Predictors of nonresponse to lactulose in patients with cirrhosis and hepatic encephalopathy

Lactulose is commonly used in the treatment of hepatic encephalopathy (HE). However, all patients do not respond to lactulose. We evaluated predictors of nonresponse to lactulose in patients with cirrhosis and HE.

Consecutive cirrhotic patients with HE were enrolled. HE was diagnosed by West Haven criteria. Patients were treated with lactulose and correction of any associated precipitating factors. Nonresponse was defined if patient remained in HE even after 10 days of treatment or died while in HE.

Of 300 patients with cirrhosis and HE, 231 (77%) patients met the inclusion criteria. The majority (95%) of the patients had Grade 2 or 3 HE. Of 231 patients, 180 (78%) responded to lactulose. Fifty-one (22%) did not respond to lactulose, 34 (15%) died without any improvement in HE and HE did not improve in 17 (7%) patients after 10 days of therapy. On comparing baseline parameters between nonresponders versus responders there was significant difference between baseline age (42.0+/-11.9 vs. 46.6+/-12.7 year, P=0.02), total leukocyte count (median, 9300 vs. 7300 cells/mm3, P=0.001), serum sodium level (129.9+/-6.2 vs. 133.7+/-7.1 mmol/l, P=0.001), model for end stage liver disease (MELD) score (22.9+/-3.8 vs. 19.9+/-4.2, P=0.001), mean arterial pressure (MAP, 77.9+/-10.0 vs. 86.3+/-8.7 mmHg, P=0.001), serum AST (median, 114 vs. 76 IU/l, P=0.01), serum ALT (median, 84 vs. 48.5 IU/l, P=0.001), spontaneous bacterial peritonitis [18 (35%) vs. 37 (21%), P=0.02] and hepatocellular carcinoma [HCC, 17 (33%) vs. 14 (7%), P=0.001]. On multivariate analysis baseline total leukocyte count, MELD, MAP, and HCC were independent predictors of nonresponse to lactulose (P=0.001). Combination of low MAP, high MELD, and presence of HCC had diagnostic accuracy of 81% in predicting nonresponse to lactulose.

Of 78% patients with chronic liver disease with HE (majority with Grade 2 and 3) responded to lactulose. High baseline MELD, high total leukocyte count, low serum sodium, low MAP, and presence of hepatocellular carcinoma were predictors of nonresponse to lactulose.