5 lacerda liver disease

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

GENERAL HEPATOLOGY

• 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

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

• 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

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

High-dose UDCA and colon cancer

• 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

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%

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

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

• Steroids are treatment of choice for severe ETOH hepatitis; however:

• 6 mo mortality approaches 65%

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

• Conclusion:• Improved one month survival and

development of HRS however; • No improvement in primary outcome –

overall survival at 6 months

Steroids plus NAC in severe ETOH hepatitis

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

• 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

Early liver transplantation for severe alcoholic hepatitis

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

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

Conclusion:

HEPATIC ENCEPHALOPATHY

• 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

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

• 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

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…

Red journal suggests standardized evaluation

• 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)

• 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)

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

NASH

• 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

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

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

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.

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

VIRAL HEPATITIS

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