Effectiveness and safety of sofosbuvir/ledipasvir ± ribavirin treatment in liver and/or renal transplant patients with chronic hepatitis C: A single-center experience.

OBJECTIVE: Successful treatment is possible with novel direct-acting oral antiviral agents in solid organ transplant patients with hepatitis C. In this study, the effectiveness and safety of sofosbuvir/ledipasvir ± ribavirin treatment in liver and/or renal transplant patients with chronic hepatitis C were evaluated. MATERIALS AND METHODS: A total of 23 liver and/or renal transplant patients who received sofosbuvir/ledipasvir ± ribavirin for chronic hepatitis C over 12 or 24 weeks were enrolled in the study. The treatment response, clinical and laboratory adverse effects, and effect on immunosuppressive drug levels were assessed. RESULTS: A total of 12 patients had undergone renal transplantation and 11 had undergone liver transplantation. All of the renal transplant patients and 91% of liver transplant patients had genotype 1. In total, 10 renal transplant patients and 4 liver transplant patients had treatment experience. Two renal transplant patients and one liver transplant patient had compensated cirrhosis. Nine renal transplant patients were on tacrolimus, and two were on cyclosporine; all of the liver transplant patients were on tacrolimus-based immunosuppressive therapy. While hepatitis C RNA was negative in 75% of renal transplant patients and 91% of liver transplant patients at week 4, it was negative in all of the patients at the end of treatment and 12 weeks after treatment. Significantly reduced hemoglobin levels were observed in patients administered ribavirin during treatment (p = 0.01). There were no significant differences between the baseline and treatment period values of mean creatinine, estimated glomerular filtration rate, bilirubin, and tacrolimus levels. There were no adverse effects leading to treatment discontinuation. CONCLUSION: Sofosbuvir/ledipasvir ± ribavirin is quite safe and effective in hepatitis C treatment after liver and/or renal transplantation.

Local Immune Response in Helicobacter pylori Infection.

There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-ß, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-ß mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients.

Effect of prophylactic versus preemptive lamivudine treatment and tenofovir on HBsAg+ kidney transplant recipients.

OBJECTIVES: Chronic hepatitis B virus infection remains a clinical problem for HBsAg (+) kidney transplant recipients. Lamivudine is the approved treatment; however, there are contrary views about optimal initiation. In case of resistance, novel nucleoside analogs should be considered but experience is limited. MATERIALS AND METHODS: The study was a retrospective cohort study that included 58 HBsAg (+) kidney transplant recipients. Medical records were reviewed for nucleoside analogs, viral replication, and graft/hepatic functions. Prophylactic and preemptive lamivudine modalities were compared to reveal optimal initiation. Additionally, novel nucleoside analogs were evaluated for safety and efficacy. RESULTS: The graft/patient survival rates for HBsAg (+) recipients were the same as those of hepatitis-free recipients (P = .18). Prophylactic group had 24 and the preemptive had 34 patients. In the prophylactic group, there were fewer hepatic dysfunctions (12.5% vs. 30%, P = .12), viral breakthroughs (16% vs. 32%, P = .17) and elevated alanine aminotransferase concentrations (37% vs. 52%, P = .24), however these did not reach statistical significance. Progressive hepatic dysfunction was observed in 5 patients. Treatment was altered to tenofovir (n = 4) and adefovir (n = 1), and adequate virologic/biochemical response was achieved. These nucleoside analogs were almost as safe as lamivudine, as there were no significant differences among proteinuria (4740 ± 9480 vs 1250 ± 430 mg/L; P = .60) and estimated glomerular filtration rate (1.23 ± 0.37 vs 1.10 ± 0.35 mL/s; P = .33) CONCLUSIONS: Lamivudine is an efficient means of providing comparable graft/patient survival with hepatitis-free kidney transplant recipients. The prophylactic initiation of lamivudine may be better in preventing hepatic dysfunction. Tenofovir can be an effective and safe treatment for lamivudine-resistant kidney transplant recipients.

The assessment of carotid intima-media thickness, lipid profiles and oxidative stress markers in Helicobacter pylori-positive subjects.

