Treatment of HCV infection with direct-acting antiviral agents. Real life experiences from the Euro-Asian region.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a common disease that causes liver cirrhosis, hepatocellular carcinoma, and extra hepatic manifestations with high mortality and morbidity rates. This study aimed to present real-life experiences and results of treatment of HCV infection with direct-acting antiviral agents (DAAs) from the Euro-Asian region, including Turkey and Azerbaijan. MATERIALS AND METHODS: A total of 1224 patients with chronic HCV infection were treated with DAAs in accordance with the international guidelines for the management of HCV infection. The mean age was 58.74±14.75 years, with 713 (58.25%) females. The genotypes of the patients were as follows: genotype 1b, 83.36% (n=1024); genotype 1a, 8.08% (n=99); genotype 2, 2.85% (n=35); genotype 3, 3.34% (n=41); genotype 4, 1.71% (n=21); and combined genotypes, 0.32% (n=4). Approximately 808 patients were treated with sofosbuvir-based DAAs with or without Ribavirin for 12 or 24 weeks, whereas 416 patients were treated with the Paritaprevir, Ombitasvir, Ritonavir.Dasabuvir (PROD) regimen with or without Ribavirin for 12 weeks or 24 weeks. RESULTS: At the end of follow-up examinations, 1183 patients (97.93%) had sustained virological response (SVR), 17 (1.40%) died of reasons unrelated to the treatment regimen, 12 had recurrence after treatment, and 129 (10.67%) had adverse events like anemia, itching, and weakness. CONCLUSION: In this large cohort of HCV-infected patients, treatment with DAAs yielded a high overall SVR rate of 97.93%. DAAs were safe and well-tolerated. Thus, the elimination of HCV infection is no longer a dream worldwide.

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 efficiency of endoclips in maintaining the gastrointestinal bleeding-related Dieulafoy's lesion.

BACKGROUND: Dieulafoy's lesion (DL) is a relatively uncommon medical condition characterized by a large tortuous arteriole in the submucosa of any part of gastrointestinal (GI) tract wall that bleeds via erosion likely caused in the submucosal surface by protrusion of the pulsatile arteriole. Compared with other endoscopic hemostatic techniques, clipping alone for DL is limited. AIMS: The aim of the present case series study is to identify common clinical and endoscopic features, rates of occurrence, to review the outcome of endoscopic management of upper GI tract DL, and to illustrate the use and the efficiency of endoclips in maintaining the GI bleeding due to DL. PATIENTS AND METHODS: This case series was conducted at Department of Gastroenterology, Diskapi Yildirim Beyazit Educational and Research Hospital. The patients who were admitted to the emergency department of Diskapi Yildirim Beyazit Educational and Research Hospital underwent gastrointestinal system (GIS) endoscopy between 2008 and 2013 and were assessed retrospectively. Five cases of GI bleeding related to DL were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: The median number of endoscopic hemoclips application in first endoscopy was 4 (2-9). Rebleeding developed in all patients who had hemoclips applied. Re-endoscopy was performed in three of these patients, which controlled the bleeding. Two patients were transferred to surgery. CONCLUSIONS: Combination of endoscopic injection and mechanical therapies seems a suitable method for maintaining upper GIS bleeding due to DL. Also, further studies are needed to better define the best endoscopic approach for the treatment of DL.

Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma.

Colorectal cancer (CRC) is the third most common cause of cancer-related death in Europe. The aim of the present study was to elucidate the efficiency of the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the mean platelet volume (MPV) as tools for the preoperative diagnosis of CRC and their usefulness in the follow-up of CRC. A total of 144 CRC patients, as diagnosed by colonoscopy, and 143 age-matched and sex-matched healthy participants were included in the study. Medical records were used to compare preoperative and postoperative data including hemoglobin levels, platelet counts, MPV, NLR, and PLR. NLR, PLR, and MPV were significantly higher in CRC patients preoperatively, compared with healthy participants. Receiver-operating characteristic curve analysis suggested 2.02 as the cutoff value for NLR [area under the curve (AUC): 0.921, sensitivity: 86%, specificity: 84%], 135 as the cutoff value for PLR, (AUC: 0.853, sensitivity: 70%, specificity: 90%) and 8.25 fl as the cutoff value for MPV (AUC: 0.717, sensitivity: 54%, specificity: 76%). Subgroup analysis showed that NLR, PLR, and MPV levels were also significantly higher in nonanemic CRC patients compared with the control group, which is of great theoretical and clinical value for the early detection of CRC. Surgical tumor resection resulted in a significant decrease in NLR, PLR, and MPV. Our results suggest that NLR, PLR, and MPV may be used as easily available additional biomarkers for CRC in screening the general population, as well as in postoperative follow-up.

