survival. CONCLUSION: Adipo-R1/-R2 expression has no prognostic significance of in early/advanced stage gastric cancer.

Gallstone disease does not predict liver histology in nonalcoholic fatty liver disease.

BACKGROUND/AIMS: We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score. METHODS: We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy. RESULTS: Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84). CONCLUSIONS: The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.

Prospective validation of the Glasgow Blatchford scoring system in patients with upper gastrointestinal bleeding in the emergency department.

BACKGROUND/AIMS: This study aimed to allow decision-making about hospitalization or discharge using the Glasgow Blatchford Scoring system, a risk analysis performed using basic laboratory and clinical variables, in patients presenting to the Emergency Department with upper gastrointestinal system bleeding. MATERIALS AND METHODS: This prospective, observational study conducted in the Emergency Department of a university hospital enrolled patients aged ≥18 years, who presented to the Emergency Department with upper gastrointestinal system bleeding between June 2009 and December 2010. For all patients, Glasgow Blatchford Scoring scores were calculated, and the patients were classified into two groups as high-risk and low-risk patients. RESULTS: A total of 160 subjects with upper gastrointestinal system bleeding were enrolled in the study. Mean Glasgow Blatchford Scoring scores were 7.1 ± 3.8 for 71 low-risk subjects and 11.7 ± 2.9 for 89 high-risk subjects, and the difference between the two groups was statistically significant (p<0.001). When the performance of the Glasgow Blatchford Scoring system was evaluated in the determination of high risk, the sensitivity and specificity were 100% and 1.41%, respectively, for a cut-off value of Glasgow Blatchford Scoring >0, 100% and 16.9% for a cut-off value of Glasgow Blatchford Scoring >3, 96.63% and 36.62% for a cut-off value of Glasgow Blatchford Scoring >5, and 86.52% and 69.01% for a cut-off value of Glasgow Blatchford Scoring >8. In the receiver operating characteristic curve analysis, for Glasgow Blatchford Scoring in the high-risk estimation, the area under the curve was found to be 0.82 (95% CI: 0.75-0.88), and this value was statistically significant (p=0.0001). CONCLUSIONS: The Glasgow Blatchford Scoring system, which may be easily calculated based on laboratory and clinical variables, seems to be a useful scoring system for risk analysis of all patients with upper gastrointestinal system bleeding admitted to the Emergency Department.

Characterization of nonalcoholic fatty liver disease unrelated to the metabolic syndrome.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MS). However, not all patients with the MS will develop NAFLD and not all patients with NAFLD have the MS. We sought to investigate the differences between patients with biopsy-proven NAFLD with and without the MS. METHODS: A total of 357 consecutive patients with biopsy-proven NAFLD were analysed. Of them, 216 patients had nonalcoholic steatohepatitis (NASH) and 96 a fibrosis score ≥ 2. The MS was defined as ≥ 3 of the ATP III criteria. RESULTS: A total of 214 patients with NAFLD met the criteria for the MS, while the remaining 143 did not. In NAFLD patients with the MS, homeostasis model of insulin resistance (P = 0·03; OR, 1·06; 95% CI, 1·023-1·25 per unit increase) and diabetes (P = 0·01; OR, 1·2; 95% CI, 1·1-2·4) were independent predictors of NASH. In NAFLD patients without the MS, the only variable independently associated with NASH was haemoglobin (P = 0·007; OR, 1·9; 95% CI, 1·4-3·6 per 50 g/L increase). Alanine aminotransferase (P = 0·03; OR, 1·04; 95% CI, 1·006-1·11 per 10 U/L increase) was an independent predictor of fibrosis ≥ 2 in NAFLD patients with the MS, while haemoglobin (P = 0·02; OR, 1·4; 95% CI, 1·2-1·9 per 50 g/L increase) was the only variable significantly associated with fibrosis ≥ 2 in NAFLD patients without the MS. CONCLUSIONS: Increased haemoglobin in NAFLD subjects without MS should be considered in the selection of cases for histological assessment.

Serum pigment epithelium-derived factor levels are increased in patients with biopsy-proven nonalcoholic fatty liver disease and independently associated with liver steatosis.

BACKGROUND: Increased serum concentrations of pigment epithelium-derived factor (PEDF) have been linked to the metabolic syndrome in the general population. However, the relationship between serum PEDF and nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, remains unknown. METHODS: We assayed serum PEDF levels in 156 patients with biopsy-proven NAFLD and 103 nonsteatotic control subjects who were matched for age and sex. The association between levels of PEDF and clinical, biochemical, and histological phenotypes was examined. RESULTS: NAFLD patients had significantly higher serum PEDF levels (1.97±0.50 µg/mL) than control subjects (1.51±0.49 µg/mL, Student's t test, P<0.001). Multivariable-adjusted stepwise regression analysis showed that PEDF ([beta]=0.32, t=3.13, P=0.002) and triglycerides ([beta]=0.22, t=2.23, P=0.02) were, in the order they entered into the model, the main independent predictors of steatosis scores in our patients with NAFLD. CONCLUSIONS: Serum PEDF levels are significantly increased in patients with biopsy-proven NAFLD and are associated with liver steatosis independently of traditional risk factors.

A case of torsion of the wandering spleen presenting as hypersplenism and gastric fundal varices.

Wandering spleen is the displacement of the spleen from its normal location due to the loss or weakening of ligaments that hold the spleen in the left upper quadrant. The possibility of torsion of the spleen is high due to the long and mobile nature of the vascular pedicle. Generally, cases are asymptomatic. Under conditions of delayed diagnosis, symptoms of splenomegaly, left portal hypertension, gastric fundal varices, and hypersplenism may present as a result of development of vascular congestion associated with chronic torsion. There are only a few cases in the literature reporting the association of wandering spleen and fundal varices. We report herein the case of a 55-year-old female who admitted to our clinic with complaints of fatigue and epigastric pain. She was determined to have gastric fundal varices and hypersplenism secondary to the development of left portal hypertension due to chronic splenic torsion.

Cyclooxygenase-2 expression and its association with angiogenesis, Helicobacter pylori, and clinicopathologic characteristics of gastric carcinoma.

Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.

Crohn's colitis with extraintestinal manifestations: a case report.

The etiopathogenesis of inflammatory bowel disease remains unclear, with various extraintestinal features often found with the disease. Sometimes more than one extraintestinal finding is found in the same patient. In this case report, a patient with more than one extraintestinal manifestation of Crohn's disease is presented. Extensive thrombi in the venous system and pyoderma gangrenosum in the left lower extremity was observed but there was complete recovery following treatment with both systemic and topical agents.