Eduardo Moitinho

Prognostic value of early measurements of portal pressure in acute variceal bleeding

BACKGROUND & AIMS Variceal bleeding is the most important complication of portal hypertension. However, the relationship between the increase in portal pressure and the outcome of variceal bleeding has not been well defined. METHODS We measured the hepatic venous pressure gradient (HVPG) of 65 cirrhotic patients with acute variceal hemorrhage, early after admission (20.6 +/- 15.6 hours). RESULTS Twenty-three patients had a poor evolution (failure to control bleeding or early variceal rebleeding), and 42 had an uneventful evolution. The only variable associated with outcome was the HVPG, which was higher in patients with a poor evolution (23.7 +/- 6.1 vs. 19.2 +/- 3.3 mm Hg; P < 0.0004). This was confirmed by multivariate analysis. HVPG was >/=20 mm Hg in 19 of 23 patients with poor evolution vs. 12 of 42 patients with uneventful evolution (P < 0.0001). An initial HVPG of >/=20 mm Hg was associated with a significantly longer intensive care unit stay (7 +/- 5 vs. 4 +/- 2 days; P < 0.02), longer hospital stay (19 +/- 10 vs. 14 +/- 6 days; P < 0.02), greater transfusion requirements (9.0 +/- 7.7 vs. 4.7 +/- 3.2 UU; P < 0.007), and a worse actuarial probability of survival (1-year mortality, 64% vs. 20%; P < 0.002). CONCLUSIONS Early measurement of HVPG in cirrhotic patients during acute variceal bleeding provides useful prognostic information on the evolution of the bleeding episode and long-term survival.

Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding

BACKGROUND/AIMS The dose of somatostatin used for variceal bleeding (250 microg/h) is lower than that proven to effectively decrease portal pressure and azygos blood flow (500 microg/h). Moreover, i.v. somatostatin boluses have greater effects than continuous infusions. The aim of this study was to investigate whether higher doses of somatostatin and repeated boluses may increase its efficacy in controlling variceal bleeding. METHODS A total of 174 patients with acute variceal bleeding were randomized to receive for 48 h: (A) one 250 microg bolus +250 microg/h infusion; (B) three 250 microg boluses +250 microg/h infusion; (C) three 250 microg boluses +500 microg/h infusion. RESULTS The three schedules of somatostatin were equally effective in controlling variceal bleeding (73, 75 and 81%, respectively, NS). Multivariate analysis showed active bleeding at endoscopy (n=75) as the only predictor of failure to control bleeding. In these patients, the 500 microg/h infusion dose achieved a higher rate of control of bleeding (82 vs. 60%, P<0.05), less transfusions (3.7 +/- 2.7 vs. 2.5 +/- 2.3 UU, P=0.07) and better survival (93 vs. 70%, P<0.05) than schedules A/B. CONCLUSIONS Somatostatin is highly effective in controlling variceal bleeding. Patients with active bleeding at emergency endoscopy may benefit from higher doses of somatostatin infusion.

Time profile of the haemodynamic effects of terlipressin in portal hypertension

BACKGROUND/AIMS Terlipressin is a long-acting vasopressin analogue that has been proved useful in the treatment of variceal haemorrhage. This study investigates the time profile of the haemodynamic effects of terlipressin on portal hypertension as well as the efficacy in decreasing portal-pressure and collateral blood flow of reduced doses, suitable for longer therapy to prevent early rebleeding. METHODS Splanchnic and systemic haemodynamics were measured in 23 patients with cirrhosis and portal hypertension in baseline conditions and at 30 min, 1, 2, 3 and/or 4 h after the double-blind administration of a single intravenous injection of 1 mg (n=8) or 2 mg (n=8) of terlipressin, or placebo (n=7). RESULTS Placebo caused no significant effects. At 30 min of terlipressin administration, the hepatic venous pressure gradient (1 mg: -16+/-9%, 2 mg: -21+/-11%; p<0.01) and azygos blood flow (1 mg: -19+/-13%, 2 mg: -25+/-17%; p<0.05) were significantly reduced. These effects were still significant at 4 h (2 mg) or 3 h (1 mg). Both doses moderately increased arterial pressure at 1 h. At 4 h, neither arterial pressure nor peripheral vascular resistance was significantly modified by either dose of terlipressin. Terlipressin caused no significant changes in hepatic blood flow. CONCLUSIONS In patients with cirrhosis, a single injection of 2 mg of terlipressin significantly and markedly reduces portal pressure and azygos blood flow for up to 4 h. The effects of a reduced dose (1 mg) were almost as pronounced and prolonged, suggesting that after the initial control of variceal bleeding, terlipressin therapy could be maintained for several days at low dosage to reduce the risk of early rebleeding.

The model for end-stage liver disease score is the best prognostic factor in human immunodeficiency virus 1-infected patients with end-stage liver disease: a prospective cohort study.

