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.

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.

Effect of Clinical, Endoscopic, Radiological Findings, and Complications on Survival in Patients with Primary Gastrointestinal Lymphoma.

BACKGROUND: The purpose of this study was to evaluate the clinical, endoscopic, and radiological characteristics, complications, survival outcomes, and prognostic factors of patients with primary gastrointestinal lymphoma. METHODS: This study retrospectively analyzed the demographic, laboratory, endoscopic, and radiological characteristics and treatment outcomes of 43 patients with newly diagnosed primary gastrointestinal lymphoma. RESULTS: The median age was 62 years (range: 26-83). The primary lesion location was the gastric in 33 (77%) patients and the intestinal in 10 (23%) patients. The most common lesions were the corpus (33%) and corpus+antrum (24%) in primary gastric lymphoma and the ileum (60%) in primary intestinal lymphoma. The most common endoscopic findings were diffuse infiltrative lesion (23%) and massforming (33%), while the most common computed tomography finding was wall thickening (53%). Wall thickening and mass-forming at computed tomography were greater in primary intestinal lymphoma than in primary gastric lymphoma (P = .034). Complications were observed in 9 (21%) patients and 13 (31%) patients who underwent surgery. Complication and surgery rates were higher in primary intestinal lymphoma than in primary gastric lymphoma (P = .003 and P = .014, respectively). Five-year overall survival and 5-year eventfree survival rates were 75% and 72%, respectively. Univariate analysis showed that intestinal involvement, advanced clinical stage, a high International Prognostic Index score, mass-forming and wall thickening at computed tomography, extranodal involvement, and complication were found to adversely affect survival. Multivariate analysis revealed that intestinal involvement and a high International Prognostic Index score were independent prognostic factors for overall survival and event-free survival. CONCLUSION: Patients with primary gastrointestinal lymphoma with intestinal involvement and high International Prognostic Index score should be followed closely.

Real-Life Data on Sofosbuvir/Ledipasvir in Patients with Chronic Viral Hepatitis C Genotype 1b: A Single-Center Experience.

BACKGROUND: The course of hepatitis C disease has changed with the use of direct-acting antiviral drugs in the treatment of the disease. The aim of this study was to evaluate the real-life efficacy and safety of the sofosbuvir/ledipasvir drug regimen in the treatment of patients with genotype 1b. METHODS: Treatment-naive or -experienced 49 genotypes 1b patients treated with sofosbuvir/ledipasvir participated in the study. Laboratory and hepatitis C virus RNA values were evaluated at baseline, week 12, and week 24 of treatment (36th week for those who received 24 weeks of treatment). RESULTS: The sustained virologic response rate was 100% in patients who completed treatment. At the end of the study, there was a significant decrease in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and alpha-fetoprotein levels (P = .000014, P = .000581, P = .000012, and P = .000821), respectively. Renal function tests (creatinine, estimated glomerular filtration rate) worsened (P = .003 and P = .007, respectively). Hepatocellular carcinoma (HCC) was developed in 2 patients during post-treatment follow-up. In Kaplan-Meier analysis, the probability of not developing HCC was 86.5% at 26 months. CONCLUSION: The sofosbuvir/ledipasvir combination is effective in treating genotype 1b chronic hepatitis C with high sustained virologic response rates. Because there are few drug interactions, it may be a suitable option for patients taking multiple medications or who are transplant recipients. Renal function should be monitored closely during and after treatment, as there is a risk of worsening renal function after treatment.

Hepatitis B Virus Screening and Real Life Data in Patients with Solid Tumor Receiving Chemotherapy.

