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Biomedical subjects

L Dagher

Publications and source records attributed to L Dagher.

10 recordsLinked to original sources

Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?

Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.

Antiviral Agents↗

Variceal bleeding and portal hypertensive gastropathy.

Cirrhosis can be the end stage of any chronic liver disease. At the time of diagnosis of cirrhosis varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, large size of varices and the presence of endoscopic red colour signs but only one-third of patients who have variceal haemorrhage have the above risk factors. Recent interest has been directed at identifying haemodynamic factors that may reflect the pathophysiological changes which lead to variceal bleeding, e.g. it has been confirmed that no bleeding occurs if HVPG falls below 12 mmHg and also a hypothesis has been put forward in which bacterial infection is considered a trigger for bleeding. Pharmacological treatment with beta-blockers is safe, effective and is the standard long-term treatment for the prevention of recurrence of variceal bleeding. Combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for reduction in HVPG response needs further study, and surrogate markers of pressure response need evaluation. If endoscopic treatment is chosen, variceal ligation is the modality of choice. The combination of simultaneous variceal ligation and sclerotherapy does not offer any benefit. However, the use of additional sclerotherapy for the complete eradication of small varices after variceal ligation needs to be evaluated. The results of current prospective randomized controlled trials comparing variceal ligation with pharmacological treatment are awaited with great interest. Finally, the use of transjugular intrahepatic portosystemic shunt (TIPS) for the secondary prevention of variceal bleeding is not substantiated by current data, as survival is not improved and because of its worse cost-benefit profile compared to other treatments. In contrast, there still is a role for the selective surgical shunts in the modern management of portal hypertension. The ideal patients should be well compensated cirrhotics, who have had troublesome bleeding - either who have failed at least one other modality of therapy (drugs or ligation), have bled from gastric varices despite medical or endoscopic therapy, or live far from suitable medical services. Recently, ligation has been compared to beta-blockers for primary prophylaxis but so far there is no good evidence to recommend banding for primary prophylaxis, if beta-blockers can be given.

Adrenergic beta-Antagonists↗

Review article: pharmacological treatment of the hepatorenal syndrome in cirrhotic patients.

Renal failure is common in patients who are dying from end-stage cirrhosis, developing in 40-80% of all patients. Where there is no anatomical or pathological cause for the renal failure, it is termed the hepatorenal syndrome. When the hepatorenal syndrome develops, it will only recover when there is some degree of improvement in liver function. Thus for most patients this will occur only after liver transplantation, although the transplantation mortality is increased in this group. Hepatorenal syndrome is a common complication of alcoholic hepatitis, and this group is unusual in that with time and abstinence, significant recovery of liver function may occur. There is therefore a need for supportive therapy to allow time for some recovery of liver function in patients with alcoholic hepatitis and hepatorenal syndrome. Similarly, patients may need support whilst waiting for liver transplantation. This article reviews the pathophysiology and treatment of hepatorenal syndrome.

Disease Progression↗

Drug treatment for bleeding oesophageal varices.

At the time of diagnosis of cirrhosis, varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, a large size of the varices and the presence of endoscopic red colour signs, but only a third of patients who suffer variceal haemorrhage demonstrate the above risk factors. The only treatment that does not require sophisticated equipment or the skills of a specialist, and is immediately available, is vasoactive drug therapy. Hence, drug therapy should be considered to be the initial treatment of choice and can be administered while the patient is transferred to hospital, as has been done in one recent study. Moreover, drug therapy is no longer considered to be only a 'stop-gap' therapy until definitive endoscopic therapy is performed. Several recent trials have reported an efficacy similar to that of emergency sclerotherapy in the control of variceal bleeding. Furthermore, recent evidence suggests that those patients with high variceal or portal pressure are likely to continue to bleed or re-bleed early, implying that prolonged therapy lowering the portal pressure over several days may be the optimal treatment. Pharmacological treatment with beta-blockers is safe, effective and the standard long-term treatment for the prevention of recurrence of variceal bleeding. The combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for the reduction of the HVPG response needs further study, and surrogate markers of the pressure response need evaluation. Ligation has recently been compared with beta-blockers for primary prophylaxis, but there is as yet no good evidence to recommend banding for primary prophylaxis if beta-blockers can be given.

Acute Disease↗

Management of oesophageal varices.

Beta-blockers are the treatment of choice to prevent the first episode of variceal bleeding and further rebleeding episodes. In acute bleeding all patients should receive pharmacological treatment with vasoconstrictors and endoscopic treatment. Failure of therapy should lead to consideration of transjugular intrahepatic portosystemic shunting.

Adrenergic beta-Antagonists↗

Acute jaundice.

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Acute Disease↗