Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension.

BACKGROUND/AIMS: Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS: We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS: At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION: In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

Ultrasound-guided liver biopsy in real life: comparison of same-day prebiopsy versus real-time ultrasound approach.

BACKGROUND AND AIM: Currently, an increasing number of liver biopsies are performed by radiologists under real-time ultrasound control. A routine ultrasound assessment of a puncture site before performing percutaneous biopsy is reported to increase diagnostic yield and decrease complication rates. It is not clear if real-time ultrasound is superior to marking the puncture site before biopsy as regards reducing biopsy size and avoiding fragmentation and complications. The aim of this study was to compare ultrasound assessment of the puncture site before performing percutaneous liver biopsy with real-time ultrasound liver biopsy for suspected diffuse liver disease. METHODS: Consecutive percutaneous liver biopsies (n = 631) for diffuse liver disease were evaluated. Group A consisted of patients who had real-time guided-ultrasound biopsy performed by radiologists (241 patients; M/F, 35/106; median age 48 year [range, 17-76]; needle 18 G). Group B patients were assessed by radiologists using ultrasound of the puncture site on the same day that biopsies were performed by experienced gastroenterologists/hepatologists on the ward using the marked site (390 patients; M/F, 276/114; median age 43 year [range, 15-75]; needle 16 G). RESULTS: There were no differences in severity of liver disease, establishing a diagnosis (OR, 1.92 [95% CI, 0.84-4.34]; P = 0.12), length of liver biopsy specimens, number of fragments or complications. Two independent variables were significantly associated with a histological diagnosis: longer biopsy length (P < 0001) and fragment number of two or less (P < 0.001). CONCLUSION: Real-time ultrasound did not improve diagnostic yield or result in fewer complications. Marking the puncture site seems adequate and has the practical advantage that it takes up less of the radiologists' time.

A single alcohol ingestion does not affect serum hepatitis C virus RNA in patients with chronic hepatitis C.

BACKGROUND AND AIM: The safe level of alcohol ingestion in sporadic drinkers with hepatitis C is unknown. Our aim was to evaluate the effect of a single moderate alcohol intake on serum HCV RNA concentrations and hepatic function in patients with chronic HCV infection. METHODS: Twenty-one patients with chronic hepatitis C were randomly assigned to consume 50 g alcohol (group 1) or a non-alcoholic beverage (group 2). In both groups, serum ethanol, serum HCV RNA, transaminase and gamma-glutamyltranspeptidase (gamma-GT) levels were measured just before alcohol intake and after 1, 2, 8, 24 h and 1 week's time. RESULTS: The maximum concentration of ethanol in the blood was observed at the first hour after alcohol intake. No significant changes were observed in serum HCV RNA after alcohol intake. Repeated measurements of HCV RNA among the two groups revealed no difference (P = 0.215). Similarly, no difference was observed in transaminase and gamma-GT levels at different time points in each group or among the groups [(ALT (P = 0.082), AST (P = 0.33), gamma-GT (P = 0.538)]. CONCLUSIONS: In patients with chronic hepatitis C, a single intake of 50 g alcohol does not affect liver biochemistry and HCV RNA concentrations. Therefore, it is a matter of further research whether sporadic drinking of light or moderate amounts of alcohol should be avoided in patients with chronic hepatitis C.

Interferon-alpha plus lamivudine vs lamivudine reduces breakthroughs, but does not affect sustained response in HBeAg negative chronic hepatitis B.

