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.

Effect of prior hepatitis B virus exposure on long-term risk of liver-related events after liver transplantation.

OBJECTIVE: To characterize the risk of liver-related events and death in hepatitis B virus (HBV)-exposed liver transplantation (LT) recipients. METHODS: Retrospective review was performed in all adults who underwent LT between January 1995 through December 2010 at the Johns Hopkins Hospital. Recipients with graft failure or death within 14 d of LT or missing HBV status were excluded, leaving 575 individuals for analysis. Patients were classified according to HBV exposure status: Unexposed, Resolved HBV, Chronic HBV, or hepatitis B core antibody (anti-HBc) seropositive liver donor. RESULTS: Compared with HBV-unexposed patients, the relative hazard of combined liver-related events (rejection, cirrhosis, re-transplantation) and death after LT was not increased in patients with a baseline history of resolved HBV infection or chronic hepatitis B. Using anti-HBc seropositive donors also did not increase the risk of liver-related events, death, or composite events (all p ≥ 0.05). However, hepatitis C was associated with liver-related events [adjusted hazard ratio (aHR), 1.59; 95% confidence interval (CI), 1.00-2.52], and blacks had a higher risk of death (aHR, 1.50; 95% CI, 1.01-2.22). CONCLUSION: LT of patients with prior HBV exposure or use of anti-HBc seropositive donors is not associated with increased risk of liver-related events or death.

Sirolimus based immunosuppression is associated with need for early repeat therapeutic ERCP in liver transplant patients with anastomotic biliary stricture.

INTRODUCTION: Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). MATERIAL AND METHODS: Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. RESULTS: 45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038). CONCLUSIONS: Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.

HTK preservative solution is associated with increased biliary complications among patients receiving DCD liver transplants: a single center experience.

BACKGROUND: This study compares biliary complication rates associated with use of two different preservative solutions, Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW), utilized in orthotopic liver transplantation (LT) with donations after cardiac death (DCDs). MATERIAL AND METHODS: Between 1997-2010, we retrospectively studied 35 LTs performed utilizing DCD donors, preserved either with HTK (n=17) or UW(n=18). Biliary complications were defined by the presence of anastomotic strictures, non-anastomotic strictures, and/or biliary leak on endoscopic retrograde cholangiopancreatography. RESULTS: HTK and UW cohorts were similar in terms of demographics as well as pre- and post-operative biochemical profile. Donor age was significantly higher among HTK compared to UW recipients (41.5 ± 11.9 vs. 26.2 ± 8.8 years, p<0.001). The incidence of post-LT biliary complications was higher in the HTK group (76% vs. 39% in UW group, p=0.041). Hepatic arterial thrombosis (HAT) was observed among 3 HTK patients (17.7%) and 1 UW patient (5.6%), p=0.33. No patients underwent retransplantation in UW group, five recipients in HTK group underwent retransplantation (29%), p=0.019; 4 due to biliary complications and 1 due to HAT. CONCLUSIONS: This single-center study reveals that the use of HTK preservative among DCD donors is associated with an increased risk of biliary complications. Multicenter retrospective studies are suggested to further verify this observation.

Therapeutic effect of caffeic acid phenethyl ester on cerulein-induced acute pancreatitis.

AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of cerulean-induced acute pancreatitis (AP). METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 microg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-alpha levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased significantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathological results and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-alpha concentration was nearly the same in the CAPE and placebo groups. CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of beneficial effects of CAPE before clinical usage of this agent.

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-Hodgkin's 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.

Leptin levels in the differential diagnosis between benign and malignant ascites.

AIM: To evaluate the role of leptin levels in the differential diagnosis of ascites. METHODS: Ascitic leptin, TNFalpha and serum leptin levels were measured in 77 patients with ascites (35 with malignancies, 30 cirrhosis and 12 tuberculosis). Control serum samples were obtained from 20 healthy subjects. Leptin and TNFalpha levels were measured by ELISA. Body mass index (BMI) and percentage of body fat (BFM) by skin fold measurement were calculated for all patients and control groups. Peritoneal biopsy, ascites cytology and cultures or biochemical values were used for the diagnosis of patients. RESULTS: In patients with malignancies, the mean serum and ascites leptin levels and their ratios were significantly decreased compared to the other patient groups and controls. In tuberculosis peritonitis, ascitic fluid TNFalpha levels were significantly higher than malignant ascites and cirrhotic sterile ascites. BMI and BFM values did not distinguish between patients and controls. CONCLUSION: In patients with malignant ascites, levels of leptin and TNFalpha were significantly lower than in patients with tuberculous ascites.

Listening to Turkish classical music decreases patients' anxiety, pain, dissatisfaction and the dose of sedative and analgesic drugs during colonoscopy: a prospective randomized controlled trial.

AIM: To determine whether listening to music decreases the requirement for dosages of sedative drugs, patients' anxiety, pain and dissatisfaction feelings during colonoscopy and makes the procedure more comfortable and acceptable. METHODS: Patients undergoing elective colonoscopy between October 2005 and February 2006 were randomized into either listening to music (Group 1, n = 30) or not listening to music (Group 2, n = 30). Anxiolytic and analgesic drugs (intravenous midazolam and meperidine) were given according to the patients' demand. Administered medications were monitored. We determined their levels of anxiety using the State-Trait Anxiety Inventory Test form. Patients' satisfaction, pain, and willingness to undergo a repeated procedure were self-assessed using a visual analog scale. RESULTS: The mean dose of sedative and analgesic drugs used in group 1 (midazolam: 2.1 +/- 1.4, meperidine: 18.1 +/- 11.7) was smaller than group 2 (midazolam: 2.4 +/- 1.0, meperidine: 20.6 +/- 11.5), but without a significant difference (P > 0.05). The mean anxiety level in group 1 was lower than group 2 (36.7 +/- 2.2 vs 251.0 +/- 1.9, P < 0.001). The mean satisfaction score was higher in group 1 compared to group 2 (87.8 +/- 3.1 vs 58.1 +/- 3.4, P < 0.001). The mean pain score in group 1 was lower than group 2 (74.1 +/- 4.7 vs 39.0 +/- 3.9, P < 0.001). CONCLUSION: Listening to music during colonoscopy helps reduce the dose of sedative medications, as well as patients' anxiety, pain, dissatisfaction during the procedure. Therefore, we believe that listening to music can play an adjunctive role to sedation in colonoscopy. It is a simple, inexpensive way to improve patients' comfort during the procedure.

An interesting cause of esophageal ulcer etiology: Multiple myeloma of IgG kappa subtype.

Multiple myeloma is a neoplasm of mature and immature plasma cells. A 50-year-old woman with lumbago, dysphagia, and left arm pain was presented. Upper endoscopical examination was performed. There was an exudate-covered ulcer in the distal esophagus, located at 30-32 cm from the incisors, covering the whole mucosa. Histopathological examination of the specimens obtained from the lesion showed the involvement of plasma cells consistent with multiple myeloma of IgG kappa subtype. Esophageal involvement of multiple myeloma should be kept in mind in patients presenting with dysphagia.