Murat Taner Gulsen

Long-term Efficacy and Safety of Lamivudine, Entecavir, and Tenofovir for Treatment of Hepatitis B Virus–Related Cirrhosis

BACKGROUND & AIMS Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.

The radio-protective effects of caffeic acid phenethyl ester and thymoquinone in rats exposed to total head irradiation.

SummaryBackgroundMany cancer patients treated with radiotherapy suffer severe side effects during and after their treatment. The aim of this study was to investigate the effects of irradiation and the addition of caffeic acid phenethyl ester (CAPE) and thymoquinone (TQ) on the oxidant/antioxidant system in the liver tissue of irradiated rats.MethodsA total of 40 Sprague–Dawley rats were divided into five groups to test the radioprotective effectiveness of thymoquinone and caffeic acid phenethyl ester administered by intraperitoneal injection. Appropriate control groups were also studied.ResultsWhile liver tissue total oxidant status, lipid hydroperoxide level, and oxidative stress index were significantly increased in the irradiated (IR) group, compared with other groups, total antioxidant status, sulfhydryl levels, and paraoxonase (PON) activity were significantly decreased. Ceruloplasmin activity in IR plus TQ and IR groups was higher than the control group. Arylesterase and PON activities in IR plus TQ- and IR plus CAPE-supplemented groups were lower than those of control groups.ConclusionsTQ and CAPE decrease oxidative stress markers and have antioxidant effects, which also augment antioxidant capacity in the liver tissue of irradiated rats.ZusammenfassungGrundlagenViele Krebspatienten, die mit Bestrahlung behandelt werden, leiden unter schweren Nebenwirkungen während und nach der Behandlung. Ziel dieser Studie war es, die Wirkung einer Bestrahlung und die Zugabe von Kaffeesäurephenylethylester (KAPE) und Thymoquinon (TQ) auf das Oxidant/Antioxidant System im Lebergewebe von Ratten zu untersuchen.MethodikVierzig Sprague-Dawley Ratten wurden in 5 Gruppen eingeteilt, um die radioprotektive Wirkung von intraperitoneal verabreichtem TQ und KAPE zu untersuchen. Entsprechende Kontrollgruppen wurden auch untersucht.ErgebnisseDer Gesamt oxidative Status (TOS), die Konzentrationen von Lipid Hydroperoxid (LOOH) und der oxidative Stress Index des Lebergewebes waren in der IR (= bestrahlte) Gruppe im Vergleich zu den anderen Gruppen signifikant erhöht. Der Gesamt antioxidative Status (TAS), die Konzentrationen von Sulfhydryl (–SH) und Paraoxonase (PON) waren im Gegensatz dazu signifikant erniedrigt. Die Cp Aktivität waren in der IR plus TQ, sowie in der IR Gruppe höher als in der Kontrollgruppe. ARYL und PON Aktivitäten waren in der IR Gruppe mit TQ und der Gruppe mit KAPE niedriger als bei den Kontrollgruppen.SchlussfolgerungenTQ und KAPE senken die Marker des oxidativen Stresses und haben eine antioxidative Wirkung. Dadurch wird die antioxidative Kapazität im Lebergewebe von bestrahlten Ratten erhöht.

Drug-induced esophageal ulcers: case series and the review of the literature.

BACKGROUNDS/AIMS Drugs can cause several complications in the esophagus and lead to pill esophagitis. In this paper, our purpose is to share our clinical experience in light of the literature and put forward the general characteristics of pill esophagitis. MATERIALS AND METHODS In our clinic, between January 2008 and June 2012, by excluding other factors, 48 patients were included in the study, diagnosed as drug-induced esophagitis with their history, endoscopic view, and histopathologic evaluation. RESULTS There were 34 (70.9%) female and 14 (29.1%) male patients in the study, and their average ages were 35.1 and 32.4, respectively. Clinical symptoms were odynophagia (79.1%), retrosternal pain (62.5%), and dysphagia (47.9%). The reason for these symptoms for 85.5% of the patients was related to insufficient water consumption while taking the pill, taking the pill in recumbent position, or both. Tetracycline and its variant, doxycycline, were responsible for 52% of the patients, and 62.5% of the drugs were in capsule form. Ulcers were at the proximal and middle third of the esophagus in 79.2% of the patients. In the histopathologic evaluation, nonspecific acute inflammatory changes were found in 29.1% of the cases. Various proton pump inhibitors and sucralfate were used in the treatment. While no perforation and structure were detected, 1 patient died because of repetitive arterial bleeding. CONCLUSION Almost every kind of drug, particularly doxycycline, can cause ulcer in the esophagus. Pill esophagitis can be prevented by warning patients about drinking water sufficiently and sitting up while taking the pill.

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.