BACKGROUND: Reactivation of the hepatitis B virus (HBV) either during or after chemotherapy may cause serious and sometimes fatal hepatitis. All patients undergoing chemotherapy should therefore be screened in terms of HBV before chemotherapy. The purpose of this research was to identify HBV screening rates in patients with solid cancer undergoing parenteral chemotherapy and to determine the outcomes of patients undergoing HBV screening. METHODS: Data for patients undergoing parenteral chemotherapy for solid cancer from January 1, 2012 to December 30, 2018 were retrieved from our electronic health record patient files in this retrospective study. Screening was defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) tests carried out within six months prior the first chemotherapy session. RESULTS: Four thousand fifty-eight (63%) of the 6440 patients who underwent parenteral chemotherapy were screened for HBsAg and/or HBcAb. The proportions of patients screened for HBsAg and HBcAb improved from 38.8% (2012) to 76.3% (2018), and from 0.2% (2012) to 43% (2018), respectively (P<0.001). The HBsAg and HBcAb positivity rates were 2.9% and 36.5%, respectively. Antiviral prophylaxis was started in 11.8% of HBsAg-negative/HBcAb-positive patients and 40.5% of HBsAg-positive patients. HBV reactivation did not occur in patients receiving antiviral prophylaxis, but was identified in 7.2% of HBsAg-positive patients and 0.6% of HBsAg-negative/HBcAb-positive patients without antiviral prophylaxis. CONCLUSION: Although HBV screening rates before chemotherapy are increasing among solid cancer patients, the rate of initiation of antiviral prophylaxis is still low. It is therefore important to raise awareness regarding HBV reactivation during/after chemotherapy.

Sociodemographic characteristics and clinical risk factors of Helicobacter pylori infection and antibiotic resistance in the Eastern Black Sea region of Turkey.

BACKGROUND/AIMS: The aim of this study was to assess the clinical and sociodemographic risk factors of Helicobacter pylori infection and antibiotic resistance in the eastern Black Sea region of Turkey. MATERIALS AND METHODS: In total, 344 patients with dyspeptic symptoms who completed an extended questionnaire were enrolled in the study. Diagnosis of H. pylori infection was made by rapid urease test, histopathological investigation, and culture. Susceptibility of H. pylori strains was assessed by agar dilution (amoxicillin, tetracycline, metronidazole, levofloxacin) and E-test (clarithromycin) methods. RESULTS: The H. pylori positivity rate was 40.4% (139/344). Logistic regression analysis indicated that age and the presence of duodenal ulcer were independent risk factors associated with H. pylori positivity (odds ratio (OR): 0.96, 95% CI: 0.93-0.99, p=0.013; OR: 5.42, 95% CI: 1.96-14.98, p=0.001, respectively). Of 104 H. pylori-positive cultures, 43 strains (41%) were susceptible to all antibiotics, whereas 61 (59%) were resistant to at least one antibiotic. H. pylori resistance rates were 34% for levofloxacin, 31.1% for metronidazole, 28.2% for clarithromycin, 2.9% for amoxicillin, and 1% for tetracycline. Logistic regression analysis indicated that previous use of clarithromycin was the only independent risk factor for H. pylori resistance (OR: 6.25, 95% CI: 1.59-24.52, p=0.009). CONCLUSION: An understanding of the risk factors for H. pylori positivity and antibiotic resistance in an extended anamnesis may affect treatment choice and facilitate H. pylori eradication. In regions where antibiotic resistance rates are elevated, performing antibiotic susceptibility tests may lead to effective eradication treatment.

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.

The relationship between fibrosis and nodule structure and esophageal varices.

BACKGROUND/AIMS: The aim of the present study was to evaluate the histopathological findings of cirrhosis together with clinical and laboratory parameters, and to investigate their relationship with esophageal varices that are portal hypertension findings. MATERIALS AND METHODS: A total of 67 (42 male and 25 female) patients who were diagnosed with cirrhosis were included in the study. The mean age of the patients was 51.6±19.0 (1-81) years. The biopsy specimens of the patients were graded in terms of fibrosis, nodularity, loss of portal area, central venous loss, inflammation, and steatosis. The spleen sizes were graded ultrasonographically, and the esophageal varices were graded endoscopically. RESULTS: In the multivariate regression analysis, there was a correlation between the advanced disease stage (Child-Pugh score odds ratio (OR): 1.47, 95% confidence interval (CI): 1.018-2.121, p=0.040), presence of micronodularity (OR: 0.318, 95% CI: 0.120-0.842, p=0.021), grade of central venous loss (OR: 5.231, 95% CI: 1.132-24.176, p=0.034), and presence of esophageal varicose veins. CONCLUSION: Although thrombocytopenia and splenomegaly may predict the presence of large esophageal varices, cirrhosis histopathology is the main factor in the presence of varices.

