1. Breakthrough Papers in
Hepatology in 2011
GI Hepatology Update 2012
Marco Lacerda

2. GENERAL HEPATOLOGY

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. High-dose UDCA and colon
cancer
• 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. High-dose UDCA and colon
cancer
• 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

7. High-dose UDCA and colon
cancer
• Conclusion
• Long term use of high-dose UDCA in
patients with PSC/UC is associated with
increased risk of colorectal neoplasia

8. • 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

9. 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%

10. 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

12. 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

13. • Steroids are treatment of choice for severe ETOH
hepatitis; however:
• 6 mo mortality approaches 65%

14. 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

16. 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

18. Early liver transplantation for
severe 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

19. Early liver transplantation for
severe 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

22. 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 transplant
Conclusion:
• Early liver transplantation can improve survival
in patients with a first episode of severe
alcoholic hepatitis not responding to medical
therapy

23. HEPATIC
ENCEPHALOPATHY

24. • 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

25. 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

26. • 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

27. 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…

28. Red journal suggests standardized evaluation

30. • 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)

31. • 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)

32. 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

33. NASH

34. • 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

35. NAFLD – spectrum from benign steatosis to
necroinflamatory changes and fibrosis;
Prevalence up to 39%
Progressive disease in approximately 15%
No definitive pharmacological treatment available

36. Atorvastatin plus vit E and
C 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

37. 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.

39. 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

40. VIRAL HEPATITIS

41. 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