Mehmet Koruk

Mutations in the S gene region of hepatitis B virus genotype D in Turkish patients

The S gene region of the hepatitis B virus (HBV) is responsible for the expression of surface antigens and includes the ‘a’-determinant region. Thus, mutation(s) in this region would afford HBV variants a distinct survival advantage, permitting the mutant virus to escape from the immune system. The aim of this study was to search for mutations of the S gene region in different patient groups infected with genotype D variants of HBV, and to analyse the biological significance of these mutations. Moreover, we investigated S gene mutation inductance among family members. Forty HBV-DNA-positive patients were determined among 132 hepatitis B surface antigen (HbsAg) carriers by the first stage of seminested PCR. Genotypes and subtypes were established by sequencing of the amplified S gene regions. Variants were compared with original sequences of these serotypes, and mutations were identified. All variants were designated as genotype D and subtype ayw3. Ten kinds of point mutations were identified within the S region. The highest rates of mutation were found in chronic hepatitis patients and their family members. The amino acid mutations 125 (M → T) and 127 (T → P) were found on the first loop of ‘a’-determinant. The other consequence was mutation inductance in a family member. We found some mutations in the S gene region known to be stable and observed that some of these mutations affected S gene expression.

Effect of Vitamin A against Methotrexate-Induced Damage to the Small Intestine in Rats

Objective: The aim of the present study was to examine whether or not the administration of vitamin A (VA) protects against methotrexate (MTX)-induced damage to small intestinal epithelium. Materials and Methods: Sixty-three male Wistar albino rats, 10–12 weeks old, weighing 240–280 g, were divided into three groups: (1) controls, (2) rats receiving MTX treatment alone, and (3) rats receiving MTX plus VA treatment. A single dose of MTX (20 mg/kg MTX in 20 ml vehicle) was administered to the rats intraperitoneally. For MTX plus VA treated groups, retinol palmitate (VA) 5,000 IU/kg dissolved in 0.5 ml sunflower oil was administered by intragastric tube 3 days prior to MTX treatment and continued till the rats were sacrificed. The control group was treated with vehicle. Both control and MTX-alone groups were also treated with sunflower oil as a placebo. The rats were sacrificed on the 2nd, 4th and 6th day after MTX treatment. Tissue samples from the jejunum were taken for histopathological analysis. Results: MTX treatment induced villus shortening and fusion, epithelial atrophy, crypt loss, inflammatory infiltrate in the lamina propria, and goblet cell depletion. The pre- and post-treatment administration of VA decreased the severity of jejunal damage caused by MTX treatment. Conclusion: Our results confirmed that administration of VA decreased the MTX-induced damage to the small intestine. This protective effect of VA may have clinical applications in cancer chemotherapy.

Colon carcinoma with synchronous subcutaneous and osseous metastasis: a case report.

Colon cancer usually metastasizes initially to regional lymphatics and later through the bloodstream. Hematogenous metastasis usually includes the liver, lungs, and brain. In colorectal cancer, osseous and/or subcutaneous metastasis without liver metastasis is a very uncommon event. We present here a case of colon adenocarcinoma, which synchronously metastasized to facial and other subcutaneous tissue and to bone within a short period after definitive therapy. Although such a pattern is uncommon, diagnostic biopsy for any new or suspicious lesion of the skin and bone scintigraphy for symptomatic patients should be done for patients with a colorectal cancer history.

Granulocytic sarcoma of the colon and leukemic infiltration of the liver in a patient presenting with hematochezia and jaundice.

Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome, chronic myelogenous leukemia, or acute myelogenous leukemia (AML). Involvement of the gastrointestinal tract is relatively rare in GS. We present an extremely rare case of GS of the colon and liver infiltration in a 60-year-old male patient with AML presenting with jaundice and hematochezia and review the literature. It should be kept in mind that hematochezia may be due to colonic involvement of GS besides thrombocytopenia which is usually encountered in patients with AML.