BACKGROUND/AIMS: Helicobacter pylori infection has been suggested to be associated with atherosclerosis. The issue is still controversial. It is well known that abnormal lipid profile and oxidative stress are related to atherosclerosis and the measurement of carotid intima-media thickness. The aim of this study was to investigate carotid intima-media thickness and oxidative stress along with lipid parameters in Helicobacter pylori-positive and -negative subjects. MATERIALS AND METHODS: Thirty Helicobacter pylori-positive subjects and 31 Helicobacter pylori-negative subjects were enrolled. Helicobacter pylori infection was diagnosed by noninvasive tests. Serum total oxidant status and total antioxidant capacity levels were measured. Oxidative stress index was calculated based on total oxidant status/total antioxidant capacity ratio. Traditional cardiovascular risk factors were recorded, and laboratory analysis included measurement of serum triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. carotid intima media thickness was assessed by high-resolution ultrasound. RESULTS: We found that the mean and maximum values of right and overall carotid intima-media thickness in Helicobacter pylori-positive subjects were significantly thicker than in Helicobacter pylori-negatives (p < 0.05). Serum triglycerides levels of Helicobacter pylori-positive subjects were significantly higher than in Helicobacter pylori-negatives (p < 0.05). Total oxidant status, total antioxidant capacity and oxidative stress index values were significantly higher in Helicobacter pylori-positive subjects compared with negatives (p < 0.05). No significant correlation was observed between oxidative stress markers and carotid intima-media thickness values. CONCLUSIONS: Carotid intima-media thickness, total oxidant status, total antioxidant capacity, oxidative stress index, and triglycerides values are increased in Helicobacter pylori-positive subjects compared to Helicobacter pylori-negatives. These data indicated that Helicobacter pylori infection may have a role in atherosclerotic processes.

The impact of hepatitis C virus infection on long-term outcome in renal transplant patients.

BACKGROUND/AIMS: The aim of this study was to determine the effect of hepatitis C virus infection on patient and graft survival and liver function in renal transplant patients. METHODS: 1811 renal transplant patients were included in this study. One hundred renal transplant patients (5.5%) were anti-hepatitis C virus-positive. We evaluated demographic, clinical, biochemical, and serological data of patients and compared patient and graft survivals between hepatitis C virus-positive and -negative renal transplant patients. RESULTS: The median follow-up period was 35.7 months. One hundred (5.5%) patients were anti-hepatitis C virus-positive. There were no differences between anti-hepatitis C virus-positive and -negative renal transplant patients regarding age, etiology of renal disease, number of pre-transplant blood transfusions, and hepatitis B virus coinfection rate. Rate of graft loss in anti-hepatitis C virus-positive renal transplant patients was significantly higher than in anti-hepatitis C virus-negative patients (16.0% vs. 9.2%, p=0.026). Survival analysis revealed that patient survival was similar between anti-hepatitis C virus-positive and -negative renal transplant patients. Graft survival was lower in the anti-hepatitis C virus-positive group than in anti-hepatitis C virus-negative patients, especially after the fifth year of renal transplant (p<0.001). Thirty-three percent of anti-hepatitis C virus-positive patients were positive for hepatitis C virus RNA. Twenty-seven percent of anti-hepatitis C virus-positive patients had persistent alanine aminotransferase elevation. None of the patients developed cirrhosis during the follow-up period. CONCLUSION: Our findings suggest that hepatitis C virus infection in renal transplant patients does not adversely affect patient survival. Long-term graft survival seems to be lower in hepatitis C virus-positive compared to hepatitis C virus-negative renal transplant patients. Nevertheless, renal transplant can be considered as a safe and effective treatment modality in anti-hepatitis C virus-positive patients with end-stage renal disease.

The effect of kidney diseases on survival in liver transplant patients.

