1. clinicaloptions.com/hepatitis HALT-C: Long-term Maintenance Peginterferon alfa-2a Slideset on: Sharma BC, Sharma P, Agrawal A, Sarin SK. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137:885-891. Lactulose Secondary Prophylaxis Effective for Preventing Recurrence of Hepatic Encephalopathy in Patients With Cirrhosis This program is supported by educational grants from

2. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Background and Rationale  Minimal and overt HE common sequelae of advanced liver disease –Poor probability of survival after HE onset  Primary treatment of HE involves treatment of precipitating factors –Most medications primarily directed at reducing/eliminating a variety of small molecules including those that contribute to neurotoxic ammonia levels –Nonabsorbable disaccharides (eg, lactulose, lactitol) preferred for eliminating bacterial flora  Current study assessed efficacy of lactulose for prevention of HE recurrence following recovery from preceding episode of overt HE Sharma BC, et al. Gastroenterol. 2009;137:885-891.

3. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Schematic of Study Design Sharma BC, et al. Gastroenterol. 2009;137:885-891. Cirrhotic patients who had recovered from HE episode* (N = 140) Lactulose 30-60 mL given in 2-3 divided doses to yield 2-3 semisoft stools/day † (n = 70) No Lactulose † (n = 70) End of treatment: primary endpoint or minimum follow-up of 6 mos *Patients randomized to lactulose or no lactulose within 1 wk of HE recovery; 1-wk period chosen to prevent early HE recurrence following cessation of lactulose and antibiotics. † Additional therapy for all patients included previous treatment and secondary prophylaxis of variceal bleed, if necessary.

4. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Main Findings  High prevalence of abnormal psychometry test results and abnormal CFF test results at baseline –Patients with ≥ 2 abnormal psychometry test results had significantly lower CFF results vs those with < 2 abnormal psychometry results (37.1 vs 41.7 Hz; P =.001) –No difference in CFF scores for patients who developed HE vs those who did not (36.6 vs 38.6 Hz; P =.11) Psychometric and CFF Tests Abnormal Test Results, % Lactulose (n = 70) No Lactulose (n = 70) NCT-A6570 NCT-B6065 FCT-A71 FCT-B71 Digit symbol test6575 Object assembly test8575 CFF55 Sharma BC, et al. Gastroenterol. 2009;137:885-891.

5. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Main Findings  Significantly more patients not taking prophylactic lactulose developed HE compared with those receiving prophylactic lactulose in per protocol analysis (46.8% vs 19.6%; P =.001) Outcome, n (%)Lactulose (n = 61) No Lactulose (n = 64) P Value Development of HE12 (19.6)30 (46.8).001  Grade 100  Grade 26 (50)16 (53)  Grade 33 (25)8 (27)  Grade 43 (25)6 (20)  Currently taking beta-blockers2 (17)8 (27).09 HE precipitating factor(n = 12)(n = 30)  Infections5 (42)16 (53).01  Variceal bleed3 (25)4 (13) NG  Constipation0 (0)4 (13) NG  Unknown4 (33)6 (20).29 Death5 (8)11 (17).18 Sharma BC, et al. Gastroenterol. 2009;137:885-891.

6. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Main Findings  ≥ 2 abnormal psychometric test results observed in 26% of patients receiving lactulose and 57.6% of patients not receiving lactulose –Recurrence of overt HE significantly associated with ≥ 2 abnormal psychometric test results following recovery of preceding HE episode –Pearson’s coefficient (r): 0.369 (P =.02) –No association found between development of HE and baseline values for Child’s score, ammonia level, CFF, or MELD score Sharma BC, et al. Gastroenterol. 2009;137:885-891.

7. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Other Outcomes  Rate of hospital readmission due to causes other than HE similar between groups Sharma BC, et al. Gastroenterol. 2009;137:885-891. Hospital Readmissions Other Than HE Lactulose (n = 61) No Lactulose (n = 64) Total, n (%)9 (14.7)6 (9.3)  SBP, n32  Urinary tract infection, n31  Pneumonia, n21  Upper gastrointestinal bleed, n12

8. clinicaloptions.com/hepatitis Lactulose Secondary Prophylaxis for Hepatic Encephalopathy Recurrence Summary of Key Conclusions  Prophylactic treatment with lactulose following an episode of HE in cirrhotic patients significantly decreased incidence of HE recurrence compared with no lactulose prophylaxis –Infections more common as precipitating factors for HE recurrence among patients not on lactulose vs those on lactulose  Presence of ≥ 2 abnormal psychometric test(s) results after recovery from initial HE episode significantly associated with HE recurrence Sharma BC, et al. Gastroenterol. 2009;137:885-891.