End‐stage liver disease (ESLD) has become the main cause of mortality in patients coinfected by human immunodeficiency virus (HIV) and hepatitis B virus or hepatitis C virus in developed countries. The aim of this study was to describe the natural history of and prognostic factors for ESLD, with particular attention paid to features affecting liver transplantation. This was a prospective cohort study in 2 Spanish community‐based hospitals performed between 1999 and 2004. One hundred four consecutive patients with cirrhosis and a first clinical decompensation of their chronic liver disease or hepatocellular carcinoma were included in the study. During a median follow‐up of 10 months (endpoint: death, liver transplantation, or the last checkup date), 61 patients (59%) died. The probability of mortality (Kaplan‐Meier method) at 1, 2, and 3 years was 43% [95% confidence interval (CI), 34%–60%], 59% (95% CI, 48%–70%), and 70% (95% Cl, 59%–81%), respectively. In a multivariate analysis, the Model for End‐Stage Liver Disease (MELD) score and the inability to reach an undetectable plasma HIV‐1 RNA viral load at any time during follow‐up were the only variables independently associated with the risk of death (P < 0.001). Fifteen (14%) of the 104 patients were accepted for liver transplantation, although only 5 underwent the procedure, and 10 died while on the waiting list. The waiting list mortality rate in patients with a MELD score < 20 and in patients with a MELD score >20 was 58% and 100%, respectively (median follow‐up, 5 months). In conclusion, HIV‐1–infected patients with ESLD, especially those with poorly controlled HIV and a high MELD score, have a poor short‐term outcome. The MELD score may be useful in deciding whether to indicate liver transplantation in these patients. However, because only a small proportion of the patients in this study were considered candidates for liver transplantation and most died while on the waiting list, few received a transplant. Liver Transpl 15:1133–1141, 2009.

Prevalence and prognostic value of hepatocellular carcinoma in cirrhotic patients presenting with spontaneous bacterial peritonitis

BACKGROUND/AIMS This study examined the prognostic power of hepatocellular carcinoma in patients presenting an episode of spontaneous bacterial peritonitis treated with 3rd generation cephalosporins or quinolones, and subsequent prophylaxis with norfloxacin until death or transplantation. METHODS The study comprises the prospective evaluation of 168 consecutive cirrhosis patients presenting an episode of spontaneous bacterial peritonitis. RESULTS Hepatocellular carcinoma was diagnosed in 35 out of the 168 (20%) patients included in the study (10 single; 25 advanced tumors). Renal impairment developed in 82 patients. Resolution of infection was achieved in 90% of the cases, the hospital survival being 70%. Renal impairment, advanced tumor stage, albumin, and GGT showed independent prognostic value for hospital mortality. At the end of follow-up 101 patients had died, the 1- and 2-year survival being 36% and 31%, respectively. Four variables independently predicted survival: advanced tumor (OR: 3.9; p=0.00001), renal impairment (OR: 2.1; p=0.00001), bilirubin (OR: 1.6; p=0.02) and creatinine (OR: 1.3; p=0.03). Advanced tumor retained independent predictability in patients surviving hospitalization (OR: 7.5; p=0.0001), the 6-month survival being significantly lower in patients with advanced tumor (12% vs 57%, p<0.00001). CONCLUSION The prevalence of hepatocellular carcinoma in cirrhotic patients with spontaneous bacterial peritonitis is high, and its presence should be actively sought. Advanced tumor impairs both hospital and long-term survival, and should be considered in the design of future trials.

Effects of increasing blood hemoglobin levels on systemic hemodynamics of acutely anemic cirrhotic patients

BACKGROUND/AIMS In experimental portal hypertension, blood hemoglobin levels have been shown to influence the hyperdynamic circulatory state. The aim of this study was to assess the hemodynamic effects of increasing hemoglobin concentration in human portal hypertension. METHODS Sixteen cirrhotic patients recovering from a variceal bleeding episode were randomly assigned to receive two units of packed red cells or 500 ml of a protein solution. Systemic and portal hemodynamics, and rheological and hormonal parameters were measured at baseline and after expansion. RESULTS Both groups were similar with respect to the degree of liver failure, severity of the bleeding episode, activation of the endogenous vasopressor systems, and hemodynamic parameters. The administration of either erythrocytes or a protein solution prompted a similar increase in total blood volume and suppression of vasopressor systems. Both groups of patients experienced similar increases in wedged hepatic venous pressure. Hepatic venous pressure gradient was not significantly modified but tended to increase in erythrocyte-transfused patients. Cardiopulmonary pressures increased, but this increment was significant in the non-blood-transfused patients only. Cardiac output decreased in erythrocyte-transfused patients, while it increased in the group receiving a protein solution. Red blood cell transfusion resulted in an increase in systemic vascular hindrance (resistance/blood viscosity), whereas the administration of a protein solution prompted a decrease in this parameter, thus reflecting true vasoconstriction and vasodilation, respectively. CONCLUSIONS An increase in blood hemoglobin in acutely anemic cirrhotic patients attenuates their hyperdynamic circulation beyond viscosity-dependent changes, an effect which might be counteracted by the effects on portal venous pressure gradient.