BACKGROUND: Liver transplantation (LTx) is a life-saving procedure for patients with chronic end-stage liver disease or acute liver failure. It is well known that kidney diseases such as acute kidney injury (AKI) and chronic kidney disease (CKD) are highly prevalent in LTx patients. We aimed to assess the effect of kidney disease on survival in LTx patients. MATERIALS AND METHODS: In this study, we included 85 patients (mean age 43.7 ± 12.7, male/female 53/32) who underwent orthotopic liver transplantation between 2001 and 2009 and analyzed their medical records and laboratory results. The effect of renal dysfunction including CKD and AKI on survival in LTx patients was assessed by Kaplan-Meier survival analysis. RESULTS: Median duration of follow-up was 48.4 months (2.6-163 months). Before transplantation, eleven patients (12.9%) were diagnosed with CKD and nine (10.5%) with AKI. AKI developed in 17 patients (20%) in the early post-operative phase, among which five had pretransplant CKD. We found that the number of male patients and the number of red blood cell transfusions were statistically higher in LTx patients with AKI than in those without AKI (p < 0.05). Eight patients died in the follow-up period. Estimated survival rates of patients were 93.9, 92.7 and 90.8% at 1st, 3rd and 5th years, respectively. The survival rate of patients with pre-LTx CKD was worse than that of patients with normal kidney function (70.7 vs. 95.8% in the 3rd year, p = 0.043). We also found that the survival rate of patients with post-LTx AKI was lower than in patients with normal kidney function (66.7 vs. 96.6% in the 5th year, p < 0.001). CONCLUSION: Our results suggest that post-LTx AKI determined by age and pre-LTx CKD had a negative effect on survival of LTx patients. These patients should be followed up and carefully managed in the perioperative period with the aim of minimizing the kidney dysfunction.

Utilization of impedance cardiography in noninvasive assessment of hemodynamic status in cirrhotic patients.

BACKGROUND/AIMS: This study aimed to assess hemodynamic alterations noninvasively using a dedicated device Task Force® Monitor providing various hemodynamic data utilizing impedance cardiography and beat-to-beat blood pressure analysis via a vascular unloading unit. METHODS: Forty-seven patients with cirrhosis awaiting hepatic transplantation and 26 healthy volunteers matched for age and gender were enrolled. Basic hemodynamic status of these patients (following temporary interruption of any drugs affecting the cardiovascular system) was evaluated noninvasively by Task Force® Monitor with patients in the supine position. RESULTS: Mean age of the patients was 46 years and 74.5% were male. The etiology of cirrhosis was viral hepatitis in 59.5% and alcoholic cirrhosis in 19.1% of cases, whereas 17% had cryptogenic cirrhosis. 38.3%, 25.5%, and 36.1% of the patients were stratified into groups A, B and C according to the Child-Pugh classification, respectively. Heart rate, cardiac output and cardiac index were significantly higher in patients with cirrhosis compared to the control group. However, diastolic blood pressure, total peripheral resistance and total peripheral resistance index were significantly lower in the cirrhosis group. This situation representing a hyperdynamic circulatory state became more prominent in conjunction with advanced disease severity. CONCLUSIONS: The present study demonstrates that the Task Force® Monitor device is capable of delineating the hyperdynamic circulatory state in cirrhotic patients and satisfactorily indicates differences between controls and patients at diverse levels of severity. Regarding potential applications in clinical practice and research, noninvasive hemodynamic monitoring by Task Force® Monitor may be a reliable and reasonable alternative tool to invasive procedures.

The assessment of carotid intima media thickness and serum paraoxonase-1 activity in Helicobacter pylori positive subjects.