The utility of thrombopoietin in predicting liver fibrosis in chronic hepatitis B.

Many noninvasive serum markers have been studied to determine the liver fibrosis score (LFS). In this study, we aimed to investigate the association between thrombopoietin (TPO) levels and the stage of liver fibrosis in patients with chronic hepatitis B (CHB). Seventy-seven patients (64 active and 13 inactive) with CHB were included in this cross-sectional study. Patients were divided into three groups: In group 1, patients with mild or no fibrosis (F0, F1); in group 2, patients with significant fibrosis (F2-F4); and in group 3, inactive CHB carriers. Digital patient records were used to access pre-treatment laboratory findings including HBV DNA, HBeAg, ALT, AST, total bilirubin, PLT, albumin, INR. Liver biopsies were examined by experienced pathologists in our hospital who were blinded to the data of the patients. Serum TPO levels were measured using commercial ELISA kit. Serum TPO levels were significantly lower in patients with active CHB compared with the inactive carriers (528 vs 687.1 p=0.003). There was no statistically significant difference in TPO levels between the patients with and patients without significant fibrosis (568.9 vs 459.8 p=0.367). Correlation analysis with respect to ALT, AST, TPO, HBV-DNA level, platelet count, histological activity index (HAI) and liver fibrosis score was performed. TPO was only weakly positively correlated with AST, ALT and HBV-DNA levels (r=0.269 p=0.018; r=0.341 p=0.002; r=0.308 p=0.006; respectively) and no correlation in TPO with LFS and HAI was found (r=0.140 p=0.270, r=0.162 p=0.201; respectively). TPO was not associated with significant fibrosis (p=0.270). In conclusion, TPO levels were decreased in active CHB patients compared with inactive carriers but there was no correlation between TPO levels and the stage of fibrosis in active CHB.

Significance of serum and ascitic fluid C-reactive protein in differential diagnosis of benign and malignant ascites.

BACKGROUND: The values of C-reactive protein (CRP) can prove useful in determining disease progress. Because of synthesis by the liver, production of CRP in response to inflammation may be attenuated in patients with liver dysfunction. This may result in differences interpreting CRP levels in patient with portal and non-portal hypertension ascites. AIM: The aim of the present study is to assess discriminant value of serum and ascitic fluid CRP, which is easily accessible and inexpensive laboratory marker of inflammation, concentrations for diagnosis of underlying cause of ascites. METHODS: This prospective study was conducted at Diskapi Yildirim Beyazit Educational and Research Hospital Department of Gastroenterology. Patients with ascites were further divided into two subgroups based on underlying cause of ascites: Group 1, patient with ascites due to portal hypertensive etiology (high-gradient ascites); Group 2, patient with ascites due to non-portal hypertensive etiology (low-gradient ascites). RESULTS: A total of 91 patients fulfilling the criteria for a diagnosis of ascites were enrolled in the study. Of these patients, 50 had proven (Group 1) ascites due to portal hypertensive etiology (high-gradient ascites) and 41 had clinical (Group 2) ascites due to non-portal hypertensive etiology (low-gradient ascites). Mean baseline serum and ascites levels of CRP were significantly higher in Group 2 compared to those in Group 1 (p = 0.021, p = <0.0001, respectively). CONCLUSIONS: Increased levels of serum and ascitic fluid CRP were associated with malignant ascites.

IGF-I levels and visceral fat accumulation in colonic neoplasia.

BACKGROUND: IGF-I, visceral obesity, IGF binding protein-3 and insulin are reported to be potential risk factors for colorectal carcinogenesis. Many studies report a relation between obesity, insulin resistance and the risk of colon cancer. This study investigates the association between IGF-I levels, insulin resistance and visceral fat accumulation in patients with colon cancer and adenoma. METHODS: In this cross sectional study, 48 sequential patients were diagnosed with either colorectal adenoma or carcinoma were enrolled. The control subjects were 30 sequential subjects. Serum IGF-I, HOMA insulin resistance index and visceral fat were measured in patients with colorectal adenoma and carcinoma. RESULTS: Serum IGF-I levels were significantly higher in patients with colorectal adenoma and carcinoma compared with controls. Visceral fat accumulation was lower in colorectal carcinoma group compared with colorectal adenoma group, but no statistically significant difference was observed among them and controls. No statistically significant difference was observed in HOMA insulin resistance index, fasting insulin and fasting glucose concentrations among the three groups. No correlation was found between insulin resistance and serum IGF-I levels and visceral fat accumulation. Logistic regression analysis showed that plasma IGF-I concentration was significantly associated with colorectal adenoma and carcinoma. Body mass index and waist circumference were associated with colorectal, carcinoma but were not associated with adenoma. CONCLUSION: In our study we found that, IGF-I levels are associated with colorectal adenomas and carcinomas, independent of insulin resistance and visceral fat accumulation; supporting the hypothesis that an increase in IGF-I levels may be a factor involved in the development of colon cancer.

