Interferon Treatment Duration in Patients With Chronic Delta Hepatitis and its Effect on the Natural Course of the Disease.

Background: Interferon is the only treatment option in chronic delta hepatitis (CDH). A CDH database (333 patients, 161 with interferon treatment history) was analyzed for effects of treatment duration on virologic response and clinical outcomes. Methods: Ninety-nine CDH patients who received at least 6 months of interferon were selected. Maintained virologic response (MVR) was defined as hepatitis D virus RNA negative for 2 years after treatment discontinuation. Cumulative median interferon treatment duration was 24 months (range 6-126 months), with a median of 2 courses (range 1-8). Post-treatment median follow-up was 55 months (24-225 months). Results: Thirty-five patients achieved MVR. Cumulative probability of MVR increased with treatment duration and reached 50% at 5 years. Patients with MVR were less likely to die from liver disease or develop complications compared to patients without MVR (P = .032, P = .006, respectively). Cirrhosis at baseline and no response to therapy (odds ratio 16.1 and 5.23, respectively) predicted an adverse endpoint. Hepatitis B surface antigen clearance occurred in 37% of patients with MVR. Conclusion: Viral response to interferon increases with treatment duration and favorably affects the natural course of disease. Interferon treatment duration has to be individualized with careful post-treatment assessment.

Entecavir treatment of chronic hepatitis D.

BACKGROUND: Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD). METHODS: This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment. RESULTS: Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log(10) copies/mL ± .70 vs 4.68 ± .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment. CONCLUSIONS: One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.

Incidence of acute hepatitis B in patients with spinal cord injury.

STUDY DESIGN: Retrospective case survey. OBJECTIVE: To examine incidence and clinical characteristics of hepatitis B infection in individuals with spinal cord injury (SCI). SETTING: Inpatient clinic within a physical medicine and rehabilitation hospital specialized in rehabilitation. PARTICIPANTS: A total of 161 patients with SCI. INTERVENTIONS: Patients' records were investigated and the status of hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), anti-hepatitis B surface antigen positivity, alanine aminotransferase levels, duration of hospitalization and cost were recorded. MAIN OUTCOME MEASURES: Incidence of acute hepatitis B. RESULTS: Six patients were diagnosed with acute hepatitis B on the first hospitalization for rehabilitation. A total of 11 patients (4.2%) were HBsAg positive with a previously established diagnosis of hepatitis B virus infection, 1 patient (0.4%) was anti-HCV positive. After a follow-up of 6 months, three of the acute hepatitis B patients progressed into chronic hepatitis B stage. In acute hepatitis B patients' initiation of the rehabilitation was delayed, duration of hospitalization was increased. CONCLUSIONS: After SCI, patients are at high risk of acute hepatitis B infection. A high rate of chronicity may be associated with impaired immune response, secondary to neurological deficit. Screening and vaccination protocols may prevent the spread of the hepatitis B infection, healthcare losses and financial loss.

Pathological, biochemical and haematological investigations on the protective effect of alpha-lipoic acid in experimental aflatoxin toxicosis in chicks.

