Alec Avgerinos

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 rebleeding (P = .05) and death (P = .024) and overall failure (P = .037). In conclusion, during acute variceal bleeding EIS, but not EBL, causes a sustained increase in HVPG, which is followed by a higher rebleeding rate. (HEPATOLOGY 2004;39:1623–1630.)

Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding: A prospective randomized study

BACKGROUND/AIMS Long-term endoscopic injection sclerotherapy of oesophageal varices prevents rebleeding in patients with cirrhosis surviving an acute variceal bleeding episode. However, this treatment is associated with a substantial complication rate. Endoscopic band ligation is a newly developed technique in an attempt to provide a safer alternative. The aim of this study was to compare the efficacy and safety of injection sclerotherapy versus variceal ligation in the management of patients with cirrhosis after variceal haemorrhage. METHODS Seventy-seven patients with cirrhosis who proved to have oesophageal variceal bleeding were studied. After initial control of haemorrhage by sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37 to ligation. Both procedures were performed under midazolam sedation at intervals of 7-14 days until all varices in the distal oesophagus were eradicated or were too small to receive further treatment. RESULTS The eradication of varices required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The proportion of patients remaining free from recurrent bleeding against time was significantly higher in the ligation group as compared to the sclerotherapy group (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The mortality rate was similar in both groups (20% and 21%, respectively). CONCLUSIONS Variceal ligation is better than sclerotherapy in the long-term management of patients with cirrhosis after variceal haemorrhage which was initially controlled with sclerotherapy.

A prospective randomized trial comparing somatostatin, balloon tamponade and the combination of both methods in the management of acute variceal haemorrhage

The aim of this study was to compare the efficacy of: (i) somatostatin infusion, (ii) balloon tamponade with the Sengstaken-Blakemore tube and (iii) the combination of both methods, in the management of acute variceal haemorrhage. Ninety-two consecutive patients with liver cirrhosis who proved to have active variceal bleeding on emergency endoscopy were studied. Thirty-one patients were randomly assigned to an intravenous infusion of 250 micrograms/h of somatostatin (Group I), 30 to the Sengstaken-Blakemore tube (Group II) and 31 to the combination of both methods (Group III). Somatostatin was administered for 24 h, while the gastric and esophageal balloons remained inflated for 48 and 24 h, respectively, then deflated. Patients were under observation for a further 24-h period after withdrawal of treatment. If bleeding recurred, the same treatment was repeated in each group. Following treatment the bleeding was controlled initially in 22 patients (71%) in Group I, in 24 (80%) in Group II and in 25 (80.6%) in Group III. In Group II a significantly (p less than 0.05) higher proportion of patients (14/24) rebled as compared to Groups I (5/22) and III (6/25). Bleeding was controlled following retreatment in four, ten and five patients of the three respective groups. There were marked differences, in the number of complications noticed with each form of therapy. Only three patients (9.7%) in Group I developed complications (p less than 0.05) as compared to ten (33%) in Group II and ten (32%) in Group III. Hospital mortality in all three treatment groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing endoscopic sclerotherapy. A randomized controlled trial

The purpose of this study was to investigate the possible value of continuous administration of propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing chronic endoscopic sclerotherapy. Among 239 patients admitted for acute variceal bleeding, 85 with cirrhosis were randomized to receive sclerotherapy either alone (40) or in combination with propranolol (45). Sclerotherapy was carried out with an intravariceal injection of 5% ethanolamine oleate through a fiberoptic endoscope. The procedure was performed every week, until the esophageal varices at the gastroesophageal junction were too small for any further injections. Varices were reinjected if they recurred. Propranolol was given orally twice a day until heart rate was reduced by 25% in the resting position. The mean follow-up period was 23.2 and 24.2 months for sclerotherapy and the sclerotherapy plus propranolol groups, respectively. During this period a significant (P = 0.001) reduction in the recurrence of esophageal varices was observed in patients treated with the combination of sclerotherapy plus propranolol compared with those treated with sclerotherapy alone. However, the time of rebleeding from any source or from esophageal varices did not differ significantly between the two groups. In the sclerotherapy group 21 patients rebled (35 bleeding episodes) compared with 14 (22 episodes) in the combination therapy group. Patients in the sclerotherapy group were more prone to bleed from gastric varices and congestive gastropathy than patients treated with the combination of sclerotherapy plus propranolol (P = 0.012). Twenty-five patients in the endoscopic sclerotherapy group developed complications attributed to sclerotherapy compared with 23 patients in the sclerotherapy plus propranolol group. Complications directly attributable to propranolol were observed in 11 patients. Three of these patients stopped taking the drug due to heart failure (1) and flapping tremor (2). Eight patients (17.8%) died in the latter group while the corresponding figure in the sclerotherapy group was nine (22.5%). It is concluded that the continuous administration of propranolol may reduce incidences of recurrent upper gastrointestinal hemorrhage from gastric sources in patients with cirrhosis undergoing chronic sclerotherapy.

Long-Term Acid Suppressive Therapy May Prevent the Relapse of Lower Esophageal (Schatzki's) Rings: A Prospective, Randomized, Placebo-Controlled Study

OBJECTIVES:Distal esophageal (Schatzkis) 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 Schatzkis 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 Schatzkis 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 Schatzkis rings, acid suppressive maintenance therapy after bougienage may prevent relapse of the ring.

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.

Is banding ligation for primary prevention of variceal bleeding as effective as beta-blockers, and is it safe?

1. Hass M, Hannoun C, Kalinina T, Sommer G, Manegold C, Gunther S. Functional analysis of hepatitis B virus reactivating in hepatitis B surface antigen-negative individuals. HEPATOLOGY 2005;42: 93-103. 2. Manegold C, Hannoun C, Wywiol A, Dietrich M, Polywka S, Chiwakata CB, et al. Reactivation of hepatitis B virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy. Clin Infect Dis 2001;32:144-148. 3. Drosten C, Nippraschk T, Manegold C, Meisel H, Brixner V, Roth WK, et al. Prevalence of hepatitis B virus DNA in anti-HBc-positive/HBsAgnegative sera correlates with HCV but not HIV serostatus. J Clin Virol 2004;29:59-68.

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 μg/h+250 μg 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.