BACKGROUND: The role of inflammation in the pathogenesis and progression of atherosclerosis has been increasingly discussed. Although the seroepidemiological studies have suggested a relationship between Helicobacter pylori (H. pylori) infection and atherosclerosis; the issue is still controversial. It is well known that abnormal lipid profil is related to atherosclerosis and the measurement of carotid-intima media thickness (CIMT) is one of the surrogate marker of atherosclerosis. The serum concentration of high-density lipoprotein (HDL-C) has been known to have an inverse correlation with the development of atherosclerosis. Paraoxonase-1 (PON1) is a major anti-atherosclerotic component of HDL-C. PON1 activity is related to lipid peroxidation and prospective cardiovascular risk. The aim of this study was to investigate CIMT and serum PON1 activities along with lipid parameters in H. pylori positive and negative subjects. METHODS: Thirty H. pylori positive subjects and thirty-one negative subjects were enrolled. H. pylori infection was diagnosed by the presence of positivity of stool H. pylori antigen test or Carbon 14 labeled urea breath test. Serum PON1 activity was measured spectrophotometrically. Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C). We assessed CIMT by high-resolution ultrasound of both common carotid arteries. RESULTS: We found that the mean and maximum values of right and overall CIMT in H. pylori positive subjects were significantly thicker than those of H. pylori negative subjects. There was no significant differences in serum HDL-C, LDL-C, TC levels and TC/HDL-C ratios between two groups. Serum TG levels of H. pylori positive subjects were significantly higher than those of H. pylori negative subjects (p = 0.014). We found that PON1 activities were significantly lower in H. pylori positive subjects compared with negative subjects. No significantly correlation was observed between PON1 and CIMT values. CONCLUSIONS: There is an increase in CIMT values in patients with H. pylori positive compared to H. pylori negative subjects. PON1 activity decrease significantly in H. pylori positive subjects. However, an association between PON1 and CIMT was not found. These data indicated that H. pylori may have a role in atherosclerotic processes, however, further studies are needed to evaluate the exact mechanisms.

Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter epidemiologic survey.

AIM: To investigate the epidemiologic and clinical characteristics of inflammatory bowel disease (IBD) patients in a large multicenter, countrywide, hospital-based study in Turkey. MATERIALS AND METHODS: Twelve centers uniformly distributed throughout Turkey reported through a questionnaire the new IBD cases between 2001 and 2003. The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has been reported per 100,000 people. Epidemiologic features and clinical characteristics of both diseases were analyzed. RESULTS: During the study period, 661 patients of UC and 216 patients of CD were identified. The incidence in the referral population was 4.4/100,000 and 2.2/100,000 for UC and CD, respectively. The age of the patients showed the characteristic biphasic distribution with 2 peaks between 20 and 30 and 50 and 70 years. A male predominance was observed in both diseases. A history of smoking was detected in 15.5% of UC patients and 49.3% of patients with CD. Family history was positive in 4.4% in UC and 8.3% in CD patients. Concomitant amebiasis was observed in 17.3% of patients with UC and 1.3% of patients with CD. A history of appendectomy was reported in 15% of patients with CD and only 3% of patients with UC. Both extraintestinal and local complications were more frequent in CD patients, whereas arthritis was most common in both diseases. CONCLUSIONS: IBDs are frequently encountered in Turkey. IBD incidence is lower than North and West Europe but close to Middle East in our country. The majority of IBD cases are diagnosed in young people (20 to 40 y) with predominance in males. The rate of both intestinal and extraintestinal complications in our population was low when compared with the data reported in the literature. IBD and especially UC, can coexist with amebiasis or become manifest with amebic infestation. The presence of concomitant ameba may create confusion and cause dilemmas in the diagnosis and treatment of UC.

High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients.

OBJECTIVES: The importance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in pancreatic carcinoma development is not known. To reveal the putative connection of TRAIL and TRAIL receptor expression profile to this process, we analyzed and compared the expression profile of TRAIL and its receptors in pancreatic tissues of both noncancer patients and patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Thirty-one noncancer patients and 34 PDAC patients were included in the study. TRAIL and TRAIL receptor expression profiles were determined by immunohistochemistry. Annexin V binding revealed the apoptotic index in pancreas. Lastly, the tumor grade, tumor stage, tumor diameter, perineural invasion, and number of lymph node metastasis were used for comparison purposes. RESULTS: TRAIL decoy receptor 2 (DcR2) and death receptor 4 expression were up-regulated in PDAC patients compared with noncancer patients, and the ductal cells of PDAC patients displayed significant levels of apoptosis. In addition, acinar cells from PDAC patients had higher DcR2 expression but lower death receptor 4 expression. Increased DcR2 expression was also observed in Langerhans islets of PDAC patients. CONCLUSIONS: Differential alteration of TRAIL and TRAIL receptor expression profiles in PDAC patients suggest that the TRAIL/TRAIL receptor system may play a pivotal role during pancreatic carcinoma development.