1. The purpose of this study was to investigate the protective effect of alpha-lipoic acid (LA) on aflatoxin (AF) toxicosis in chicks. 2. Groups of 10 Ross PM3 chicks were given, for 21 d, no AF (C), 60 mg/kg/bwt of alpha-lipoic acid (LA), 150 ppb of aflatoxin (AF1), 150 ppb of aflatoxin plus 60 mg/kg/bwt of alpha-lipoic acid (AF1 + LA), 300 ppb of aflatoxin (AF2), and 300 ppb of aflatoxin plus 60 mg/kg/bwt of alpha-lipoic acid (AF2 + LA). Before the animals were killed, blood samples were drawn for haematological analysis, and then tissue samples were collected for histopathological investigation. Immunohistochemical staining was performed against inducible nitric oxide synthase (iNOS) and nitrotyrosine on liver samples. Apoptotic cell death in liver was assessed by in situ TUNEL assay. The malondialdehyde (MDA) and reduced glutathione (GSH) concentrations in liver and kidney were also determined. 3. Hydropic degeneration and occasional necrosis, bile duct hyperplasia and periportal fibrosis were observed in the livers of AF-treated groups. The severity of these changes was reduced in LA-supplemented AF groups. Occasionally, thymic cortical atrophy, lymphoid depletion in spleen and bursa of Fabricius, and degeneration in the kidney tubule epitheliums were detected in AF groups. The severity of these degenerative changes was slightly reduced in LA supplemented groups. 4. There was moderate to strong iNOS and nitrotyrosine immunoreactivity in the livers of AF groups, while decreased immunoreactivity was observed against both antibodies in the LA supplemented groups. Apoptotic cells were numerous in the AF groups, while greatly reduced in LA supplemented groups. 5. In the liver and kidney of AF-treated groups given 300 ppb of aflatoxin, MDA concentrations were increased as GSH decreased, compared to the control group. LA supplementation of AF-treated birds improved the results compared to the AF only groups, however a statistical difference was observed only in liver tissues between AF2 + LA and AF2 groups. Haematological variables showed no differences among the groups. 6. In conclusion, supplementation of feed with the antioxidant LA, might ameliorate the degenerative effects caused by aflatoxin due to lipid peroxidation.

A short course of add-on adefovir dipivoxil treatment in lamivudine-resistant chronic hepatitis B patients.

The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/40, mean age: 42.9+/-13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.

On demand pancreatic stenting in chronic pancreatitis might provide good palliation of pain.

BACKGROUND AND AIM: Chronic pancreatitis (CP)-related pain is a considerable problem in gastroenterology practice that frequently requires several endoscopic interventions. We aimed to investigate the efficacy of pancreatic duct stenting performed on demand, instead of at defined intervals, for the management of the CP-related pain. METHODS: This study is a retrospective evaluation of thirteen years of data. Sixty-seven patients with CP who suffered from intractable pain were enrolled in the study. Pancreatic stenting was performed mainly with single stents according to the diameter of the pancreatic duct and width of the stricture or, less frequently, with multiple stents aiming to achieve stricture resolution. The subsequent endoscopic session was scheduled based on the patient's symptoms. RESULTS: Overall, 65 of 67 patients underwent successful pancreatic cannulation (technical success rate 97%). Fifty-seven patients with a pancreatic stenting history were still undergoing follow-up. Of these patients, 26 patients still had pancreatic ductal stents; however, the stents were removed from 31 patients. Only 8 patients (25%) required further endoscopic or surgical intervention because of the re-emergence of pain after a median stent-free period of 17 months (3-127 months). One patient with a biliary stricture and one patient with a pancreatic mass underwent surgery. Pancreatic stents remained for a median length of 14 months (3-84 months). During the follow-up period, 55 of 65 patients became pain-free or had partial pain relief (clinical success rate 84%). CONCLUSIONS: On demand replacement of pancreatic stent is feasible in patients with CP and it might provide a good palliation of CP-related pain.

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon.

Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment-naïve, 14 had previously used IFN), efficacy of 1-year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment-naïve patients. In both treatment-naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN-LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN +/- LAM than with LAM alone (P < 0.05). In treatment-naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Spontaneous abdominal esophageal perforation in a patient with mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder caused by thymidine phosphorylase deficiency. Severe denutrition is almost constant during the course of the disease which leads to severe malnutrition and requires long-term parenteral nutrition in most cases. Patients with MNGIE syndrome and chronic intestinal pseudo-obstruction have a particularly poor prognosis and they usually die around 40 years of age. Gastrointestinal perforation associated with MNGIE is extremely rare. Herein we present our unique case with MNGIE associated abdominal esophageal perforation.

Effect of clinoptilolite on serum biochemical and haematological characters of broiler chickens during aflatoxicosis.

