Alcoholic hepatitis

Alcoholic hepatitis by Dr shoaib Arshad internal medicine

1. By Dr Shoaib Arshad Alcoholic Hepatitis

2. Objectives INTRODUCTION CLINICAL MANIFESTATIONS INVESTIGATIONS AND DIAGNOSIS ASSESSING DISEASE SEVERITY DIFFERENTIAL DIAGNOSIS MANAGEMENT AND PROGNOSIS

3. INTRODUCTION Excessive alcohol consumption is associated with a range of hepatic manifestations, including A lcoholic fatty liver disease (with or without steatohepatitis), A lcoholic hepatitis , and C irrhosis .

4. What is the amount of alcohol intake that puts an individual at risk for alcoholic hepatitis?

5. Alcoholic hepatitis typically occurs after more than 10 years of regular heavy alcohol use; average consumption in one study was 100 g/day (the equivalent of 10 drinks per day)

6. Is alcohol intake related to Gender?

7. Laboratory tests Moderate elevations of the AST and ALT (typically less than 300 int. unit/L, rarely higher than 500 int. unit/L) An AST:ALT ratio ≥2 An elevated serum bilirubin An elevated gamma-glutamyl transferase ( GGT ) A leukocytosis with a predominance of neutrophils An elevated international normalized ratio ( INR ) In addition, patients may have low serum albumin and prealbumin levels due to malnutrition and decreased synthesis 

8. Hematologic abnormalities Common in moderate to severe alcoholic hepatitis. Moderate leukocytosis (<20,000/ microL ) is a frequent finding Macrocytosis suggests longstanding disease and may reflect poor nutritional status, cobalamin or folate deficiency, toxicity of alcohol, and/or increased lipid deposition on red cell membranes T hrombocytopenia can result from primary bone marrow hypoplasia (which can be due to alcohol and is usually brief) and/or splenic sequestration due to portal hypertension and an enlarged spleen (" hypersplenism ")

9. Imaging tests Abdominal imaging (ultrasound, computed tomographic scan, magnetic resonance imaging) fatty change in the liver , evidence of underlying cirrhosis , or ascites . Transabdominal ultrasound may also reveal parallel tubular structures in the liver, thought to represent the dilated hepatic artery adjacent to a portal vein radical.   Doppler flow studies of the hepatic artery may reveal an elevated peak systolic velocity or an increase in vessel diameter. Transient elastography may be useful in determining the likelihood of cirrhosis .

10. DIAGNOSIS The diagnosis is mainly CLINICAL. Clinical and laboratory features and heavy alcohol use (typically >100g per day for more than 20 years) patient presents with jaundice ,+/- Ascites, moderately elevated aminotransferases (typically < 300 int. unit/mL and rarely higher than 500 int. unit/mL), an AST:ALT ratio ≥2 , an elevated serum bilirubin (>5 mg/dL or 86 micromol /L), and an elevated INR . R ule out other common causes of acute hepatitis ● Anti-hepatitis A IgM ● Hepatitis B surface antigen, anti-hepatitis B core IgM ● Anti-hepatitis C virus (HCV) antibodies, hepatitis C RNA ● Biliary obstruction / Budd-Chiari syndrome using ultrasound with Doppler

11. Is liver biopsy always needed? Although alcoholic hepatitis can be suspected on the basis of clinical and biochemical clues, liver biopsy remains the gold standard diagnostic tool. It confirms the clinical diagnosis of alcoholic hepatitis in about 85% of all patients and in up to 95% when significant hyperbilirubinemia is present. However, whether a particular patient needs a biopsy is not always clear. The American Association for the Study of Liver Diseases ( AASLD ) recommends biopsy in patients who have a clinical diagnosis of severe alcoholic hepatitis for whom medical treatment is being considered and in those with an uncertain underlying diagnosis . In addition to confirming the diagnosis and staging the disease, liver biopsy has prognostic value .

12. Assessing disease severity   The Maddrey discriminant function ( MDF ) and the Model for End-stage Liver Disease ( MELD ) score are the most commonly used to help identify patients who are more likely to benefit from pharmacologic therapy. Other validated scores include the Glasgow alcoholic hepatitis score , the ABIC score (which includes age, serum bilirubin, international normalized ratio, and serum creatinine), and the Lille score (which is used to determine if a patient is responding to treatment)

13. MANAGEMENT Treatment considerations for all patients  — Consultation with a gastroenterologist is recommended Alcohol abstinence is the cornerstone of treatment of alcoholic hepatitis. treatment of withdrawal. Hydration( use albumin rather than crystalloid for patients with prerenal azotemia and underlying cirrhosis). Treat complications such as infections or conditions related to complications of cirrhosis and portal hypertension such as hepatic encephalopathy , ascites , or variceal bleeding .  Renal failure and acute kidney injury Ulcer prophylaxis Discontinue nonselective beta blockers  — In patients with severe alcoholic hepatitis, the use of nonselective beta blockers has been associated with an increased risk of acute kidney injury (AKI). Screen for infection . Patients with alcoholic hepatitis should be screened for infection, as about 25% of those with severe alcoholic hepatitis have an infection at admission. Vitamin E , silymarin , propylthiouracil , colchicine , and oxandrolone (anabolic steroid) have also been studied, but with no convincing benefit. Nutrition  

