On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients.

BACKGROUND & AIMS: We assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. METHODS: Ninety-five HBeAg-negative patients received peginterferonalfa-2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA <2000 IU/ml at study week 96. RESULTS: Twenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline ≥10% from baseline to week 24 was significantly associated with SR [81% (17/21) vs 37% (21/57); Odds ratio: 7.286 (2.162-24.552), P = 0.001]. The PARC rule (no decrease in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of ≥10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1 achieved SR; negative predictive value: 93%). CONCLUSIONS: In HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline >10% at 24 weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074.

Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.

BACKGROUND: Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. METHODS: After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system). FINDINGS: Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug. INTERPRETATION: In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis. FUNDING: Gilead Sciences.

Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study.

BACKGROUND & AIMS: Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years. METHODS: Prospective data were extracted from the HepNet.Greece Cohort-Study. RESULTS: Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p<0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p<0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)]. CONCLUSIONS: In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute >50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.

Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg(+) or HBeAg(-)). METHODS: After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg). RESULTS: At week 144, 87% of HBeAg(-) and 72% of HBeAg(+) patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg(-) and 71% of the HBeAg(+) patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg(+) patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years. CONCLUSIONS: TDF was safe and effective in the long-term management of HBeAg(+) and HBeAg(-) patients with chronic hepatitis B.

Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.

BACKGROUND: Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase. METHODS: In two double-blind, phase 3 studies, we randomly assigned patients with hepatitis B e antigen (HBeAg)-negative or HBeAg-positive chronic HBV infection to receive tenofovir DF or adefovir dipivoxil (ratio, 2:1) once daily for 48 weeks. The primary efficacy end point was a plasma HBV DNA level of less than 400 copies per milliliter (69 IU per milliliter) and histologic improvement (i.e., a reduction in the Knodell necroinflammation score of 2 or more points without worsening fibrosis) at week 48. Secondary end points included viral suppression (i.e., an HBV DNA level of <400 copies per milliliter), histologic improvement, serologic response, normalization of alanine aminotransferase levels, and development of resistance mutations. RESULTS: At week 48, in both studies, a significantly higher proportion of patients receiving tenofovir DF than of those receiving adefovir dipivoxil had reached the primary end point (P<0.001). Viral suppression occurred in more HBeAg-negative patients receiving tenofovir DF than patients receiving adefovir dipivoxil (93% vs. 63%, P<0.001) and in more HBeAg-positive patients receiving tenofovir DF than patients receiving adefovir dipivoxil (76% vs. 13%, P<0.001). Significantly more HBeAg-positive patients treated with tenofovir DF than those treated with adefovir dipivoxil had normalized alanine aminotransferase levels (68% vs. 54%, P=0.03) and loss of hepatitis B surface antigen (3% vs. 0%, P=0.02). At week 48, amino acid substitutions within HBV DNA polymerase associated with phenotypic resistance to tenofovir DF or other drugs to treat HBV infection had not developed in any of the patients. Tenofovir DF produced a similar HBV DNA response in patients who had previously received lamivudine and in those who had not. The safety profile was similar for the two treatments in both studies. CONCLUSIONS: Among patients with chronic HBV infection, tenofovir DF at a daily dose of 300 mg had superior antiviral efficacy with a similar safety profile as compared with adefovir dipivoxil at a daily dose of 10 mg through week 48. (ClinicalTrials.gov numbers, NCT00116805 and NCT00117676.)

Target organ damage in "white coat hypertension" and "masked hypertension".

BACKGROUND: In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. METHODS: A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. RESULTS: WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 +/- 30.6, 107.1 +/- 29.1 vs. 101.4 +/- 29.9 g/m(2) and 0.68 +/- 0.16, 0.68 +/- 0.21 vs. 0.63 +/- 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 +/- 25.9 vs. 101.4 +/- 29.9 g/m(2)); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 +/- 0.15 vs. 0.63 +/- 0.15 mm). CONCLUSIONS: WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

A comparative study of 10-Fr vs. 7-Fr straight plastic stents in the treatment of postcholecystectomy bile leak.