Reversible oral-facial dyskinesia in a patient receiving ciprofloxacin hydrochloride

12.Ono S, Munakata S, Nagao K, Schimizu N, Schimizu N (1989) The syndrome of continuous muscle fiber activity: light and electron microscopic studies in muscle and nerve biopsies. J Neurol 236 : 377-381 13. Valli G, Barbieri S, Cappa S, Pellegrin G, Scarlato G (1983) Syndromes of abnormal motor activity: overlap between continuous muscle fiber activity and the stiff man syndrome. J Neurol Neurosurg Psychiatry 46 : 241-247 14. Wallis W, Poznak AV, Plum F (1970) Generalized muscular stiffness, fasciculations and myokymia of peripheral nerve origin. Arch Neurol 22:430439 15. Warmonlts JR, Mendell JR (1980) Neurotonia: impulse induced repetitive discharges in motor nerves in peripheral neuropathy. Ann Neurol 7 : 245250 16. Welsh LK, Appenzeller O, Bicknell JM (1972) Peripheral neuropathy with myokymia, sustained muscular contraction, and continuous motor unit activity. Neurology 22:161-169 17. Yokota T, Saito Y, Miyatake T (1994) Conduction slowing without conduction block of compound muscle and nerve action potential due to sodium channel block. J Neurol Sci 124:220224

Propranolol plus molsidomine vs propranolol alone in the treatment of portal hypertension in patients with cirrhosis

BACKGROUND/AIMS Effective protection from the risk of variceal bleeding is achieved when the hepatic venous pressure gradient is reduced to 12 mmHg or at least by 20% of baseline values. Such a marked decrease is rarely achieved with propranolol, and new agents or combinations of them are now being explored. The present randomized study investigated whether chronic treatment with the combination of propranolol plus molsidomine, a preferential venous dialator that reduces hepatic venous pressure gradient and does not cause pharmacological tolerance, achieves greater reduction in hepatic venous pressure gradient than propranolol alone. METHODS A hemodynamic study was performed in 34 patients with cirrhosis with portal hypertension in baseline conditions and after 3 months of chronic oral treatment with propranolol alone (n = 19) or propranolol plus molsidomine (n = 15). RESULTS Propranolol produced a significant reduction in hepatic venous pressure gradient (-16%, p < 0.01). Propranolol plus molsidomine also caused a slight but significant decrease in hepatic venous pressure gradient (-9%, p < 0.05). Hepatic blood flow and the hepatic and intrinsic clearance of indocyanine green were significantly reduced by propranolol. The combined administration of propranolol+molsidomine significantly reduced hepatic blood flow but not hepatic and intrinsic clearance of indocyanine green. Both treatment groups produced similar reduction in azygos blood flow, heart rate and cardiac output. However, contrary to propranolol alone, propranolol plus molsidomine did not increase cardiopulmonary pressures. CONCLUSIONS The current study shows that although the combined administration of propranolol plus molsidomine prevents some of the adverse effects of propranolol on liver function and cardiopulmonary pressures, it does not achieve a greater reduction in hepatic venous pressure gradient than propranolol alone and therefore, does not support the use of this combined therapy for the pharmacological treatment of portal hypertension.

Randomized comparison of long-term Losartan vs propranolol in lowering portal pressure in cirrhosis

BACKGROUND & AIMS It has been suggested that losartan, an angiotensin II (A-II) type 1 receptor blocker, may have a pronounced portal pressure reducing effect, far greater than that of propranolol. This randomized controlled trial compared the hemodynamic and renal effects of continued 6-week administration of losartan (n = 25) vs. propranolol (n = 15) in portal hypertensive patients with cirrhosis treated endoscopically after a variceal bleeding episode. METHODS Hepatic venous pressure gradient (HVPG), systemic hemodynamics, renal function, and vasoactive factors were measured before and at 6 weeks of treatment. RESULTS Losartan did not reduce HVPG (-2% +/- 12%, NS) but significantly decreased mean arterial pressure (MAP, -8% +/- 10%, P = 0.001). On the contrary, propranolol significantly reduced HVPG (-10% +/- 11%, P = 0.003) and cardiac output (-16% +/- 12%, P = 0.001) but did not modify MAP (2.5% +/- 10%, NS). Losartan increased A-II levels, reduced aldosterone, and decreased glomerular filtration rate (GFR) in Child B patients. Propranolol did not modify renal function. Adverse events related to therapy were mild and similar in both groups. CONCLUSIONS Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patients with moderate liver failure. Therefore, losartan is not an alternative to propranolol in preventing variceal rebleeding.