Higher Thrombin-Antithrombin III Complex Levels May Indicate Severe Acute Pancreatitis.

AIM: Coagulation disorders may develop in association with severe acute pancreatitis (AP). Plasma thrombin-antithrombin III complex (TAT) levels are one of the principal markers of coagulation disorder. The purpose of this study was to evaluate TAT and other hemostatic parameters in patients with AP and to examine whether or not these parameters indicate the severity of AP. METHOD: Forty-six patients with AP (14 severe, 32 non-severe) and a 30-member healthy control group were recruited. The severity of AP was determined using the revised Atlanta classification. ELISA was used to measure patients' plasma TAT levels. RESULTS: The TAT levels of AP patients at presentation were higher than those of the control group (p = 0.005). The plasma TAT levels of patients with severe AP were also significantly higher than those of patients with non-severe AP (p = 0.05) and of the control group (p < 0.001). The general accuracy, sensitivity and specificity of TAT levels in predicting the severity of AP were 77.4, 77.8, and 77.3% respectively. CONCLUSION: The coagulation cascade was activated in the AP patients in our study, and this was shown to become more pronounced as severity of the disease increased. Plasma TAT levels at the time of presentation in patients with AP can be used as a marker for predicting the severity of the disease.

Plasma viscosity: a potential predictor of both medical treatment response and clinical stage of ulcerative colitis.

AIM: Ulcerative colitis (UC) is one of the major forms of chronic relapsing inflammatory bowel diseases. The ability to identify type, severity and responsiveness to therapy of UC using laboratory parameters has long been the aim of clinical studies. The aim of this study was to assess the relation betweenplasma viscosity (PV) and disease activity and response to medical treatment in patients with UC. MATERIAL AND METHODS: The study included 105 patients with UC and 42 healthy volunteers. Blood samples were assessed for PV, erythrocyte sedimentation rate (ESR), high sensitive C-reactive protein (hs-CRP), D-dimer, and fibrinogen. RESULTS: Patients with UC were grouped according to disease activity, i.e. active (n= 59) and remission (n= 46). PV was higher in those with active UC compared with those with UC in remission or healthy subjects. It was significantly higher in both UC refractory to steroid compared to UC responsive to steroid (p< 0.001) and UC refractory to cyclosporine compared to UC responsive cyclosporine (p= 0.003). IncreasedSimple Clinical Colitis Activity Index (SCCAI), Endoscopic Grading Scale (EGS), and Histological Disease Activity (HAD) scores were significantly associated with higher PV in patients with UC. CONCLUSION: PV is a useful marker in predicting response to steroid or cyclosporine treatment in patients with active UC. It could be replaced by ESR or hs-CRP as a measure of the acute phase response in UC since it is sufficiently sensitive. These findings may help identify patients with active UC who will require colectomy. KEY WORDS: Biomarkers, Disease activity, Medical treatment, Steroid-refractory ulcerative colitis, Ulcerative colitis.

[Inflammatory bowel disease and pulmonary embolism: Because of 3 cases]. / Inflamatuvar bagirsak hastaligi ve pulmoner emboli: 3 olgu nedeniyle.

Thromboembolic complications are an important cause of morbidity and mortality in inflammatory bowel diseases (IBD). Thromboembolic events are observed more frequently during acute flare of the disease, especially patients received steroid therapy. Increase in awareness and especially anticoagulation prophylaxis in these patients are extremely important. In this article, three cases with diagnosed pulmonary thromboembolism (PE) were presented accompanied by the current literature.

The relationship of recurrent aphthous stomatitis and Helicobacter pylori, cytokine gene polymorphism and cobalamin.