Mean platelet volume could be possible biomarker in early diagnosis and monitoring of gastric cancer.

Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related deaths worldwide. The early diagnosis of gastric cancer is fundamental in decreasing the mortality rates. It has been shown that MPV level is a sign of inflammation in hepatocellular carcinoma and pancreatic adenocarcinoma. The aim of this study is to examine whether MPV would be a useful inflammatory marker for differentiating gastric cancer patients from healthy controls. Thirty-one gastric cancer patients and 31 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. MPV level was significantly higher in pre-operative gastric cancer patients compared to healthy subjects (8.31 fL vs. 7.85; p: 0.007). ROC analysis suggested 8.25 fL as the cut-off value for MPV (AUC: 0.717, sensitivity: 61%, specificity: 81%). Surgical tumor resection resulted in a significant decrease in MPV level (8.31 fL vs. 7.55 fL; p: 0.001). No significant difference was found in MPV level between the post-operative group and control subjects. We did not find statistically significant difference between MPV and TNM stages. In conclusion, changes in MPV values may be used as an easily available biomarker for monitoring the healthy patients for GC risk and may prompt physicians to make an early diagnosis of GC.

Serum m 30 levels reflects ulcerative colitis activity.

BACKGROUND: Apoptosis plays a role in epithelial and mucosal injury, which is 1 of the mechanisms in the pathogenesis of ulcerative colitis. Apoptotic cells increase as a result of injured mucosa in ulcerative colitis and serum M 30 levels increase in epithelial cell apoptosis. In this study, we aimed to evaluate the relation between M 30 serum levels and ulcerative colitis activity. METHODS: Eighty patients with ulcerative colitis and 40 healthy controls were enrolled into the study. The patient group consisted of 31 extensive colitis, 30 left-sided colitis, and 19 proctitis. The activity of ulcerative colitis was determined with clinical and endoscopic findings. Serum M 30 levels, acute phase reactants, and biochemical tests were analyzed in all subjects. RESULTS: Serum M 30 levels in patients with active ulcerative colitis were significantly higher when compared with the healthy controls (165.6 ± 60.6 and 129.6 ± 37.4; P = 0.003). Serum M 30 levels in active left-sided colitis patients was significantly higher when compared with patients in remission phase (180.6 ± 58.5, 141.5 ± 35.4; P = 0.044). When we exclude patients with ulcerative proctitis, M 30 levels in active ulcerative colitis patients were significantly higher than that the patients in remission phase (174.0 ± 63.5, 135.0 ± 29.9; P = 0.017). CONCLUSIONS: We found that M 30 levels increase in patients with active ulcerative colitis. Our findings support the role of apoptosis demonstrated by serum M 30 levels in the pathogenesis of active ulcerative colitis.

Spontaneous splenic infarction in an elderly cirrhotic patient with multiple comorbidities.

Spontaneous splenic infarction has been seen rarely in cirrhosis and portal hypertension. The clinical presentation can mimic other causes of acute abdominal pain. The diagnosis of the condition is based on clinical findings and splenic imaging. In recent years, ultrasonography and computed tomographic scan have gained in popularity for the diagnosis of splenic infarction. Most reported cases are of focal infarction, and treatment is mostly conservative. Herein, we describe a rare case of spontaneous splenic infarction in an elderly cirrhotic patient with portal hypertension who also had comorbidities. A 72-year-old female previously diagnosed with cirrhosis was admitted for left upper quadrant abdominal pain for two days. Her medical history included cryptogenic cirrhosis, congestive heart failure, chronic obstructive pulmonary disease, and hypertension. Physical examination on admission revealed a palpable splenomegaly. Abdominal ultrasonography revealed splenomegaly and a hypoechoic area with lobulated contours measuring 62 x 35 mm extending from the subcapsular area to the hilus in the middle section of the spleen. Abdominal computed tomographic showed a subcapsular hypodense lesion of the spleen measuring 64 x 58 mm. Doppler ultrasound revealed a wedge-shaped heterogeneous hypoechoic avascular area extending from the central zone to the lateral zone of the spleen. In our case, diagnosis of splenic infarction was made by computed tomographic and Doppler ultrasonography. Our patient received conservative treatment for the underlying diseases. Spontaneous splenic infarction must be kept in mind in cirrhotic patients with underlying comorbidities presenting with left upper quadrant pain.

Acute liver failure due to non-exertional heatstroke after sauna.