Study of ideal topical pharyngeal anesthesia in upper gastrointestinal system endoscopy: A double-blind, randomized, controlled trial

BACKGROUND/AIMS This study is designed to determine which drug forms provide ideal pharyngeal anesthesia when used during upper gastrointestinal system endoscopy. MATERIALS AND METHODS A total of 180 patients were included in the study. Using the random number table, these patients were divided into three groups. Group 1, lidocaine gel+isotonic spray; Group 2, base lubricant gel+lidocaine spray; and Group 3: lidocaine gel+lidocaine spray. Data were collected from the patient identification form, compliance to operation form, and State Anxiety Inventory. RESULTS Anesthetization and compliance to procedure scores were higher and anxiety scores were lower in Group 3 than in other groups (p<0.05). It was observed that as the compliance score increased, the anesthetization and satisfaction scores also increased; however, coughing during the procedure, duration of the procedure, and anxiety scores decreased (p<0.05). It was determined that as anesthetization scores increased, discomfort in the throat caused by the device, coughing during the procedure, and anxiety scores decreased (p<0.05). CONCLUSION Lidocaine gel and spray combination is the most ideal pharyngeal anesthesia to ensure the adaptation of the patient to the procedure and to decrease anxiety and discomfort during the procedure.

Lamivudine Treatment Failure Risks in Chronic Hepatitis B Patients with Low Viral Load

Aim: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL). Material and Methods: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <109 copies/ml and for HBeAg- patients HBV DNA <107 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. Results: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥100,000 copies/ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). Conclusion: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Assessment of histopathological alterations in patients with chronic hepatitis B infection following long-term oral antiviral therapy

Objectives: To evaluate the histopathological changes in the liver after oral antiviral therapy in patients with chronic hepatitis B. Methods: A total of 79 HBeAg-negative and positive patients who had been on lamivudine, entecavir, or tenofovir disoproxil for at least 3 years prior to inclusion were enrolled between March 2015 and 2016, retrospectively. There were 23 patients on lamivudine, 21 patients on entecavir, and 35 on tenofovir. All patients underwent a follow-up liver biopsy. Biochemical, serological, virological and histopathological data were recorded in all patients and were compared after at least 3 years of treatment with oral antiviral agents. Results: Histological activity index scores were reduced in patients who received lamivudine (p=0.011), entecavir (p=0.002), and tenofovir (p=0.001). Also, in contrast with a significant improvement in fibrosis scores in lamivudine (p=0.033) and tenofovir (p=0.001) groups no improvements were found in patients who received entecavir (p=0.090). Conclusion: Long term treatment with oral antiviral agents was associated with biochemical, virological, serological, and histopathological improvements. Long-term use of anti-viral agents as well as continuous suppression of HBV DNA are prerequisites for histopathological improvement.

The Radio-protective Effects of Caffeic Acid Phenethyl Ester and Thymoquinone on Oxidative and Nitrosative Stress in Liver Tissue of Rats Exposed to Total Head Irradiation.

Objective The aim of this study is to investigate the effects of addition of caffeic acid phenethyl ester (CAPE) and thymoquinone (TQ) on oxidative and nitrosative stress in the liver tissue of irradiated rats. Methods Forty Sprague-Dawley rats were divided into five groups to test the radioprotective effectiveness of TQ and CAPE administered by intraperitoneal injection. Appropriate control groups were also studied. Results Liver antioxidant capacity, as measured by levels of total superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA) and glutathione-S-transferase (GST) activity except superoxide dismutase (SOD) activity, were statistically lower in the irradiation (IR) group compared to all other groups. Total superoxide scavenger activity and NSSA were statistically higher in the IR plus TQ and IR plus CAPE groups compared to all other groups. In contrast, glutathione peroxidase (GSH-Px) activity was significantly found to increase in the IR plus CAPE group compared to control groups. The xanthine oxidase (XO), nitric oxide synthase (NOS) activities, nitric oxide (NO●) and malondialdehyde (MDA) levels in the IR group were statistically higher than in the other groups. Moreover, XO activity in the IR plus TQ group was statistically lower than all other groups including the IR plus CAPE group. In addition, NO● level was found to increase in all groups when compared to the normal control group. Conclusions Thymoquinone and CAPE decrease oxidative and nitrosative stress markers and have antioxidant effects, which also increase antioxidant capacity in the liver tissue of irradiated rats.

Malignant duodenocolic fistula diagnosed by endoscopy.

A 69-year-old man was admitted to the hospital complaining of diarrhoea, abdominal pain, foul-smelling vomiting for 2 days. Physical examination revealed a soft non-distended abdomen, dehydration, anaemia, cachexia. Biochemical examinations were within normal limits. Endoscopic examination showed a large necrotic ostium of mass involving the bulbus (Figure 1). When endoscope passed through the ostium via fistula, the colonic mucosa appeared. Lower endoscopy performed in the same day revealed that the fistula was between back wall of the bulbus and the level of the hepatic flexure (Figure 2). Colonic biopsy revealed a poorly differentiated mucinous adenocarcinoma. The patient urgently underwent surgery. Surgical exploration revealed the tumor extending through the hepatic flexure of the colon into the bulbus. He was operated on right hemicolectomy combined with a Whipple procedure. The patient died 4 months later.