Management of Alcoholic Liver Disease. Hafez Fakheri Professor of medicine, Sari, Iran

Transcription

1 Management of Alcoholic Liver Disease Hafez Fakheri Professor of medicine, Sari, Iran

2 Alcoholic Hepatitis

3 Scores DF = (4.6 x [ PT- control PT]) + (bili ) MELD = 10 * ((0.957 * ln(cr)) + (0.378 * ln(bil)) + (1.12 * ln(inr))) GAHS: Age, WBC, Urea, Bili, INR

4 28 days mortality 7% 25-45% (32%) 13% 54% 4% 55%

5 Causes of death for AH First 84 days: Liver Failure HRS Infection Dan Med J, 2013, 1951 AH death,

6 General management in AH Alcohol abstinence Prevention and treatment of alcohol withdrawal Fluid management Nutritional support Infection surveillance Prophylaxis against gastric mucosal bleeding Discontinuing nonselective beta blockers in patients with severe AH

7 Alcohol abstinence All patients ( mild - moderate / sever AH) Baclofen may aid Risk for alcohol withdrawal Combined approaches (cognitive behavioral therapy, motivational enhancement therapy, medical care) reduce recidivism

8

9 Hydration All patients ( mild - moderate / sever AH) Poor oral intake prior to presentation Volume expansion, to prevent renal failure Overhydration should be avoided, particularly in stigmata of cirrhosis, since it increase ascites, lower the Na, precipitate GIB from varices

10 Patients with AH often develop ARF which negatively impacts survival Most frequent causes of ARF are Type 1 HRS and tubular necrosis Severe AH is a risk factor of radiocontrastinduced nephropathy

11 Nutritional Support All patients ( mild - moderate / sever AH) Most are malnourished Signs of tissue wasting and severe protein-calorie malnutrition (low albumin, edema) in almost Indices of malnutrition correlated with the severity of liver disease Improvement in liver function and histology,but not consistently found reductions in mortality

12 Patients eat almost no calories unless spoon-fed by relatives. If the patient is not taking enough calori, a duodenal feeding tube can improve intake Enteral feeding is preferred over IV nutrition Protein feeding is well tolerated Protein should not be routinely restricted In encephalopathy associated with protein feeding, use of branched-chain amino acids may be helpful

13 Adequate calories and protein, vitamin ( B1, folate, B6) and mineral ( p, mg) Consider risk of Wernicke s encephalopathy, supplement with B-complex Daily protein( 1.5 g/kg ) independent from encephalopathy Compensate liposoluble vitamins deficiency

14 Infection surveillance Infection screening ; ¼ in admited patients Impossible to distinguish between the fever of hepatitis and infection Blood and urine cultures in evidence of infection Sputum cultures in productive cough CSF examined and cultured in fever and neurologic signs of CNS infection rather than encephalopathy Ascitic fluid culture, cell count, protein, albumin Clinical or biological deterioration disclose a higher risk of infection and should be screened repeatedly

15 Acid suppression Prophylaxis against gastric mucosal bleeding with a PPI, H2-blocker, or Sucralfate particularly if the patient is in an ICU, GC, OB+

16 Discontinue nonselective beta blockers If indicated, should not be started until after AH have recovered Due to the 90 % acute kidney injury with beta blocker in this setting, NOT perform screen endoscopy for varices until the patient has recovered (outpatient) If large varices are detected, beta blockers are started by physicians who are not familiar with the intolerance to these agents

17 Specific therapy in severe AH 1-Corticosteroids %85 %65 28

18 Severe AH (DF 32) *****GC is not recommended in Non sever AH General supportive care Prednisolone has traditionally been used Prednisolone is preferred over prednisone Start with 40 mg

19 Treatment is continued for 28 days For those who receive 28 days of prednisolone, finish therapy with a 16-day taper (decrease the dose by 10 mg/day every 4 days until a dose of 10 mg/day is reached, at which point decrease it by 5 mg/day every 3 days)

20 Exclusion criteria for GC 1. Concomitant pancreatitis 2. GIB 3. Renal failure( HRS) 4. Active infection *GC may not be precluded in patients with infection after appropriate antibiotic therapy

21 Infection developed in 24% of patients who received GC More likely to develop in null responder to GC (43% vs 11 %)

22 After 7 days on GC, Lille score >0.45 predicts poor response 40 % of patients had a Lille score >0.45 High 6 mns mortality in lille score >0.45 (75% vs 15%) Interrupt GC In poor responders Lille score = [ * (age in yrs) * (albumin day 0 in g/l) * (evolution in bili in mm) * (renal insufficiency) * (bili day 0 in mm) * (PT in seconds)].