The efficacy, safety and tolerability of pantoprazole-based one-week triple therapy in H. pylori eradication and duodenal ulcer healing

SUMMARY Objective: Recently, proton pump inhibitor (PPi)-based triple therapy has been recommended as a first line treatment in the eradication of Helicobacter pylori. The aim of this open, multicentre trial was to investigate the efficacy, safety, tolerability and the ulcer healing rate of a triple regimen consisting of pantoprazole∗ 40 mg, clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 7 days, in the eradication of H. pylori in patients with duodenal ulcer in Turkey. Research design and methods: H. pylori infection was assessed by histological examination and rapid urease test at baseline and 4 weeks after the completion of the therapy. Seventy-seven patients were enrolled, 5 were excluded due to various reasons and 72 completed the entire course of the trial. Results: H. pylori eradication was confirmed in 49 of these patients; the eradication rate was 68% by per-protocol analysis and 63.6% by intention-to-treat analysis. The ulcers were completely healed in 61 patients (85%) at the second endoscopic examination. Drug compliance was excellent (97.3%) and there were no serious adverse events. Conclusion: Pantoprazole-based 1-week triple therapy was well tolerated and the ulcer healing rate was high (85%). Relatively low H. pylori eradication rates may be attributed to rising antibiotic resistance over recent years. A large scale, comparative study with other PPi-based regimens is warranted based on the results of this open study with the pantoprazole-based regimen.

High Prevalence of Transfusion-Transmitted Virus Infection in Patients with Chronic Liver Diseases in an Endemic Area of Hepatitis B and C Virus

Objective: To determine the prevalence and clinical impact of transfusion-transmitted virus (TTV) DNA in patients with chronic liver diseases in the Southeast Anatolia region of Turkey where hepatitis B and C viral infections are endemic. Subjects and Methods: Patients diagnosed with chronic liver disease by clinical, biochemical and histologic means were enrolled in the study. Serum samples of 60 patients (19 males, 41 females) with chronic liver diseases, and of 45 healthy volunteer blood donors as a control group were collected. The chronic liver disease group consisted of 11 patients with hepatitis B, 44 with hepatitis C and 5 with chronic liver disease of unknown etiology. Presence of TTV DNA was investigated by the polymerase chain reaction. Using a scoring system histological grading of inflammation and staging of fibrosis were performed only in the chronic hepatitis C group. Results: TTV DNA was detected in 47 (78%) patients with chronic liver disease and 5 (11%) volunteers in the control group. The difference was statistically significant (p < 0.001). Ten of the 11 (91%) patients with hepatitis B, 32 of 44 (73%) of those with hepatitis C-related chronic liver disease, and 5 of 5 (100%) of the patients with cryptogenic liver disease were positive for TTV DNA. Conclusion: TTV is highly prevalent in patients with chronic liver diseases in Southeast Anatolia, Turkey but no pathogenic effect attributable to TTV infection was detected.

Drug- and herb-induced liver injury: a case series from a single center.

BACKGROUND/AIMS Drug-induced liver injury (DILI) is common worldwide and has a potentially fatal outcome. It accounts for more than half of the cases of acute liver failure in the United States. Herb-induced liver injury (HILI) is a less documented condition but a growing problem. We present here the clinical characteristics and outcome of patients with drug- and herb-induced liver injury from our center. MATERIALS AND METHODS In this 4-year retrospective study, 82 patients in whom there was a causal or highly probable relationship between herbal medicine or drug use and liver disease are presented. RESULTS The mean age of patients was 43.1±14.8 years; sexual distribution was 53 females and 29 males. The major cause of hepatotoxicity was drugs (87.8%), with herbal medicine accounting for 12.2%. The leading causative agents were nonsteroidal anti-inflammatory drugs (NSAIDs) (23.1%), followed by antibiotics (19.5%). The pattern of hepatotoxicity was hepatocellular in 35 patients (42.6%), mixed in 28 (34.1%), and cholestatic in 19 patients (23.1%). Teucrium polium (known popularly as felty germander), which is a traditionally used herbal medicine of the Labiatae family in our region, was the most common cause of herb-induced liver injury and responsible in 7 of 10 herbal hepatotoxic cases. Acute liver failure developed in 3 patients (two patients related with flurbiprofen and diclofenac and one patient due to an isoniazid-rifampicin combination). CONCLUSION Antibiotics and NSAIDs were the most common etiologic agents for drug-induced liver injury. Surprisingly, herbs follow these groups of drugs and must be questioned more carefully.

Effects of interferon-alpha therapy on cardiac function in patients with chronic hepatitis B infection.