BACKGROUND/AIMS: The aim of the present study was to investigate whether Helicobacter pylori causes or triggers recurrent aphthous stomatitis (RAS) through cytokine gene polymorphism and/or cobalamin deficiency. MATERIALS AND METHODS: Thirty-six patients with RAS and 130 patients without RAS were genotyped for IL-1ß (-511C/T) and IL-6 (-174G/C) and evaluated for H. pylori infection and serum cobalamin level. RESULTS: The patient groups according to RAS had similar rates of H. pylori gastritis and interleukin genotypes/alleles, and there was a non-significant difference between serum cobalamin levels (p>0.05). RAS patients with H. pylori gastritis showed a higher frequency (51.9%) of GC IL-6 genotype than RAS patients without H. pylori gastritis (11.1%) (p=0.036). Non-GG genotype and C allele were increased in patients without RAS and with H. pylori gastritis (p<0.05). Patients with H. pylori gastritis showed a lower value of serum cobalamin without statistical significance, although this difference was more prominent in RAS patients (p=0.07). CONCLUSION: The carriage of the C allele of IL-6 may lead a susceptibility to chronic gastric inflammation after contamination with H. pylori. If H. pylori infection is justified as a predisposing factor for RAS and its severity by further studies, we can speculate that subjects with genetic susceptibility to this infection may benefit from H. pylori eradication treatment with respect to RAS.

Autonomic neuropathy and gallbladder motility in patients with liver cirrhosis.

BACKGROUND/AIMS: Impaired gallbladder motility has been suggested as a contributor to increased incidence of gallstones in patients with liver cirrhosis. The purpose of this study was to determine gallbladder function and its relation with autonomic neuropathy in liver cirrhosis. MATERIALS AND METHODS: Gallbladder function was measured using ultrasonography in 48 patients with liver cirrhosis and in 31 controls. Autonomic neuropathy tests were applied in patients with liver cirrhosis. Patients with liver cirrhosis were analyzed in subgroups according to the severity of disease using the Child-Pugh classification. RESULTS: Fasting gallbladder volume was 16.2 mL (range: 2.1 mL-71.9 mL) in patients and 17.6 mL (range: 4.9 mL-76.6 mL) in controls. There were no differences in fasting gallbladder volume among the study groups (p>0.05). Gallbladder ejection fraction was significantly higher in patients compared with controls (84% vs. 65%) (p<0.001). No correlation was found between gallbladder ejection fraction and autonomic neuropathy (p>0.05). CONCLUSION: Our results indicate that liver cirrhosis does not impair gallbladder emptying, and that there is no association between gallbladder motility and autonomic neuropathy. Further investigations are required to explain increased gallbladder motility in liver cirrhosis.

Low eradication rate of Helicobacter pylori with triple 7-14 days and quadriple therapy in Turkey.

AIM: The eradication rate of Helicobacter pylori (H pylori) shows variation among countries and regimens of treatment. We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication. METHODS: One hundred and sixty-four H pylori positive patients (68 males, 96 females; mean age: 48+/-12 years) with duodenal or gastric ulcer without a smoking history were included in the study. The patients were divided into three groups according to the treatment regimens. Omeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1 g were given twice daily for 1 week (Group I) and 2 weeks (Group II). Patients in Group III received bismuth subsitrate 300 mg, tetracyline 500 mg and metronidazole 500 mg four times daily in addition to Omeprazole 20 mg twice daily. Two biopsies each before and after treatment were obtained from antrum and corpus, and histopathologically evaluated. Eradication was assumed to be successful if no H pylorus was detected from four biopsy specimens taken after treatment. The effects of factors like age, sex, H pylori density on antrum and corpus before treatment, the total H pylori density, and the inflammation scores on the rate of H pylori eradication were evaluated. RESULTS: The overall eradication rate was 42%. The rates in groups II and III were statistically higher than that in group I (P<0.05). The rates of eradication were 24.5%, 40.7% and 61.5% in groups I, II and III, respectively. The eradication rate was negatively related to either corpus H pylori density or total H pylori density (P<0.05). The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55 yr vs 39 yr, P<0.001). No correlation between sex and H pylori eradication was found. CONCLUSION: Our rates of eradication were significantly lower when compared to those reported in literature. We believe that advanced age and high H pylori density are negative predictive factors for the rate of H pylori eradication.