BACKGROUND: Biliary decompression is a key factor in the treatment of postcholecystectomy bile leak. However, the optimal size of the stent introduced by therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is yet to be determined. The aim of the study was to compare the effectiveness of two straight plastic stents with different sizes (10-Fr and 7-Fr) in the treatment of postcholecystectomy bile leak. METHODS: Between January 2003 and August 2006, 63 patients underwent therapeutic ERCP for postcholecystectomy bile leak. After visualization of the bile duct injury, endoscopic sphincterotomy was performed and the patients were randomized to receive either a 7-Fr (31 subjects, group A) or a 10-Fr (32 subjects, group B) straight plastic stent for four weeks. The success of the endoscopic treatment was determined by the elimination of the symptoms and the removal of the drain without any adverse outcomes. RESULTS: The endoscopic intervention was successful in 29 patients of group A (93.54%) and in 31 patients of group B (96.87%). In the remaining two patients of group A, the 7-Fr stent was substituted by a 10-Fr stent after 7 days because the leak remained unaffected, resulting in healing of the leaks. Surgery was required in the remaining one patient of group B. Eight patients developed post-ERCP pancreatitis (5 mild, 2 moderate, 1 severe), which was treated conservatively. CONCLUSIONS: This trial suggests that the stent size does not affect the outcome of the endoscopic intervention in postcholecystectomy bile leaks due to minor biliary tract injury; however, larger cohorts are required to confirm the optimal stent size in bile leaks due to major bile duct injury.

Accidental ingestion of an air-water syringe tip during routine dental treatment: a case report.

Accidental ingestion of instruments or their components is a possible complication of dental treatment. Although in many cases the foreign object can pass through the gastrointestinal tract without any need for surgical intervention to retrieve it, sometimes such incidents can be life-threatening. This paper reports a case of accidental ingestion of an air-water syringe tip during routine dental treatment for which endoscopic retrieval was required. The present case highlights the need for dental professionals to be aware of the fact that dental equipment comprising multiple components may be associated with a risk of accidental detachment of a component and its ingestion or aspiration by a patient receiving treatment.

Postprandial response of bone turnover markers in patients with Crohn's disease.

AIM: To investigate the postprandial response of bone turnover markers in patients with Crohn's disease (CD). METHODS: Fifty nine patients with CD aged 38 ± 14 years, and 45 healthy individuals matched for age and body mass index were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) and the bone formation marker procollagen type I N propeptide were measured. Activity of the disease was assessed by calculation of the Crohn's disease activity index (CDAI). RESULTS: Serum CTX-I was significantly higher in patients compared to controls (CTX-I: 453 ± 21 pg/mL vs 365 ± 25 pg/mL, P = 0.008), and values were significantly correlated with the activity of the disease (r = 0.435, P = 0.001). Results from OGTT-induced suppression of CTX-I showed two different trends. Patients with more active disease (assessed as CDAI > 150) had a more excessive suppression of CTX-I compared to controls (55% vs 43% P < 0.001), while patients on remission (assessed as CDAI < 150) demonstrated an attenuated CTX-I suppression (30% vs 43% P < 0.001). In line with this, CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease (r = 0.913, P < 0.001). CONCLUSION: The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.

Predictive factors for post-ERCP pancreatitis: a large-scale single expertized endoscopist study.

BACKGROUND: Pancreatitis remains the most common and feared complication of therapeutic endoscopic cholangiopancreatography (ERCP) associated with substantial morbidity. The patient-related and procedure-related independent risk factors for post-ERCP pancreatitis (PEP) in a large case volume by a single experienced endoscopist have been investigated only by few studies. The aim of the study was to investigate patient-related and procedure-related risk factors for PEP collected by a defined protocol on patients who underwent therapeutic ERCP in a single endoscopic unit during the last 8 years. PATIENTS AND METHODS: Our retrospective cohort study included a total of 2688 therapeutic ERCPs enrolled in the final analysis. The impact of the risk factors on PEP development was investigated by univariate and multivariate analysis. PEP was diagnosed and its severity was graded according to the consensus criteria. RESULTS: With the exception of history of pancreatitis, there was no other statistically significant difference of patients' characteristics between patients with and without PEP. Female sex, age, difficult cannulation, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct, and suprapapillary fistulotomy were not found to be risk factors for PEP by univariate and multivariate analysis. Both univariate and multivariate analysis showed history of acute pancreatitis, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first-class and second-class pancreatic ductules, and acinarization as independent risk factors for PEP. CONCLUSIONS: History of acute pancreatitis, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first-class and second-class pancreatic ductules, and acinarization were all identified as independent risk factors for PEP.

