Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta-blockers: a randomized trial of ligation.

AIM: To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to beta-blockers for prevention of first bleeding in portal hypertension. METHODS: A sample size of 214 was planned with all sizes of varices. However, the trial was stopped due to increased bleeding in 52 patients in the ligation group. The baseline severity liver disease and endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 +/- 9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 +/- 10.27). RESULTS: The mean follow-up period was 19.5 +/- 13.3 months: five bled in the ligation group (20%), three from varices (two after banding at 11 and 17 days; one during the procedure), and two from gastropathy; two bled in the not-treated group (7%- two both varices) (P = 0.24). There were seven deaths in the ligation group and 11 in the not-treated group (P = 0.39). CONCLUSION: Sixty per cent of the bleeding in the banding group was probably iatrogenic, requiring the study to be stopped. Endoscopic banding ligation was no better than no treatment. This study suggests that ligation may be harmful when used as primary prophylaxis, similar to prophylactic sclerotherapy in the past.

Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis.

BACKGROUND: Endotoxaemia is commonly seen in cirrhotic patients with ascites and this may be associated with increased portal pressure. AIM: To investigate the effect of intestinal decontamination on liver haemodynamics in alcohol-related cirrhotic patients with ascites. METHODS: We included 30 patients. At day 0, systemic and splanchnic circulation endotoxin levels were determined and HVPG measurement performed. Patients received rifaximin (1200 mg/day) for 28 days. At day 29, systemic and splanchnic circulation endotoxin levels were determined and HVPG measurement performed again. RESULTS: Median (range) plasma endotoxin levels decreased significantly after rifaximin administration both in systemic [1.45(0-3.1) vs. 0.7(0-2.7), P < 0.0001] and splanchnic circulation [1.8(0-3.4) vs. 0.8(0-2.1), P < 0.0001]. Meanwhile, the difference seen in endotoxin levels between the splanchnic and systemic circulation at day 0 (P = 0.001) was not noted at day 29 (P = 0.137). HVPG measurement was possible in 28 patients. Median (range) HVPG values were 18 mmHg (12.7-26.3) on day 0 vs. 14.7 mmHg (7-20) on day 29 (P < 0.0001). HVPG decreased after rifaximin in 23, remained stable in two and increased in three patients. CONCLUSION: Hepatic venous pressure gradient values decreased significantly after intestinal decontamination with rifaximin in patients with alcohol-related decompensated cirrhosis and this might have been achieved through significant reduction of plasma endotoxin levels.

Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine.

BACKGROUND: The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation. AIM: To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants. METHODS: Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy. RESULTS: The median follow-up after adefovir's onset was 31 (18-40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <10(4) copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months. CONCLUSION: In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.

Clinical trial: The effect of somatostatin vs. octreotide in preventing post-endoscopic increase in hepatic venous pressure gradient in cirrhotics with bleeding varices.

BACKGROUND: Hepatic venous pressure gradient (HVPG) increases significantly after endoscopic therapy in patients with bleeding oesophageal varices, which may precipitate further haemorrhage. Whether vasoactive drugs can suppress these changes remains unknown. AIM: To investigate the efficacy of somatostatin when compared with octreotide in preventing the post-endoscopic increase in HVPG during acute bleeding and whether the changes affect outcome. METHODS: Thirty-three cirrhotics with bleeding varices were randomized to receive somatostatin (n = 17) or octreotide (n = 16) under double-blind conditions, soon after their admission. HVPG measurements were performed before and immediately after endoscopic treatment. RESULTS: In the somatostatin group, postendotherapy HVPG values did not change significantly when compared with pre-treatment values (18.9 vs. 17.2, P = 0.092). Conversely, in the octreotide group, HVPG increased significantly after endoscopy (18.2 vs. 20.8, P = 0.003). The probability of 6-week survival without treatment failure was significantly higher in the somatostatin group (P = 0.024). Post-endoscopic HVPG value was independently associated with 6-week failure. CONCLUSIONS: Somatostatin, but not octreotide, effectively prevents the post-endoscopic increase in HVPG, which may be associated with low probability of treatment failure.