Various types of cardiovascular complications, such as myocardial infarction, cardiac arrhythmias, cardiomyopathy, and myocarditis attributed to interferon therapy have been reported. The aim of this study was to evaluate the cardiac effects of interferon-α (IFN-α) in patients with chronic hepatitis B infection. Forty-five patients with chronic hepatitis B infection (41 men and 3 women; mean age 34.2 ± 11.5 years) were included in the study, and 10 MU IFN-α 2b was administered three times a week for 6 months to the patients. Cardiac evaluation (detailed medical history, physical examination, electrocardiography, systolic and diastolic function parameters by echocardiography) was performed at the beginning, and at the 1st, 3rd, and 6th months of therapy. No patients had any cardiac symptoms during interferon therapy, and systolic and diastolic blood pressure and heart rate were not significantly affected (P > 0.05). None of the patients revealed cardiac rhythm disturbance on electrocardiography before or during the therapy period. No significant changes were detected in systolic (ejection fraction, fractional shortening, pre-ejection period, left ventricular ejection time, the ratio of pre-ejection period/ejection time, Q-V peak) and diastolic (E peak, A peak of transmitral flow velocity, E/A ratio, deceleration time, isovolumic relaxation time by conventional echocardiography, and E peak, A peak, deceleration time of E wave at the medial and lateral corners of the mitral annulus by tissue Doppler echocardiography) left ventricular function parameters between the beginning and the 1st, 3rd, and 6th months of therapy. The results of this study suggest that IFN-α therapy does not cause a significant deterioration in cardiac function in patients with chronic hepatitis B infection, and it may be used safely in patients without cardiac disease.

Gastrocolic fistula secondary to gastric diffuse large B-cell lymphoma in a patient with pulmonary tuberculosis.

Gastrocolic fistula secondary to primary gastric lymphoma is a very rare entity. On admission to outpatient clinics, it may be difficult to diagnose gastrocolic fistula, as its clinical symptoms are nonspecific. A 65-year-old man was presented with weight loss, nausea, vomiting, diarrhea, fatigue, foul-smelling eructation, and upper abdominal pain for the last 2 months. He had also been started antituberculosis drugs 2 months ago because of acid-resistant bacillus (ARB) positivity in sputum in a state hospital. Therefore, symptoms such as nausea and vomiting were attributed to the drugs used for tuberculosis. However, nausea and vomiting continued despite stopping the drugs. Upper endoscopical examination revealed a large crater on the posterior wall of gastric corpus. A large fistulous opening to the transverse colon was also identified during endoscopic examination. An upper gastrointestinal x-ray series demonstrated a fistula between the stomach and the transverse colon. Histopathological examination of the gastric biopsy was determined to be primary gastric diffuse large B-cell-type non-Hodgkins lymphoma. In conclusion, persistent vomiting may suggest a probable gastrocolic fistula despite nonspecific clinical findings. In the literature, the present case represents the first report of a gastrocolic fistula due to gastric lymphoma in a patient with tuberculosis at its initial presentation.

Demographic and Clinicopathological Characteristics of Nonalcoholic Fatty Liver Disease in the East-Southeastern Anatolia Regions in Turkey

Objective: To identify the demographic and clinicopathological characteristics of patients diagnosed with nonalcoholic fatty liver disease (NAFLD) and the risk factors for fibrosis based on histopathological findings in East-Southeastern Anatolia regions in Turkey. Subjects and Methods: The study included a total of 93 patients diagnosed with NAFLD from 5 different centers. Histopathological findings were evaluated by dividing them into four categories using Matteoni classifications. Cases with fibrosis were further evaluated using Brunt classifications. Results: The patients with a nonalcoholic fatty liver were in the 3rd and 4th decade age groups. The mean age was 38 years, 76% of the patients were male, 85% were overweight, 37% were obese, 18% had type 2 diabetes mellitus, and 80.6% had hyperlipidemia. A multiple regression analysis showed that age, type 2 diabetes mellitus, and aspartate aminotransferase (AST) levels were linked with the severity of the disease. Of the 93 patients, 55 (59.1%) had fibrosis, of which 10.8% were classified as severe. The severity of fibrosis was significantly higher in obese patients. Conclusions: The risk factors for severity of NAFLD included advanced age, type 2 diabetes mellitus and serum AST level, while the risk factor for the severity of fibrosis was obesity.