Michalis Economou

The Effects of Chronic Treatment with Octreotide versus Octreotide plus Midodrine on Systemic Hemodynamics and Renal Hemodynamics and Function in Nonazotemic Cirrhotic Patients with Ascites

OBJECTIVES:The adrenergic agonist midodrine improved circulatory and renal dysfunction when acutely administered in nonazotemic cirrhotic patients with ascites while its combination with octreotide has recently been proposed as an effective treatment of type 1 hepatorenal syndrome (HRS). However, the effects of octreotide on systemic hemodynamics and renal function in cirrhotic patients are controversial. This study evaluated the effects of chronic treatment with octreotide versus octreotide plus midodrine on systemic hemodynamics and renal hemodynamics, and function in nonazotemic cirrhotic patients with ascites.METHODS:Twenty-five patients were studied at baseline and 11 days after administration of subcutaneous octreotide 300 μg, b.i.d. alone (n = 12) or together with oral midodrine 7.5 mg, t.i.d. (n = 13).RESULTS:Octreotide did not improve systemic hemodynamics whereas the addition of midodrine significantly decreased cardiac index (CI) and heart rate (HR), and increased mean arterial pressure (MAP) and systemic vascular resistance (SVR). Octreotide caused a decrease in renal vascular resistance (RVR) and increased renal blood flow (RBF) but significantly reduced glomerular filtration rate. The association of midodrine to octreotide did not modify renal hemodynamics and function as compared to baseline while it caused an almost significant minor increase in RVR and a significant minor decrease in RBF as compared to octreotide alone. Consequently, a significant minor increase in glomerular filtration rate was demonstrated. The plasma values of active renin, aldosterone, and glucagon were significantly reduced in either group.CONCLUSIONS:Octreotide does not improve systemic hemodynamics in nonazotemic cirrhotic patients with ascites while it impairs renal function. On the other hand, the addition of midodrine can ameliorate the hyperdynamic circulation without inducing renal dysfunction in these patients.

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.

Effects of somatostatin, terlipressin and somatostatin plus terlipressin on portal and systemic hemodynamics and renal sodium excretion in patients with cirrhosis.

Background and Aim:  Terlipressin and somatostatin are the most preferable agents for the control of variceal bleeding in cirrhotic patients. The present study evaluated the hemodynamic effects of somatostatin, terlipressin and somatostatin plus terlipressin in cirrhotic patients with portal hypertension, as well as the effect of each regimen on renal sodium excretion.

The effects of treatment with octreotide, diuretics, or both on portal hemodynamics in nonazotemic cirrhotic patients with ascites.

Goals To evaluate the effects of diuretic treatment, octreotide, or both on portal hemodynamics in nonazotemic cirrhotic patients with ascites. Background Diuretics and octreotide have been associated with a decrease in portal pressure in cirrhotic patients, suggested to be mediated by plasma volume depletion and splanchnic vasoconstriction, respectively. However, liver cirrhosis is characterized by activation of the renin-angiotensin-aldosterone axis, which increases hepatic vascular resistance and is augmented or suppressed by diuretics or octreotide, respectively. Study Twenty nonazotemic cirrhotic patients with ascites were treated with furosemide and spironolactone. Of them, 10 (group 1) discontinued diuretic treatment for 7 days. Thereafter for 5 days, each patient received subcutaneous octreotide, 300 μg twice per day; ten of them (group 2) received the octreotide in addition to their usual diuretic treatment. Portal and systemic hemodynamics with Doppler ultrasound and endogenous vasoactive systems were evaluated while the patients received diuretics (both groups), after discontinuation of diuretics (group 1), and after octreotide administration (both groups). Results The withdrawal of diuretics did not alter portal hemodynamics, but it impaired systemic hemodynamics and suppressed the renin-aldosterone axis. The addition of octreotide to diuretic treatment but not octreotide alone improved portal and systemic hemodynamics. In both groups the initiation of octreotide administration suppressed the renin-aldosterone axis and plasma glucagon levels. Conclusions In nonazotemic cirrhotic patients with ascites, the combination of diuretics and octreotide improves systemic hemodynamics and inhibits the diuretic-related component of the activated renin-aldosterone axis, which in turn augments the portal hypotensive effect of diuretic-induced plasma volume depletion.

CASE REPORT: Toxic Hepatitis After Sequential Administration of Flutamide and Cyproterone Acetate

Flutamide and cyproterone acetate are representatives of the two different classes of androgen receptor antagonists which are commonly used in the treatment of prostatic cancer. Flutamide belongs to the so–called pure, nonsteroidal antiandrogens and cyproterone acetate is classified as a steroidal antiandrogens. A variety of hepatotoxic reactions has been reported with flutamide and also with cyproterone acetate (5–16). Clinical pictures range from weakness and anorexia to the symptoms and signs of fulminant hepatic failure and death. Therefore, close monitoring is recommended during treatment periods, and in cases of hepatic toxicity it is usually the practice to turn to the drug of the other class. Herein we report the observation of toxic hepatitis with severe hepatocellular dysfunction after the sequential administration of a nonsteroidal and a steroidal antiandrogen in a patient taking flutamide and, after a few months, cyproterone acetate. The risk for toxic hepatitis development after sequential administration of two different androgen receptor antagonists is not well known. Our observation raises arguments against the practice of starting treatment with one agent when the other has to be discontinued due to hepatoxicity

Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.

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

Abstract: 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.