Clinoptilolite (CLI, a natural zeolite) incorporated into the diet at 1.5 and 2.5 per cent were evaluated for their ability to reduce the deleterious effects of 2.5 mg total aflatoxin (AF) kg(-1)diet on broiler chickens from 1 to 21 days of age. In total 360 broiler chicks were divided into six equal treatment groups (control, AF, CLI (1.5 per cent), AF plus CLI (1.5 per cent), CLI (2.5 per cent) and AF plus CLI (2.5 per cent)). When compared with the controls, AF treatment significantly decreased serum total protein, albumin, inorganic phosphorus, uric acid, total cholesterol and the values of haematocrit, red blood cell counts, mean corpuscular volume, haemoglobin, thrombocyte counts, percentage of monocyte counts; increased values of white blood cell and heterophil counts. The addition of CLI (1.5 per cent) and CLI (2.5 per cent) to the AF -containing diet reduced the adverse effects of AF and should be helpful in a solution to the aflatoxicosis problem in poultry.

Anticardiolipin antibodies and retinal vascular complications in Behçet's disease.

BACKGROUND AND OBJECTIVE: Intravascular thrombosis is a well-recognized feature of Behçet's disease (BD). In this study, the existence of a connection between serum anticardiolipin (aCL) antibodies and retinal vascular complications in BD is investigated. PATIENTS AND METHODS: Serum aCL antibody levels were quantified in 31 patients with BD, all of whom fulfilled the major criteria of the disease. Patients were evaluated in terms of retinal vascular complications. Serum aCL antibody levels were determined through the ELISA method. Statistical analysis was performed with the chi-squared test and the Fisher exact test. RESULTS: Of 12 patients with high aCL antibody levels, retinal vascular thrombosis was detected in 5 and retinal vasculitis was present in 8. However, there was no statistically significant relation between these complications and serum aCL antibody elevation (P > .05). CONCLUSION: Based on this series of 31 patients with BD, there does not seem to be a significant correlation between retinal vascular complications and serum aCL antibody levels.

Evaluation of preoperative predictors of development of pouchitis after ileal-pouch-anastomosis in ulcerative colitis.

INTRODUCTION: In this retrospective study, we aimed to evaluate preoperative predictive risk factors for development of pouchitis in the ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA). METHODS: The records of UC patients who underwent IPAA surgery and were under follow-up in the inflammatory bowel disease (IBD) clinic of our hospital between January 1994 and September 2009 were retrieved. Preoperative clinical, biochemical, and endoscopic findings, as well as preoperative endoscopic activity index (EAI), preoperative disease activity index (DAI) and operative characteristics were recorded. Patients with endoscopic, histological and clinical findings consistent with pouchitis were identified. RESULTS: Out of a total of 49 patients who underwent IPAA for UC, pouchitis was identified in 20 (40.8%) of them. Overall, 37 (75.5%) patients had chronic active disease, eight (16.3%) patients had chronic intermittent disease with frequent relapses, and four (8.2%) patients had fulminant colitis prior to surgery. There was a statistically significant difference (P=0.02) among these patients for the development of pouchitis in postoperative period. The mean EAI (10.1 vs. 8.7, P=0.02) and DAI (10.0 vs. 8.6, P<0.01) in patients with pouchitis were significantly higher than that of patients who did not develop pouchitis. Multivariate analysis revealed steroid dependency (P=0.02), and a higher DAI (P=0.02) to be independent risk factors for the development of pouchitis. CONCLUSION: A more severe preoperative clinical course and steroid dependency, as well as higher endoscopic and disease activity scores may be useful as preoperative predictors of subsequent pouchitis in UC patients undergoing IPAA surgery.

Concomitant Hodgkin's lymphoma and gastric adenocarcinoma: a rare coincidence.

