231 Long-term aggressive nutritional therapy by the enteral or oral route in patients with alcoholic cirrhosis is supported by studies that have shown improved nutritional status.232, 233 Although controversial, this may possibly prevent complications of cirrhosis.195, 234 Multiple feedings, emphasizing breakfast and a nighttime snack, with a regular oral diet at higher-than-usual PD0325901 chemical structure dietary intakes (1.2-1.5 g/kg for protein and 35-40 kcal/kg for energy)

seem beneficial.235, 236 Finally, during intermittent acute illness or exacerbations of the underlying chronic liver disease, above normal protein intake (1.5 g/kg body weight), and kilocalorie intake (40 kcal/kg) improves protein calorie malnutrition,234 and should be considered in the treatment of these patients. Recommendation: 13. Patients with alcoholic cirrhosis should receive frequent interval feedings, emphasizing a night time snack and morning feeding, to improve nitrogen balance (Class I, level A). A number of other agents have been tested in patients with ALD. These include PTU, which was thought to decrease the hypermetabolic state induced by alcohol.237, 238 A Cochrane review of 6 randomized controlled trials of PTU in alcoholic liver disease,

with a total Epigenetics Compound Library of 710 patients administered either PTU or placebo did not show any benefit of PTU over placebo on the total or liver related mortality, complications of liver disease or liver histology in patients with alcoholic liver disease.239 A possible benefit of supplementation with S-adenosyl L-methionine (SAMe), a precursor to glutathione, has also been studied extensively.240 One

trial demonstrated a O-methylated flavonoid statistically significant improvement in survival in patients with Childs A and B cirrhosis randomized to SAMe compared to placebo.241 Despite a strong theoretical rationale, and a number of supportive clinical trials,240, 242 a Cochrane review of published data, based on nine randomized controlled trials with 434 patients in different stages of ALD, did not demonstrate any significant benefit of SAMe on total mortality, liver related mortality, complications or liver transplantation in patients with ALD.243 Colchicine, which has both anti-inflammatory and antifibrotic properties, has also been tested in alcoholic cirrhosis after several small clinical trials, had suggested improvement in fibrosis on serial liver biopsies in treated patients.244, 245 However, a systematic meta analysis by the Cochrane group of 15 randomized trials with 1714 patients (including patients with alcoholic fibrosis, alcoholic hepatitis, and/or alcoholic cirrhosis as well as patients with viral induced or cryptogenic fibrosis and/or cirrhosis)246 showed no benefit of treatment on overall mortality, liver related mortality, liver tests or histology. In addition, there was an increased risk of adverse effects related to colchicine therapy.