5 lacerda liver disease

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5 lacerda liver disease

  1. 1. Breakthrough Papers inHepatology in 2011GI Hepatology Update 2012Marco Lacerda
  2. 2. GENERAL HEPATOLOGY
  3. 3. • Individuals with PSC and UC are at higher risk for colorectal neoplasia• Retrospective studies have shown mixed results• High-dose UDCA (28-30) increased SAE in PSC
  4. 4. High-dose UDCA and coloncancer• Methods: • Patients with UC/PSC previously enrolled in a high dose UDCS trial were analyzed • 56 patients; 25 UDCA; 31 placebo • Mean time – 4.4 y • Results of surveillance colonoscopy and pathology analyzed
  5. 5. High-dose UDCA and coloncancer• Results • 9 of 25 (36%) of UDCA patients developed neoplasia (1 ca, 1 high-grade, 7 low-grade) • 3 of 31 (9.7%) of placebo patients developed neoplasia (1 ca, 1 high grade, 1 low grade) • Hazard risk 4.4; p=0.02
  6. 6. High-dose UDCA and coloncancer• Conclusion• Long term use of high-dose UDCA in patients with PSC/UC is associated with increased risk of colorectal neoplasia
  7. 7. • Although ¼ of patients with cirrhosis develop PVT, best treatment option is not clear;• Anticoagulation advocated for recent clots;• Small studies suggested efficacy of TIPS
  8. 8. TIPS for Portal vein thrombosis• Retrospective study of cirrhotic patients with non-tumoral PVTs receiving TIPS;• No anticoagulation was used.• 70 patients (67% males, mean age 55)• Mean Child’s score: 7.9; MELD 11.6;• Hepatitis C – 53%;• Decompensated portal hypertension was the indication in 94%
  9. 9. TIPS for Portal vein thrombosis• At mean f/u of 24 mo: • 57% had complete recanalization; • 30% had decreased thrombosis; • 13% had no improvement.• Of the patients with complete recanalization 97% maintained it for mean of 20.7 mo;• Survival: • 99% 1 mo • 89% 12 mo • 81% 24 mo
  10. 10. TIPS for Portal vein thrombosis• Conclusion: • For non-tumoral PVT TIPS was safe and effective in > 50% for at least 2 years;• Concerns: • No control group • Relatively small group
  11. 11. • Steroids are treatment of choice for severe ETOH hepatitis; however:• 6 mo mortality approaches 65%
  12. 12. Steroids plus NAC in severe ETOH hepatitis • Objectives and method • 6 months survival of 174 patients with severe ETOH hepatitis (Maddrey >32), randomized to receive steroids with or without NAC • All patients received 40 mg prednisone 28 d; • NAC group received IV infusion for initial 5 d
  13. 13. Steroids plus NAC in severe ETOH hepatitis • Conclusion: • Improved one month survival and development of HRS however; • No improvement in primary outcome – overall survival at 6 months
  14. 14. Early liver transplantation forsevere alcoholic hepatitis• Studied the result of early OLT (<6 mo sobriety) on 6 months survival of patients with severe alcoholic hepatitis• Admission criteria were • Maddrey >32; • No prior episodes of alcoholic hepatitis; • Non-response to medical therapy (Lille >0.45); • Adequate family support • No psychiatric co-morbidities and strong commitment
  15. 15. Early liver transplantation forsevere alcoholic hepatitis • 26 patients • Mean Lille score 0.88 • Mean non-response time 13 days • Fewer than 2% of admitted patients were selected • 2.9% of grafts were used
  16. 16. Results• 26 patients. 6 mo survival was higher than matched, non-randomized 26 controls (77 vs 23%, p<0.001)• 3 patients resumed drinking: at 720, 740 and 1140 days after transplantConclusion:• Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy
  17. 17. HEPATICENCEPHALOPATHY
  18. 18. • 299 patients with recurrent HE • (140 drug /159 placebo)• At least 2 previous episodes; in remission• Rifaximin 550 bid 6 mo• End point • Primary: time to 1st breakthrough HE • Secondary: time to 1st admission due to HE
  19. 19. Minimal Hepatic Encephalopathy• Not obvious cognitive deficits• Impaired quality of life• Difficult diagnosis, based on neuropsychometric and neuropsychological• Patients with MHE have little or no insight into their condition, especially their ability to drive
  20. 20. • Legal ramifications not yet evaluated• Reviewed all 50 states BMVs regulations and requirements for physicians to report potentially impaired drivers• Reviewed legal databases in search for lawsuits against physicians or patients related to HE
  21. 21. Driving and MHE• Few (6) states have regulations mandating physicians to report; 25 grant immunity for reporting• Minimal HE would not fit criteria for medical impairment for overt signs and symptoms are not present• No lawsuits were identified against physicians / patients related to HE• However…
  22. 22. Red journal suggests standardized evaluation
  23. 23. • 94 patients received either rifaximin 400 mg or placebo tid for 8 weeks• More patients receiving rifaximin achieved reversal of MHE (75.5% vs. 20% p<0.0001)
  24. 24. • Similar, 42 patients currently driving, received either rifaximin 550 mg or placebo bid, 8 weeks.• Percent reduction in total driving errors higher in treatment group (76% vs. 31%, p=0.013)
  25. 25. Rifaximin and MHE• Conclusions: • Rifaximin significantly improves both cognitive functions and HRQOL in patients with MHE. • Patients with MHE significantly improve driving simulator performance after treatment with rifaximin, compared with placebo
  26. 26. NASH
  27. 27. • TZDs and antioxidants can lead to improvements in NASH• Phase III, multicenter, double blind trial• 247 nondiabetic NASH • Pioglitazone (30 mg daily) • Vitamin E (800 IU daily) or • Placebo • 96 weeks
  28. 28. NAFLD – spectrum from benign steatosis tonecroinflamatory changes and fibrosis;Prevalence up to 39%Progressive disease in approximately 15%No definitive pharmacological treatment available
  29. 29. Atorvastatin plus vit E andC for Nash• 1,005 patients, both sexes, randomized to • Atorvastatin 20, vitamin C 1 g and vitamin E 1,000 IU vs. • Placebo, matching• CT scan Liver to spleen (LS) ratios were calculated on 455 patients at baseline and follow-up• Mean duration of follow-up was 3.6 years
  30. 30. Results• 80 patients had NAFLD at baseline• Baseline triglyceride (OR) = 1.003, P < 0.001) and BMI (OR = 0.10, P < 0.001) were independent predictors of NAFLD.• Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up, 70 vs. 34 % (OR = 0.29, P < 0.001).• 3 patients had increase in aminotransferases; after 2 years, levels improved in 2 of 3.
  31. 31. Conclusions• Atorvastatin plus vitamins C and E lowered the risk of moderate-to-severe hepatic steatosis by 70 % in a healthy population of 80 patients with NAFLD at baseline after 4 years of therapy.• Study limitations: • Difficult to determine which of the cocktail medications is/are active • Measurement of steatosis is not gold standard • Not evaluated in patients with significantly abnormal liver enzymes
  32. 32. VIRAL HEPATITIS
  33. 33. Conclusions• Response-guided telaprevir combination treatment for HCV infection – NEJM Sept 2011• Telaprevir alone or with Peg-Riba reduces HCV RNA in patients with geno 2 but not 3 – Gastro Jun 2011• Telaprevir for previously treated and untreated HCV infection. NEJM Mar 2011• Telaprevir for previously treated and untreated HCV infection. NEJM Jun 2011

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