Gastric adenocarcinomas may be seen together with colon, prostate, breast, liver, lung and gynecological malignancies as synchronous or metachronous cancer. However, Hodgkin's lymphoma (HL) is rarely diagnosed with solid tumors. Herein, a 72-year-old man with both gastric adenocarcinoma and HL has been presented. Mass lesions far away from the primary tumor in cancer patients can be not only the sign of distant metastasis but also another primary malignancy. In the English literature, synchronous gastric adenocarcinoma and HL has been rarely reported, and as far as we know, this is the third case to be reported.

A pilot study of 2 years of interferon treatment in patients with chronic delta hepatitis.

High dose interferon treatment for 1 year is the only established treatment for chronic hepatitis D, but it is associated with a high relapse rate after treatment discontinuation. In this study, patients were treated with 10 MU interferon alpha 2b, thrice weekly for 2 years. Twenty-three patients were recruited and 15 completed the 2-year treatment and 6 months follow-up periods. Treatment response was assessed biochemically [normal alanine aminotransferase (ALT)], virologically (undetectable hepatitis D virus RNA) and histologically (at least 2 point decrease in the Knodell score) at the end of treatment (EOT) and at the end of follow-up. Out of 15 patients who finished the 2-year treatment period, seven patients (47%) had a biochemical response but only two (13%) had a normal ALT after follow-up. ALT decreased from the baseline value of 143.1 +/- 121.7 (mean +/- SD) to 39.7 +/- 20.6 (P < 0.01) at EOT. Virological response was observed in six patients at EOT and in two patients at follow-up. Two patients lost hepatitis B surface antigen. Of the 12 patients with paired liver biopsies, a histological improvement was observed in eight patients. Interferon treatment leads to a complete or partial response in a substantial number of patients but 2 years of treatment does not appear to increase sustained response rates over 1 year treatment.

Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat.

Fatigue associated with cholestasis may impair health-related quality of life. The pathogenesis of this symptom is largely unknown, but it has been suggested that central serotoninergic neurotransmission may be implicated and that serotonin 1A receptor agonists may yield improvement. The aim of this study was to study the central serotoninergic system, specifically the serotonin (5-HT)(1A) receptor-mediated pathway of serotoninergic neurotransmission, in a bile duct resection rat model of cholestasis. Fatigue was assessed in the forced swim test in sham and bile duct-resected rats. The serotonin behavioral syndrome, which includes hyperlocomotion, was assessed in both groups of rats after escalating doses of the 5-HT(1A) receptor agonist 8-hydroxy(di-n-propylamine)tetralin (8-OH DPAT). 5-HT(1A) and 5-HT(2) receptor densities were explored in four brain regions using a receptor-binding assay. Extracellular 5-HT and 5-hydroxyindoleacetic acid were measured via in vivo brain dialysis. Bile duct-resected rats spent more time floating in the forced swim test, and 8-OH DPAT decreased floating time in cholestatic rats (P < .01). Dose-response curves created with 8-OH DPAT for the serotonin behavioral syndrome were similar in bile duct-resected and sham-operated rats. 5-HT(1A) and 5-HT(2) receptor densities in most brain regions and extracellular serotonin levels were similar in both groups of rats. In conclusion, 5-HT(1A) receptor agonist-induced amelioration of fatigue in cholestatic rats may be nonspecific and not linked to reversal of the pathophysiology of fatigue associated with cholestasis; however, these data do not exclude a potential role of the central serotoninergic system in the evolution of fatigue.

Correlation of clinical and neuroradiological findings in down-gaze palsy.

BACKGROUND: Isolated down-gaze palsy is the least common pathology of vertical gaze. Patients with low-gaze palsy may consult an ophthalmologist with difficulty in reading and this may be the only ocular finding of a central nervous system lesion. METHODS: A 43-year-old man with isolated down-gaze palsy was examined. The medical history of the patient revealed that he had had myocardial infarction. RESULT: Magnetic resonance imaging disclosed an ischemic area at the right thalamus. CONCLUSION: Down-gaze palsy may be an important sign for the diagnosis of thalamic infarctions due to embolic syndrome.