AIM: The HBeAg negative form of chronic hepatitis B (CHB) predominates in the Mediterranean area and has a rising frequency in Europe and North America. At present there are three approved therapies for patients with CHB: interferon-alpha (IFN-alpha), lamivudine and adefovir dipivoxil. Unfortunately, none of these drugs are effective in achieving a sustained response in patients with HBeAg negative CHB. Therefore, new therapeutic approaches have been examined. Our aim was to investigate the efficacy of combination treatment of IFN-alpha and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAg-negative hepatitis B patients. METHODS: Fifty consecutive patients were randomly assigned to receive IFN-alpha-2b (5 MU thrice per week, n = 24) plus lamivudine (100 mg daily) or lamivudine only (n = 26) for 24 mo. Patients were followed up for further 6 mo. The primary outcome was the proportion with sustained virological response (undetectable serum HBV DNA concentrations) and or sustained biochemical response (transaminase levels within normal range) at 30 mo (6 mo after the end of therapy). Secondary end-points were timed from initial virological (biochemical) response to VBR (BBR, respectively) and the emergence of YMDD mutants across the two arms. RESULTS: Five of twenty-four (21%) patients in the combination arm vs 3/26 (12%) in the lamivudine arm had sustained response (i.e., normal serum transaminase levels and undetectable HBV DNA by PCR assay) 6 mo after treatment discontinuation. A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receiving combination treatment (10% vs 46%, P = 0.01 and 14% vs 46%, P = 0.03, respectively). Time from initial virologic response to virologic breakthrough (VBR) was greater among initial responders receiving combination treatment compared to those receiving lamivudine (22.9 mo vs 15.9 mo, respectively; P = 0.005). CONCLUSION: Our results demonstrate that IFN-alpha plus lamivudine combination therapy did not increase the sustained response, compared to lamivudine. However, combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development.

Impact of capsule endoscopy in obscure small-bowel bleeding: defining strict diagnostic criteria for a favorable outcome.

BACKGROUND: The most frequent indication for capsule endoscopy is to diagnose the cause of obscure GI bleeding. The objective of the study was to determine the impact of capsule endoscopy on the outcome of patients with GI bleeding of obscure origin. METHODS: Ninety-six patients (53 men, 43 women; mean [standard deviation] age, 60.84 years [16.55 years]) were enrolled in the study. All patients have been subjected to gastroscopy, colonoscopy, small-bowel barium follow-through or enteroclysis, and push enteroscopy; no bleeding site had been identified. Capsule endoscopy was performed with the Given M2A video capsule system. By using strict criteria, studies were classified as having positive findings, findings of uncertain significance, and no findings. Outcome was defined as continued or complete resolution of bleeding. RESULTS: Positive findings, findings of uncertain significance, and no findings were identified in 41.7%, 20.8%, and 37.5% of our study population, respectively. The most common lesions seen were angiodysplasias of the small intestine. Therapeutic intervention was possible in 82.5% of patients with positive findings and in 35.0% of patients with findings of uncertain significance. Complete resolution of bleeding, after a median (interquartile range) follow-up period of 14 months (9-17 months), occurred significantly more often in patients with positive findings (68.4%) compared with patients with findings of uncertain significance and no findings (40.8%, p = 0.009). CONCLUSIONS: Capsule endoscopy increases the diagnostic yield in the workup of patients with obscure small-bowel bleeding. Strictly defined positive findings are associated with a favorable outcome.

Long-term acid suppressive therapy may prevent the relapse of lower esophageal (Schatzki's) rings: a prospective, randomized, placebo-controlled study.