14. Nutrition  —  Most patients with severe alcoholic hepatitis are malnourished and require nutritional support. The goal of nutritional support is to provide adequate calories and protein , in addition to vitamin ( eg ,  thiamine , folate , and pyridoxine ) and mineral ( eg , phosphate, magnesium ) repletion.  vitamin K  is usually given to patients with a prolonged prothrombin time , even though this regimen is often ineffective because the coagulopathy is reflection of underlying liver failure than vitamin K deficiency . Oral vitamin K is not well absorbed; a parenteral route of administration is preferred for these patients. Protein intake is well tolerated and should not be restricted in patients with alcoholic hepatitis. In patients who develop encephalopathy associated with protein feeding, the use of branched-chain amino acids may be helpful.

15. Mild to moderate alcoholic hepatitis :  Abstinence from alcohol is the mainstay of treatment in patients with mild to moderate alcoholic hepatitis ( Maddrey discriminant function [MDF] <32) ( calculator 1 ). general supportive care ( eg , nutritional support and hydration ) treatment with glucocorticoids is not recommended in patients with mild to moderate alcoholic hepatitis . While glucocorticoids may provide a short-term survival benefit in alcoholic hepatitis, patients with mild to moderate disease have a relatively favorable prognosis, and therefore, potential benefits do not outweigh potential harm.

16. Severe alcoholic hepatitis Glucocorticoids Indications and contraindications  — In addition to general supportive care, we suggest treatment with glucocorticoids (40 mg per day) for patients with severe alcoholic hepatitis (DF ≥32 ( calculator 1 )). provided there are no contraindications to its use ( eg , active bacterial or fungal infection or chronic hepatitis C virus or hepatitis B virus infection ) Prednisolone is preferred over  prednisone  because the latter requires conversion to prednisolone (the active form) in the liver, a process that may be impaired in alcoholic hepatitis.  Methylprednisolone  32 mg daily by intravenous route is used for patients who cannot take ora l.

17. For patients who respond to treatment , we continue  prednisolone  for 28 days, and finish therapy with a 16-day prednisolone taper (we decrease the dose by 10 mg per day every four days until a dose of 10 mg per day is reached , at which point we decrease it by 5 mg per day every three days ). Response and early termination of treatment  — For patients who receive glucocorticoids, the duration of treatment is 28 days . However, we stop therapy if fail to show signs of improvement after one week ( ie , those who fail to have improvement in their bilirubin or MDF ) ( calculator 1 ). The Lille score is another method to determine if patients with alcoholic hepatitis are responding to glucocorticoid therapy.

18. Pentoxifylline    Pentoxifylline  is an alternative to glucocorticoids for patients who have contraindications to glucocorticoids or who are at risk for sepsis or for failing to follow up after discharge. some authorities favor pentoxifylline because it may provide more benefit for certain subgroups of patients (those with renal failure ) compared with glucocorticoids. Pentoxifylline  is given as 400 mg three times per day (400 mg once per day in patients with a creatinine clearance <30 mL per minute). A bilirubin less than 5 mg/dL may be an appropriate time to stop therapy. Pentoxifylline should be stopped earlier in patients who develop dyspepsia that limits oral intake. Pentoxifylline inhibits tumor necrosis factor (TNF) synthesis, which is increased in patients with alcoholic hepatitis.

19. Liver transplantation   — Patients with severe alcoholic hepatitis who fail to respond to treatment with glucocorticoids or  pentoxifylline  may require liver transplantation. Liver transplantation for alcoholic liver disease has been a topic of great medical and social controversy. Many countries require 6 months of abstinence from alcohol before placing a patient on the liver transplant list, posing a major obstacle to patients with alcoholic hepatitis, as almost all are active drinkers at the time of presentation and many will die within 6 months . Refractory patients  — Patients with severe alcoholic hepatitis who do not respond to supportive care, nutritional therapy, and pharmacologic therapy, who are not candidates for liver transplantation, and who have multiple ( ≥four ) organ failures, may be considered for palliative therapy

20. PROGNOSIS Mortality  — Mortality rates among patients who do not receive pharmacologic therapy ( eg ,  prednisolone ) for alcoholic hepatitis are variable. In patients with severe alcoholic hepatitis (typically defined by a Maddrey discriminant function ≥32 ( calculator 1 )), short-term mortality rates are high (approximately 25 to 45 % at one month ) patients with mild to moderate alcoholic hepatitis have lower short-term mortality rates (<10 percent at one to three months ) In one study, the primary causes of death were hepatic failure (55 percent), gastrointestinal bleeding (21 percent), and sepsis (7 percent)

21. ■ REFERENCES CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 82 • NUMBER 4 The American Journal of Medicine - "The Green Journal"  © 2021 UpToDate.