Murat Kiyici

Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis

BACKGROUND/AIMS Nonalcoholic steatohepatitis (NASH) is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA) in the treatment of NASH. METHODS This prospective study included 44 adult patients (24 men, 20 women) with a mean age of 48.90+/-7.69 years and mean body mass index (BMI) of 29.40+/-3.82. Ten patients had a history of diabetes. Serological markers for viral hepatitis were negative in all patients and there was no history of alcohol or drug abuse. Patients who had autoimmune hepatitis were excluded from the study. Liver biopsy was performed before therapy to confirm the diagnosis. Among NASH patients, 17 normolipidemic cases received UDCA 13 to 15 mg/kg/day (group 1), while hyperlipidemic cases (n=27) received atorvastatin 10 mg/day (group 2) for six months. The BMI, serum lipids, liver function tests and liver density, assessed by computerized tomography, were evaluated before and after the treatment period. The BMI, serum aminotransferase levels, histological parameters (steatosis, inflammation, fibrosis scores) and liver densities were not statistically different between the groups at the beginning of therapy. RESULTS The BMI, serum glucose, and triglyceride levels did not change in either group after the treatment period. In group 1, serum alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) levels reduced significantly, and in group 2, serum cholesterol, aspartate aminotransferase, ALT, alkaline phosphatase and GGT levels reduced significantly. Liver densities increased only in group 2, probably as a result of diminishing fat content of liver. The normalization of transaminases was also more prevalent in group 2. Liver steatosis was closely correlated with liver density, but inflammation and fibrosis were not. CONCLUSIONS The use of atorvastatin in NASH patients with hyperlipidemia was found to be both effective and safe. The benefit of statin and UDCA therapy in normolipidemic patients with NASH requires confirmation with further placebo-controlled trials.

Single-agent irinotecan as second-line treatment for advanced gastric cancer

Aim To investigate the activity and toxicity of irinotecan (CPT-11) as a single agent in patients with advanced gastric cancer after failure of previous 5-fluorouracil-based combination chemotherapy. Patients and methods Sixteen patients with advanced gastric received CPT-11, 350 mg/m2 every 21 days. The median age of the patients was 54.6 years; ECOG performance status was 0-1 in 14 patients and 2 in 2 patients. Dominant metastatic sites included liver, lung, lymph nodes and peritoneum. Results No complete response was observed. Two patients (12.5%) achieved a partial response to treatment. One patient (6.25%) had a minor response. Ten patients (62.5%) had progressive disease on therapy, and 3 patients (18.75%) had stable disease. The median survival of all 16 patients was 5 months. Grade 3 neutropenia was observed in 3 patients (18.75%), grade 4 thrombocytopenia in 1 patient (6.25%), and grade 3 anemia in 1 patient (6.25%). Three patients (18.75%) suffered from grade 3 diarrhea. Conclusions CPT-11 is moderately active and a well-tolerated regimen for selected advanced gastric cancer patients who experience disease progression after receiving first-line treatment.

Lymphocyte subsets and cytokines in ascitic fluid of decompensated cirrhotic patients with and without spontaneous ascites infection

Background and Aim:  Spontaneous ascites infection is a frequently encountered and important complication of decompensated liver cirrhosis. The immune system plays an important role in the development or eradication of this infection. A number of compositional and functional alterations in immune system cells have been demonstrated in cirrhotic patients; however, there is a lack of knowledge about this issue in ascitic infections. The aim of the present study was to evaluate lymphocyte subsets and levels of some ascitic and lymphocytic intracytoplasmic cytokines in decompensated cirrhotic patients with or without spontaneous ascites infection.

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.

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 Uludağ 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.

Treatment of advanced classic Kaposi's sarcoma with weekly low‐dose paclitaxel therapy

Treatment of advanced classic Kaposi’s sarcoma with weekly low-dose paclitaxel therapy Several reports have been published recently documenting the efficacy of paclitaxel monotherapy in human immunodeficiency virus (HIV)-associated and post-transplant Kaposi’s sarcoma (KS). The standard dosing and frequency of this therapy has not yet been established, however. We present here an interesting case of classic KS with gastrointestinal involvement and human herpesvirus-8 (HHV-8) positivity responding to weekly low-dose paclitaxel monotherapy, suggesting a tolerable and alternative regimen in the elderly. A 76-year-old woman presented with multiple reddish-blue plaques and nodules of 7 years’ duration distributed widely on the distal upper and lower extremities and face (Fig. 1). Oral examination revealed a reddish-blue plaque, 1.5 cm in size, on the hard palate. No lymphadenopathy or organomegaly was detected by systemic examination. The histopathologic examination of the punch biopsy specimen was compatible with KS (Fig. 2). The patient was HIV negative, but HHV-8 was found to be positive in blood on polymerase chain reaction (PCR) analysis. Systemic evaluation of the patient revealed anemia (hemoglobin, 7.3 g/dL) and occult blood testing was positive. In addition to chronic gastritis, endoscopic examination demonstrated two similar nodules on the descending part of the duodenum which were confirmed histopathologically as KS. Computed tomographic examination of the thorax and abdomen did not show any metastatic lesion or lymphadenopathy. As a result of gastrointestinal involvement and widespread distribution of the lesions, weekly low-dose paclitaxel chemotherapy (60 mg/m in 250 mL of normal saline solution) was initiated. Because of this drug’s marked allergenicity, the patient was premedicated by the infusion of 40 mg dexamethasone intravenously 30 min prior to the paclitaxel infusion. Ten courses were administered. After eight courses of therapy, all lesions, including those on the oral mucosa, had dramatically regressed. The side-effects observed during therapy were alopecia and granulocytopenia. The patient received a total of 10 injections of granulocyte-colony stimulating factor during therapy. She experienced myalgia once after the first course of therapy. At the end of 10 courses, the skin lesions had improved with postinflammatory hyperpigmentation (Fig. 3). Endoscopic examination revealed the disappearance of duodenal lesions. A punch biopsy from the hyperpigmented macules showed no residual disease except for a few ecstatic blood vessels. The patient has been followed up for 15 weeks with no recurrence. The disseminated skin lesions and presence of duodenal involvement in this case warranted the application of chemotherapy as the best approach. Systemic medications that are Food and Drug Administration (FDA) approved are liposomal doxorubicin, paclitaxel, and interferon-α. As a result of previous experience demonstrating its efficacy as a single agent in KS, paclitaxel was preferred. Paclitaxel exerts its antitumor effects by several mechanisms, most importantly by the polymerization of microtubules, inhibition of cell division, and induction of cell death, possibly by the down-regulation of bcl-2 expression. Paclitaxel was