OBJECTIVES: Distal esophageal (Schatzki's) rings are a frequent cause of dysphagia. Bougienage is generally effective, but relapses are common. The aim of this study was to evaluate the effect of long-term antisecretory therapy on the relapse rate of lower esophageal rings after successful bougienage with Savary dilators. PATIENTS AND METHODS: The study was performed on 44 consecutive patients with symptomatic Schatzki's rings, detected endoscopically, and/or radiologically. Graded esophageal dilation was performed as an outpatient procedure in a single session. After appropriate assessment with esophageal manometry and 24-h ambulatory esophageal pH monitoring, patients with documented GERD (n = 14) were treated with long-term omeprazole therapy. The remaining patients were blindly randomized to receive maintenance treatment with either omeprazole (group A-15 patients) or placebo (group B-15 patients). The necessity for redilation after documentation of the ring with endoscopy and/or radiology was considered as a relapse of the ring. The relapse rate was evaluated in all groups. RESULTS: All bougienages were performed without significant side effects. Eight patients (8 of 44, 18.2%) had one or more relapses after a mean (SD) of 19.0 (10.1) months. Patients with (n = 14) or without (n = 30) GERD were comparable with respect to sex, age, body mass index, cigarette and alcohol consumption, diameter of the esophageal lumen at the level of the ring, resting lower esophageal sphincter pressure, duration of dysphagia, need for taking antacids during the follow-up period, and duration of follow-up. There were no recurrences of Schatzki's ring in the group of patients with documented GERD (follow-up [mean +/- SD]: 43.8 +/- 9.3 months, range: 27-62). In group A (follow-up [mean +/- SD]: 37.1 +/- 17.1 months, range: 11-66), one patient relapsed after 13 months, while in group B (follow-up [mean +/- SD]: 34.3 +/- 14.6 months, range: 10-58), seven patients relapsed after a mean (SD) of 19.9 (10.6) months. The actuarial probability of relapse was higher in patients without therapy (group B) (p= 0.008). CONCLUSIONS: Our data support the hypothesis that, in patients with symptomatic Schatzki's rings, acid suppressive maintenance therapy after bougienage may prevent relapse of the ring.

Somatostatin inhibits gastric acid secretion more effectively than pantoprazole in patients with peptic ulcer bleeding: a prospective, randomized, placebo-controlled trial.

OBJECTIVE: Gastric acid inhibition is beneficial in the management of peptic ulcer bleeding (PUB). The aim of this double-blind study was to test whether somatostatin (SST) increases intragastric pH in PUB as compared with pantoprazole (PAN) and placebo (PLA). MATERIAL AND METHODS: Eligible patients were randomized to receive SST (500 microg/h+250 microg bolus), or PAN (8 mg/h+80 mg bolus) or PLA (normal saline) i.v., for 24 h. All patients underwent gastric pH monitoring during the infusion of the trial drugs. RESULTS: The three groups (SST, n=14; PAN, n=14; PLA, n=15) were comparable for age, gender, aetiology of PUB and laboratory data at admission. Mean (+/-SE) baseline pH levels in the fundus increased during the administration of the trial drugs (SST: 1.94+/-0.18 to 6.13+/-0.37, p<0.0001; PAN: 1.93+/-0.16 to 5.65+/-0.37, p<0.0001; PLA: 1.86+/-0.12 to 2.10+/-0.15, p=0.0917). During the first 12 h of infusion, the mean (+/-SE) percentage time spent above pH 4.0 and 5.4 was higher with SST versus PAN (84.4%+/-4.8 versus 55.1%+/-8.3, p=0.0049 and 74.2%+/-6.5 versus 47.1%+/-8.3, p=0.0163, respectively) and there was a trend favouring the SST group regarding the time spent above pH 6.0 and 6.8 (65.7%+/-6.4 versus 43.3%+/-8.2, p=0.0669 and 49.2%+/-7.7 versus 28.4+/-6.6, p=0.0738, respectively). CONCLUSIONS: In PUB, both SST and PAN inhibit gastric acid secretion as compared with placebo. However, during the first 12 h of the infusion, SST was more effective than PAN in maintaining high intragastric pH. These results may provide a rationale for the administration of SST in PUB.

Bowel preparation increases the diagnostic yield of capsule endoscopy: a prospective, randomized, controlled study.