Prevalence patterns of gastric cancers in Turkey: model of a developing country with high occurrence of Helicobacter pylori.

AIM: In developed countries, there has been a recent increase in the prevalence of adenocarcinoma of the esophagus and cardia, along with a decrease in distal gastric cancers. Little is known regarding the prevalence of these diseases in developing countries. The aim of the present study was to evaluate changes in the prevalence of gastric adenocarcinomas in Turkey as a function of anatomic location. METHODS: Data were retrospectively collected from 16 centers from January 1990 to December 2000. Owing to the exclusion criteria, a total of 4065 cases of tumors of the stomach and distal esophagus were included. Tumors localized to the body, the antrum and pyloric channel were considered distal cancers. Helicobacter pylori (H. pylori) was also detected. RESULTS: Patients' mean age was 60.7 +/- 9 years, with a male : female ratio of 68:32. The ratio of distal/proximal adenocarcinoma was 2,1 [corrected] for the western part of Turkey and 3,8 [corrected] for the eastern part of the country (P < 0.0001), and this did not change during the 11 years. H. pylori was detected significantly less in the west compared to the east for distal tumors (65.7 vs 38.7%, respectively, P = 0.02). CONCLUSION: In Turkey, a developing country with a high H. pylori prevalence, contrary to the state of developed countries, the ratio of distal versus proximal gastric adenocarcinomas has not changed. Geographical distribution should be taken into the account in projecting the changing patterns of gastric cancers.

p27 expression and proliferation in gastrointestinal stromal tumors.

BACKGROUND/AIMS: The p27 is a cyclin-dependent kinase inhibitor which plays a pivotal role in cell proliferation during development and tumorigenesis. Recently, it was shown that low expression of p27 tends to occur in more aggressive neoplasms. In gastrointestinal stromal tumors p27 expression and its correlation with proliferation remain to be elucidated. The aim of the present study was to investigate the expression of p27 and proliferation in gastrointestinal stromal tumors. METHODS: p27 and Ki-67 immunostained tissue sections from 45 gastrointestinal stromal tumors (benign, borderline and malignant) were subjected to quantitative analysis, and p27 labelling index and Ki-67 labelling index were obtained for each case. RESULTS: The mean values of Ki-67 labelling index in the three groups were significantly different (benign, 4.53%; borderline, 9.82%; and malignant, 15.35%) (p<0.05). p27 labelling index was decreased in malignant tumors (10.46%) compared with benign (36.56%) and borderline tumors (21.36%) (p<0.05). Moreover, in each group p27 labelling index exhibited a significant inverse relation to p67 labelling index (p<0.001). CONCLUSION: Our results suggest that decreased levels of p27 labelling index could predict the malignant behavior of gastrointestinal stromal tumors and might be associated with tumor cell proliferative activity.

Hepatic epithelioid hemangioendothelioma treated with orthotopic liver transplantation: a case report.

Hepatic epithelioid hemangiendothelioma is a rare vascular tumor. The clinical course is unpredictable and different treatment modalities are offered depending on the patients condition. Orthotopic liver tranplantation is the choice of treatment in diffuse cases without metastases. A 32 year old woman was admitted to hospital with multiple mass lesions diagnosed by ultrasonography of the liver. Physical examination was normal except for a painless hepatomegaly, and her biochemical tests were within the normal range. Computed tomographic scanning showed the presence of multiple lesions in both lobes, some of which were accompanied by a small degree of calcification. Although these findings were suggestive of hepatic epithelioid hemangioendothelioma, ultrasonographic guided fine needle aspiration biopsy failed to diagnose the exact nature of the lesions. The diagnosis of hepatic epithelioid hemangioendothelioma was confirmed by diagnostic laparotomy and immunohistochemical examination of the specimen by FVIII-RAg, CD34 and CD 31 markers. The patient was treated by orthotopic liver transplantation and had no evidence of tumor 18 months after transplantation. The problems in differential diagnosis and treatment options are discussed in this report of the first case of this rare tumor, treated by orthotopic liver transplantation in Turkey.