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.

Acute myocardial infarction, ischemic cerebrovascular disease and variceal bleeding due to portal vein thrombosis in a patient with hereditary thrombophilia.

We report on a 43-year-old female patient with multiple thrombotic risk factors who, in a few months, developed acute myocardial infarction, an ischemic cerebrovascular event and variceal bleeding due to portal vein thrombosis. The factor V Leiden mutation was carried in heterozygous form, homocysteine was elevated at 19.6 micromol/l, and methylenetetrahydrofolate reductase C677T mutation was carried in homozygous form. Moderately increased plasma homocysteine level and a reduced protein S activity were evident. Anticardiolipin IgG antibodies were mildly positive. We conclude that the presence of multiple genetic and environmental risk factors greatly amplifies the risk of clinical thrombotic events.

Sağ Kolon Yerleşimli Adenomlar: High-Grade Displazi veya İnvaziv Kanser için Risk Faktörü

Amac: Bu calismanin amaci high-grade displazi (HGD) ve invaziv kanser ( “ilerlemis patoloji (IP)” olarak tanimlanmistir) ile iliskili multipl hasta ve adenom karakterlerini degerlendirmektir. Materyal ve Metod: Toplam 6250 islem sonunda 894 hastada 1379 (% 22.06) polip mevcuttur. Biz patoloji sonuclarina ulasabildigimiz 914 polipi degerlendirmeye aldik. Bulgular: 914 polipte toplam 699 adenom tespit edildi. A total of 699 adenomas were detected from 914 polyps. Sag kolon yerlesimli poliplerde sola gore daha yuksek oranda IP ozellikleri bulundu (% 18.5 vs % 7.1 p: 0.002). Lojistik regresyon analizi sonucunda; erkek cinsiyet, 2 cm’e esit ya da buyuk boyut, villoz histoloji ve non-dimunitif gorunum adenomlardaki IP ozellikleri icin bagimsiz risk faktorleri olarak bulundu. Sonuc: Calismamizda, diger calismalara benzer olarak, erkek cinsiyet, 2 cm’e esit ya da buyuk boyut, villoz histoloji ve non-dimunitif gorunum adenomlardaki IP ozellikleri icin bagimsiz risk faktorleri olarak bulundu. Fakat diger bircok calismanin aksine biz sag kolon yerlesimli poliplerde sol taraf yerlesimli poliplere gore daha yuksek oranda IP ozellikleri bulduk.The long QT syndrome (LQTS) is characterized with arrhythmic attacks, repeating syncopes,seizures, and ventricular arrhythmias leading to sudden death. Arrhythmias with a potential ofmortal course develop due to elongation of ventricular repolarization, either acquired or inborn.Herein the present paper, a case of congenital LQTS, admitted after a sudden cardiac arrest andtotally recovered with implantable cardiac defibrillator (ICD), was focused on

Right-Sided Adenomas of the Colon: A Risk Factor For High-Grade Dysplasia or Invasive Cancer

Amac: Bu calismanin amaci high-grade displazi (HGD) ve invaziv kanser ( “ilerlemis patoloji (IP)” olarak tanimlanmistir) ile iliskili multipl hasta ve adenom karakterlerini degerlendirmektir. Materyal ve Metod: Toplam 6250 islem sonunda 894 hastada 1379 (% 22.06) polip mevcuttur. Biz patoloji sonuclarina ulasabildigimiz 914 polipi degerlendirmeye aldik. Bulgular: 914 polipte toplam 699 adenom tespit edildi. A total of 699 adenomas were detected from 914 polyps. Sag kolon yerlesimli poliplerde sola gore daha yuksek oranda IP ozellikleri bulundu (% 18.5 vs % 7.1 p: 0.002). Lojistik regresyon analizi sonucunda; erkek cinsiyet, 2 cm’e esit ya da buyuk boyut, villoz histoloji ve non-dimunitif gorunum adenomlardaki IP ozellikleri icin bagimsiz risk faktorleri olarak bulundu. Sonuc: Calismamizda, diger calismalara benzer olarak, erkek cinsiyet, 2 cm’e esit ya da buyuk boyut, villoz histoloji ve non-dimunitif gorunum adenomlardaki IP ozellikleri icin bagimsiz risk faktorleri olarak bulundu. Fakat diger bircok calismanin aksine biz sag kolon yerlesimli poliplerde sol taraf yerlesimli poliplere gore daha yuksek oranda IP ozellikleri bulduk.The long QT syndrome (LQTS) is characterized with arrhythmic attacks, repeating syncopes,seizures, and ventricular arrhythmias leading to sudden death. Arrhythmias with a potential ofmortal course develop due to elongation of ventricular repolarization, either acquired or inborn.Herein the present paper, a case of congenital LQTS, admitted after a sudden cardiac arrest andtotally recovered with implantable cardiac defibrillator (ICD), was focused on