BACKGROUND: The aim of this study was to determine the value of small-bowel preparation for patients undergoing capsule endoscopy. METHODS: The study design was prospective, randomized, and controlled. Eighty patients referred for capsule endoscopy were randomized into two equal groups. Patients in Group A (mean age 54.40 [15.65] years) ingested 2 L of a polyethylene glycol/electrolyte solution 16 hours before the test, whereas patients in Group B (mean age 59.85 [14.58] years) prepared for the procedure by taking only clear liquids during the prior day. The primary outcome evaluated was the effect of bowel preparation on the quality of capsule images, as assessed with an objective scoring system in which cleansing was graded as "adequate" or "inadequate" by blinded examiners. A secondary outcome was the effect of bowel preparation on diagnostic yield. For this purpose, the results of capsule endoscopy were classified as positive findings, findings of uncertain significance, and no findings. RESULTS: Cleansing of the small intestine was considered "adequate" in 36 patients in Group A (90%) vs. 24 patients of Group B (60%) (p = 0.004). A diagnosis was established in 26 patients in Group A (65%) compared with 12 patients in Group B (30%) (p = 0.003). CONCLUSIONS: Bowel preparation before capsule endoscopy improves visualization of the small intestine, which may lead to an improvement in diagnostic yield.

Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis.

During variceal bleeding, several factors may increase portal pressure, which in turn may precipitate further bleeding. This study investigates the early effects of endoscopic injection sclerotherapy (EIS) and endoscopic band ligation (EBL) on hepatic venous pressure gradient (HVPG) during acute bleeding and the possible influence in outcome. In 50 cirrhotic patients with bleeding esophageal varices treated with EIS (n = 25) or EBL (n = 25), we performed repeated HVPG measurements before and immediately after endoscopic treatment (time 0) and every 24 hours for a 5-day period. Endotherapy was continued until the varices were too small for further treatment. Both groups were comparable with regard to age, gender, Child-Turcotte-Pugh grade, and HVPG. In the EBL and EIS groups, a significant (P <.0001) increase was observed in mean portal pressure (20.7 mm Hg +/- 4.4 SD and 21.5 mm Hg +/- 4.5 SD, respectively) immediately after treatment (time 0) as compared with pretreatment (18.1 +/- 4.5 and 18.1 +/- 4.0). However, HVPG in the EBL group returned to baseline values within 48 hours after treatment, while in the EIS group it remained high during the 120-hour study period (P <.0001). Bleeding stopped in all patients after endotherapy. During the 42-day follow-up period, the rebleeding rate over time was lower in the EBL group compared with the EIS group (P =.024). Patients with an initial HVPG greater than 16 mm Hg had, despite endoscopic treatment, a significantly higher likelihood of death (P =.024) and overall failure (P =.037) [correction]. In conclusion, during acute variceal bleeding EIS, but not EBL, causes a sustained increase in HVPG, which is followed by a higher rebleeding rate.

Clinical course of lamivudine monotherapy in patients with decompensated cirrhosis due to HBeAg negative chronic HBV infection.

OBJECTIVES: We have evaluated the efficacy of long-term lamivudine monotherapy in patients with decompensated HBeAg-negative/HBV-DNA positive cirrhosis. METHODS: We analyzed the clinical course and outcome of lamivudine treatment in 30 consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg-negative controls matched for age and gender. RESULTS: Significant clinical improvement, defined as a reduction of at least two points in Child-Pugh score was observed in 23 of the 30 treated patients (76.6%) versus none of the 30 patients in the control group (p < 0.0001) after a mean follow-up of 20.6 +/- 12.1(+/-SD) months. There were 10 deaths in the treated group versus 24 in the control group (p= 0.07). Liver-related deaths occurred in five of the eight patients soon after the development of biochemical breakthrough. Patients with clinical improvement had better survival than patients with no improvement (p= 0.04) or those who developed biochemical breakthrough due to YMDD mutants (p= 0.001). CONCLUSIONS: Lamivudine significantly improves liver function in HBeAg-negative decompensated cirrhosis. However, the development of the biochemical breakthrough due to YMDD mutants is associated with fatal outcome.

Early increase of lower oesophageal sphincter pressure after band ligation of oesophageal varices in cirrhotics: an intriguing phenomenon.