Acute liver failure is defined as rapid loss of liver function that patients without previously recognized liver disease sustain a liver damage. Acute liver failure due to non-exertional heatstroke has rarely been reported. We reported here an unusual case of heat stroke induced acute liver failure (ALF) after sauna. A 63 year old man without previously recognized liver and other systemic disease was admitted for loss of consciousness and impaired liver function after sauna. Despite intensive supportive care, ALF developed. Liver transplantation was planned but the patient died on the sixth day of hospitalization. Non-exertional heatstroke induced ALF is a rare and serious condition. ALF caused by non-exertional heatstroke which requires liver transplantation for definitive solution should be kept in mind in early period.

Effects of erdosteine on cyclosporine-A-induced hepatotoxicity in rats.

Cyclosporine A (CsA) is a potent immunosuppressive agent used for organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains one of the major side effects. The use of antioxidants reduces the adverse effects of CsA. The aim of this study was to determine the protective effects of erdosteine on CsA-induced liver injury through tissue oxidant/antioxidant parameters and to evaluate light microscopic alterations in rat-liver tissues. Rats were randomly divided into four experimental groups: The control group received sunflower oil (2 mL/kg/day, per orally; p.o.), while the other groups were treated with CsA (25 mg/kg/day, p.o.) or erdosteine (10 mg/kg/day, p.o.) or CsA+erdosteine, respectively. Serum aspartate aminotransferase and alanine aminotransferase levels, tissue malondialdehyde and nitric oxide levels, and superoxide dismutase, glutathione peroxidase and catalase enzyme activities were measured. Histological examination was performed. CsA caused a significant deterioration in the hepatic function tests, morphology, and gave rise to severe oxidative stress in the liver. Erdostein significantly improved the functional and histological parameters and attenuated the oxidative stresss induced by CsA. Erdostein protects liver tissue against oxygen free radicals and prevents hepatic dysfunction and morphological abnormalities associated with chronic CsA administration.

Prevalence of proximal neoplasms among asymptomatic patients according to distal colorectal findings.

Colorectal cancer has been described in association with hyperplastic polyposis. Only half of proximal colon cancers are associated with distal adenomas. To compare the prevalence of proximal and advanced neoplasia between patients with distal hyperplastic polyps only; with distal adenomas with or without hyperplastic polyps; and with no distal polyps, we retrospectively analyzed data of 1,064 adults who underwent colonoscopy. Of these patients, 3% had neoplasia. Proximal neoplasia occurred in 0.8% of 945 patients with no distal polyps, compared to none of 19 with distal hyperplastic polyps (P > 0.05) and 6% with distal adenomas (P > 0.05). Proximal advanced neoplasia occurred in 0.6% patients with no distal polyps, compared with none with distal hyperplastic polyps (P > 0.05) and 6% with distal adenomas (P > 0.05). In conclusion, patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps.

Association of visceral fat accumulation and adiponectin levels with colorectal neoplasia.

PURPOSE: There are few studies addressing the association between measured values of visceral fat accumulation (VFA), adiponectin, and colorectal neoplasia. Our purpose is to investigate the association of VFA and serum adiponectin levels with colorectal adenoma and carcinoma patients. For this purpose, 54 patients with colorectal adenoma and carcinoma, diagnosed by colonoscopic evaluation, and 50 healthy control subjects were included. Patients were subjected to measurement of VFA and adiponectin level and calculation of insulin resistance. RESULTS: Patients with colorectal carcinoma had lower plasma adiponectin levels compared with controls. VFA level did not differ between patients and controls. Adiponectin level was found to be uncorrelated with VFA in the colorectal cancer and adenoma group. No correlation was found between insulin resistance and plasma adiponectin level and VFA. CONCLUSION: Our findings suggest that decreased plasma adiponectin level may be a factor involved in the development of colon cancer or a secondary effect of the metabolic derangements in colorectal cancer.

Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey.

OBJECTIVE: The aim of this study is to determine the etiologies of serum gamma glutamyltransferase (GGT) elevation and relations between multiple etiologies prevalent in the Pursaklar region of Ankara in Turkey. PATIENTS AND METHODS: The patients referred to the Family Medicine and Internal Medicine departments with various complaints from the Pursaklar region of Ankara between July 2000 and July 2002 were evaluated, and values for GGT, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) levels were determined. GGT elevation was classified as being associated with hepatic, biliary, and other origins. RESULTS: For GGT elevation, hepatobiliary etiologies were more prevalent. The most prevalent hepatic etiology was nonalcoholic steatohepatitis, followed by biliary etiologies. The most prevalent etiology of biliary origin was cholelithiasis. Other etiologies, in order of prevalence, were drug exposure and urinary infection. There were no gender-related differences for distribution of GGT elevation; however, the GGT values for women were higher than those for men.