A randomized controlled trial of acarbose in hepatic encephalopathy

doi:10.1016/S1542-3565(04)00667-6

Clinical Gastroenterology and Hepatology

Volume 3, Issue 2, February 2005, Pages 184-191

https://doi.org/10.1016/S1542-3565(04)00667-6 Get rights and content

Background & aims: Hepatic encephalopathy in cirrhosis is contributed to by toxic products deriving from the proteolytic bacterial flora–related degradation of dietary nitrogen substances. Acarbose is a novel hypoglycemic agent acting through the inhibition of glucose absorption in the gut and the promotion of intestinal saccharolytic bacterial flora at the expense of proteolytic flora. We assessed whether acarbose exerts a beneficial effect on hepatic encephalopathy and on postprandial hyperglycemia in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus. Methods: One hundred seven cirrhotic patients with grade 1–2 hepatic encephalopathy and type 2 diabetes mellitus were randomized to acarbose 100 mg 3 times daily or placebo for 8 weeks; after a 2-week washout period, treatments were switched, and patients were followed for 8 more weeks. Ammonia blood levels, Reitan’s number connection test, intellectual function, fasting and postprandial glucose levels, glycated hemoglobin values, and C peptide values were determined 2 weeks before and 4, 8, 11, 14, and 18 weeks after treatment. Results: (1) Acarbose significantly decreased ammonia blood levels and improved Reitan’s test score and intellectual function score compared with placebo (P < .01). (2) Acarbose caused a 33% decrease in fasting glucose level and an approximately 50% decrease in postprandial glucose level compared with placebo (P < .01). (3) Acarbose significantly lowered glycated hemoglobin values and postprandial C peptide compared with baseline values, whereas placebo did not. (4) No change in biochemical parameters of liver function was observed after acarbose treatment. Conclusions: Acarbose is a safe and effective drug in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus.

Section snippets

Patients and methods

All patients gave their written informed consent to enter the study, which was conducted according to the Declaration of Helsinki and after approval by the local Ethical Committee.

Results

After randomization, 55 patients were initially treated with acarbose, and 52 patients were initially treated with placebo. No dropouts were observed during the study, and all the patients had stable liver function, evaluated according to Child–Pugh score.27 No adverse events or complications caused by cirrhosis or side effects caused by treatments occurred during the study.

Discussion

Acarbose is a novel hypoglycemic agent that acts by inhibiting gastrointestinal α-glucosidase activities, the enzymatic system responsible for glucose absorption in the gastrointestinal tract. We studied whether acarbose exerted any effect on ammonia blood levels, HE, and postprandial hyperglycemia in cirrhotic patients with grade 1–2 HE and type 2 diabetes. Acarbose was significantly superior to placebo in decreasing ammonia blood levels, causing a 52.6% ± 9.4% decrease compared with baseline

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Citation Excerpt :
Another advantage of AGI is that they may have a beneficial effect in hepatic encephalopathy by decreasing proteolytic flora (which increase NH3 levels) & increasing saccharolytic flora besides having a laxative effect, which may contribute to the improvement of hepatic encephalopathy. In a study of acarbose in patients with low-grade hepatic encephalopathy and diabetes mellitus, besides improvement in glycemic control, treatment with acarbose resulted in a decrease in blood ammonia levels and hepatic encephalopathy.116 While there are rare reports of acarbose-induced hepatotoxicity,117–119 AGI has low systemic absorption and hepatic metabolism and are considered to be safe in patients with cirrhosis.120
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
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: Supported by a grant from the Italian Ministry of University and Scientific and Technological Research and, in part, by a special grant from the Italian Association for Diabetes (AID-Stabia, Castellammare di Stabia, Naples, Italy).

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Original articlesA randomized controlled trial of acarbose in hepatic encephalopathy

Section snippets

Patients and methods

Results

Discussion

Gastroenterology

Diabetes Res Clin Pract

Diabetes Res Clin Pract

Gastroenterology

J Hepatol

Lancet

Pathogenesis and treatment of portal-systemic encephalopathyan update

Dig Dis Sci

Pathophysiology of hepatic encephalopathy

Hepatogastroenterology

Blood and brain concentrations of mercaptans in hepatic and metanethiol induced coma

Gut

Theoretic therapy of hepatic encephalopathy

Protein load induced ureogenesis and ammoniogenesis in patients with non-alcoholic liver cirrhosis

Increased intestinal hydrolysis of urea in patients with alcoholic cirrhosis

Scand J Gastroenterol

Treatment of hepatic encephalopathy with non-absorbable antibiotics

Ital J Gastroenterol

Lactobacillus acidophilus (empac) in the treatment of hepatic encephalopathy

Br Med J

Der Diabetes mellitus

Study on the carbohydrate metabolism in chronic infectious hepatitis

Arch Intern

Liver diseases and diabetes mellitus

Glucose tolerance and diabetes mellitus in chronic liver disease

Lancet

Liver disease and diabetes mellitus

Diabetes Rev

Glibenclamide associated reversible cholestasis

Eur J Med

Effect of treatment with acarbose and insulin in patients with non-insulin-dependent diabetes mellitus associated with non-alcoholic liver cirrhosis

Diabetes Obes Metab

Original articles
A randomized controlled trial of acarbose in hepatic encephalopathy