AIM: We conducted a prospective, randomized comparison of endoscopic variceal ligation, sclerotherapy and metoclopramide injection in order to evaluate their early effect on lower oesophageal sphincter pressure. METHODS: Twenty-six patients with established cirrhosis and an episode of variceal bleeding controlled by one session of endoscopic therapy were randomized to undergo an oesophageal manometry. The patients' lower oesophageal sphincter pressure was evaluated, prior to and immediately after a single session of ligation (n = 10), a single session of sclerotherapy (n = 8) or a bolus injection of 20 mg metoclopramide hydrochloride (n = 8). RESULTS: Ligation produced a higher early increase in lower oesophageal sphincter pressure (from 12.3 +/- 2.3 to 27.8 +/- 3.0 mmHg) as compared with sclerotherapy (from 13.6 +/- 2.5 to 22.4 +/- 4.5 mmHg) or metoclopramide injection (from 14.6 +/- 3.2 to 22.5 +/- 2.9 mmHg); (P = 0.0001). CONCLUSION: Our data indicate that ligation of oesophageal varices produces an early increase in lower oesophageal sphincter pressure in cirrhotic patients.

Effects of endoscopic variceal treatment on oesophageal function: a prospective, randomized study.

AIM: Endoscopic methods are currently the most widely used techniques for the treatment of bleeding oesophageal varices (BOV). However, a number of complications may limit their usefulness. We conducted a prospective, randomized comparison of variceal ligation versus sclerotherapy in cirrhotics after the control of variceal haemorrhage to study the relative short-term risks of these two procedures with respect to oesophageal motility and gastro-oesophageal reflux. METHODS: Seventy-three patients with established cirrhosis and an episode of variceal bleeding controlled by one session of endoscopic therapy were randomized to treatment with sclerotherapy or ligation until variceal eradication. In 60 of these patients, oesophageal manometry and 24-h intra-oesophageal pH monitoring were performed at inclusion and 1 month after variceal eradication. RESULTS: After variceal eradication with sclerotherapy, peristaltic wave amplitude decreased from 76.2 +/- 14.7 mmHg to 61.6 +/- 17.7 mmHg (P = 0.0001), simultaneous contractions increased from 0% to 37.9% (P = 0.0008), and the percentage of time with pH < 4 increased from 1.60 +/- 0.25 to 4.91 +/- 1.16% in channel 1 (P = 0.0002) and from 1.82 +/- 0.27 to 5.69 +/- 1.37% in channel 2 (P = 0.0006). In contrast, the above parameters were not disturbed with ligation. CONCLUSION: Our data define the advantages of ligation over sclerotherapy with respect to post-treatment oesophageal dysmotility and associated gastro-oesophageal reflux.

Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis: a multicenter randomized controlled trial.

BACKGROUND: Octreotide is a potent inhibitor of pancreatic secretion, and corticosteroids suppress humoral and cellular activity. Both agents may reduce the frequency of post-ERCP pancreatitis. The aim of this study was to determine the effectiveness of octreotide and hydrocortisone in preventing post-ERCP pancreatitis. METHODS: Three hundred fifty-four patients were entered in to a multicenter randomized controlled trial of 100 microg subcutaneous octreotide (Group 1) versus 100 mg intravenous hydrocortisone (Group 2) versus normal saline solution as placebo (Group 3). All medications were administered approximately 30 minutes before the procedure. Patients were assessed clinically and serum amylase was also measured before the procedure and 3, 12, and 24 hours after the procedure. RESULTS: Three hundred forty patients were included in the analysis. Pancreatitis was observed in 11 of 112 patients (9.8%) in Group 1, 8 of 113 (7.1%) patients in Group 2, and in 15 of 115 (13.0%) patients in Group 3 (p = 0.32). The mean length of hospitalization in days was similar in all 3 groups: mean (SD) for Groups 1, 2, and 3 were, respectively, 3.6 (1.6) versus 2.9 (0.6) versus 4.3 (1.8) (p = 0.13). Multivariate logistic regression analysis showed that number of pancreatic injections, suspicion of sphincter dysfunction, therapeutic procedure, and age were risk factors for pancreatitis. CONCLUSIONS: The results of this trial indicate that octreotide and hydrocortisone do not prevent ERCP-induced pancreatitis.