Sequential or simultaneous placement of self-expandable metallic stents for palliation of malignant biliary and duodenal obstruction due to unresectable pancreatic head carcinoma.

BACKGROUND: Pancreatic cancer is generally not amenable to curative resection, and self-expanding metallic stents have been used to relieve obstruction of bile duct and duodenum in patients with unresectable pancreatic cancer. However, both relative experience with sequential or simultaneous endoscopic stents placement in biliary and duodenal stricture and long-term efficacy of these stents are limited. The aim of this study was to present our experience on the effectiveness of this form of endoscopic treatment. PATIENTS AND METHODS: We performed a retrospective review of all patients undergoing sequential or simultaneous biliary and duodenal stent placement for biliary and symptomatic duodenal obstruction due to unresectable pancreatic head carcinomas in 4 tertiary endoscopic centers. Data were collected from endoscopy and outpatient clinic reports, x-rays, and telephone calls. All patients were followed until their death. Endpoints included technical and clinical success, stent long-term patency, and survival. RESULTS: Thirty-nine patients with unresectable pancreatic head cancer were included. Biliary or duodenal stenting was unsuccessful in 7 patients (17.9%). The remaining 32 patients (median age: 77 y; range: 52 to 82 y), with locally advanced (n=21) or metastatic disease (n=11), were studied. Twenty-one patients (65.6%) received at least first-line chemotherapy. Overall median survival was 9 months (range: 2 to 22 mo), being higher in locally advanced (median survival: 11.5 mo, range: 4 to 22 mo) than metastatic disease (median survival: 3 mo, range: 2 to 5.5 mo) (P<0.001). Median duodenal and biliary patency was 3 months (range: 1 to 12 mo) and 9 months (range: 2 to 22 mo), respectively (P<0.05). Nine of 32 patients (28.1%) required reintervention for recurrent symptoms. No major complications or death occurred in relation to endoscopic treatment. CONCLUSIONS: Placement of self-expandable metal stents is a safe and efficacious palliation method for biliary and duodenal obstruction due to unresectable pancreatic head carcinoma. The majority of patients do not require reintervention and those who require can usually be managed nonoperatively.

Endoclipping treatment of life-threatening rectal bleeding after prostate biopsy.

Rectal bleeding is frequently seen in patients undergoing transrectal ultrasound (TRUS)-guided multiple biopsy of the prostate, but is usually mild and stops spontaneously. We report what is believed to be the first case of life-threatening rectal bleeding following this procedure, which was successfully treated by endoscopic intervention through placement of three clips on the sites of bleeding. This case emphasizes endoscopic intervention associated with endoclipping as a safe and effective method to achieve hemostasis in massive rectal bleeding after prostate biopsy. Additionally, current data on the complications of the TRUS-guided multiple biopsy of the prostate and the options for treating fulminant rectal bleeding, a consequence of this procedure, are described.

Severe dysphagia due to a huge epiphrenic diverticulum: long-term treatment with balloon dilation and botulinum toxin injection: a case report.

We herein describe the first case of a high elderly patient with severe dysphagia in solids and liquids, caused by a huge epiphrenic diverticulum, who was treated with combined therapy of balloon dilation and botulinum toxin injection. Due to comorbid associated diseases the patient was unsuitable to withstand surgical or laparoscopic intervention. Treatment with botulinum toxin injection at the region of lower esophageal sphincter was unsuccessful. Combined therapy with balloon dilatation and botulinum toxin injection at the compressed part of esophageal lumen by the diverticulum resulted in improvement in dysphagia and malnutrition. During the long-term follow-up the patient developed symptomatic relapses, successfully treated by subsequent combined therapy resulting in longer-lasting symptom relief.