23 Specific therapy in severe AH 2-PTX and antioxidant 400 mg tds (400 mg/day in cr clearance <30 ml/min)x 28 days

24

25 Several studies failed to show a benefit with regard to mortality, while other studies suggested that PTX may prevent HRS and/or decrease mortality The largest meta-analysis supports that PTX decreases the risk of acute kidney injury and suggests that PTX improves mortality compared with placebo, but is not superior to glucocorticoids

26 Role of PTX in AH remains uncertain Alternative in: *patients at risk for sepsis *becoming lost to follow-up after discharge (not be tapered off,serious SE) Do not treat with PTX (lack of efficacy data ) However, AASLDand the EASL, do recommend PTX in who cannot receive GC

27 In poor responders to GC PTX does not effective Switch to PTX or MARS (molecular adsorbent recirculating system) appears not to modify the outcome

28 Possibly effective treatments Entral feeding: deserves to be tested in combination with corticosteroids PN + N-AC( antioxidant) have synergistic effects & recommend by EASL Granulocyte colony-stimulating factor: Mobilize bone marrow-derived stem cells and promote hepatic regeneration

29 Ineffective treatments Anti-TNF agents PTU Colchicine

30 Liver transplantation in AH

31 6-mo rule : 85% of transplant programs require Patients who do not respond to steroids have a the 3-mo mortality about 70% and in (HRS) >90% Substance abuse training before & after transplant(alcohol Addiction Unit (Alcohology unit) within transplant center : relapse rate 24-29% good family support and living donor

32 Long-term management of ALD

33 Abstinence from Alcohol Alcoholic fatty liver: steatosis resolution(6wks) Fibrosis/Cirrhosis: improve fibrosis, ascites portal pressure in some Low decompensation Higher survival rates at 1, 5, 10 yrs (95% vs 63%, 61 vs 36%, and 31 vs 11 %)

34 Medications to treat alcohol dependence Only 10% maintain safe drinking after 1 year and 75% relapse Referred for treatment for alcohol abuse or dependence Disulfirum is the oldest, but has poor tolerability and there is little evidence that it increases abstinence Short-term treatment with opioid antagonists such as naltrexone (available in injectable extended release form) is useful in lowering the risk of relapse The GABA B receptor agonist improve abstinence and decrease relapse. Baclofen is a relatively safe and effective agent (devoid of hepatotoxicity) in advanced cirrhosis, and is the most preferred mode of treatment

35 N-methyl-D-aspartate receptor blockers are being investigated as a new pharmacological treatment Alcohol abstinence support groups may also be helpful for alcohol cessation Majority of patients classed as alcoholics also smoke. Smoking cessation decreases progression of hepatic fibrosis, risk of sepsis related deaths, risk of HCC, and post-transplant complication

36 Nutritional therapy Severe malnutrition in CP Class A: 45%, C:95% Malnutrition associate high 1-year mortality (20% vs 0%) and complication(65% vs 13%) Alcoholism is associated with nutritional deficiencies; protein calorie malnutrition, deficiencies of vitamins and trace minerals Protein calorie malnutrition increases the risk of complications; infection, encephalopathy, ascites

37 Nutritional therapy is indicated for alcoholic fatty liver who are malnourished Nutritional therapy is indicated for Alcoholic cirrhosis (protein, carbohydrate, lipid metabolism all affected) Eat multiple times per day, including breakfast and a nighttime snack. The diet should consist of higher amounts of protein (1.2 to 1.5 g/kg) and total calories (35 to 40 kcal/kg) in a standard healthy diet Treat any vitamin or mineral deficiencies

38 Nutritional therapy has not been shown to improve mortality but improves nitrogen balance and albumin levels, decreases hospitalization rates, and decreases the frequency of complications related to cirrhosis (encephalopathy, GIB, ascites)

39 Depletion of hepatic glycogen stores in cirrhotic patients leads to early starvation at 12 hrs (leads to peripheral muscle proteolysis), compared with 48 hrs in normal individuals Therefore, protein restriction should be limited to an initial hrs in hepatic encephalopathy Branched-chain amino acids may be substituted for standard enteral formula if the latter causes hepatic encephalopathy

40 Experimental Therapies None of the existing therapies (silymarin, SAMe, vitamin E, and PTX, colchicine) improved survival in alcoholic cirrhosis other than abstinence Metadoxine,antioxidant,approved for the treatment of ALD in Europe that may be effective

41 Complications of cirrhosis Patients with decompensated cirrhosis are managed the same as patients with other forms of end-stage liver disease and require treatment for complications such as ascites, variceal bleeding, and encephalopathy. In some cases, liver transplantation may be required

42 Liver Transplantation 1 yr mortality: 30% in alcoholic cirrhosis with ascites, 50% in ascites + variceal bleeding, 65% in encephalopathy CP score >11 in spite of at least 6 mns of abstinence have improved survival with liver transplantation In CH- B cirrhosis mortality increases with transplant (different malignancies)

43 HCC In alcoholic liver disease, the chance of HCC is 2 to 3-times higher and co-existent (HCV) doubles the risk Higher in males and the elderly

44 AASLD 2010

45

46

47

48

49 Five-year survival in alcoholic cirrhosis can be best predicted by Child Pugh (CP) score patients with cirrhosis can be stratified into groups A: 5 6; B: 7 8; or C: 9) One-year mortality in CP score A, B, and C are 15%, 25 30%, and 70 80%

50 A recent, large randomized controlled trial of 270 patients with Bx documented severe AH testing the combination of(pn + PTX) failed to show any benefit over GC alone

51

52

53 Steroids or PTX for Alcoholic Hepatitis (STOPHA) 1,103 patients with a clinical diagnosis of severe AH studied into 4 arms: A. Placebo/Placebo; B. PN/ Placebo C. PTX/Placebo; D. PTX/PN At 28 days, death were 17%, 14%, 19%, and 13%. PN reduced the risk of 28-day mortality, but was not sustained at 3 mns and 1 yr Concluded PTX has no impact on disease progression and should no longer be used for treatment of severe AH

54