• Alcoholic hepatitis is a clinical syndrome developing as a result of excessive and usually lengthy alcohol consumption and characterized by acute jaundice and liver failure.
• Severe alcoholic hepatitis requires hospital treatment, and the short-term mortality is high.
• The most important tasks in emergency services are differential diagnosis and the detection of any infection.
• In addition to symptomatic treatment, glucocorticoids may be needed.
• It is important to distinguish between alcoholic hepatitis and other acutely decompensated liver cirrhosis that must not be treated with glucocorticoids.
• Patients with suspected alcoholic hepatitis should be referred to specialized care as an emergency.

• Most patients are 40–60 years old, 60% of them male.
• Excessive alcohol consumption (more than 6–10 servings [one serving = about 12 g of pure alcohol] per day for a few weeks) almost invariably causes fatty liver.
• If excessive alcohol consumption continues, about 20% of patients develop steatohepatitis and some of them clinical alcoholic hepatitis.
  • The risk of disease depends on factors such as the level of alcohol consumption, drinking habits, age, sex, genetic factors, obesity, diabetes, smoking and intestinal microbiota.
• Even though alcoholic hepatitis has an acute onset, there is nearly always an underlying chronic liver disease. Nearly all patients have at least moderately severe fibrosis, and 80% have cirrhosis.

• Jaundice (icterus)
• Nausea
• Pain in the upper right abdominal quadrant
• Leukocytosis
• Fever in half of patients
• Enlarged liver tender to palpation in some patients
• Ascites and encephalopathy as symptoms of liver failure in some patients

• Basic blood count with platelet count, CRP, ALT, AST, ALP, bilirubin, albumin, prothrombin time or INR, Na, K, creatinine, glucose, amylase, and blood PEth as necessary (levels may be low if some time has passed since stopping alcohol consumption)
• Abdominal ultrasonography or computed tomography
• Differential diagnostic investigations as considered necessary: HAVAb, HCVAb, HBsAg, HEVAb, antinuclear antibodies, smooth muscle antibodies, IgG, (nucleic acid detection of CMV and EBV)
• Exclusion of infection: chest x-ray, urine sample, blood culture, ascites sample (to exclude spontaneous bacterial peritonitis)

• If the following 4 criteria are met, the probability of alcoholic hepatitis is according to a study more than 90% ⁸ .
  1. Alcohol consumption: average daily ethanol consumption exceeding 40 g (3–4 servings) or 50 g (4–5 servings) in women and men, respectively, over a minimum of 6 months.
     • In most patients, the daily consumption has exceeded 150–200 g ethanol (12–20 servings) for 5 years.
  2. Acute jaundice: bilirubin levels exceed 50 μmol/l and no more than 2 months have passed since stopping alcohol consumption.
  3. AST of 50–500 U/l; ALT may be within the reference range.
  4. AST/ALT ratio > 1.5, in less than 2% of patients < 1.5.
• If additionally the Model for End-stage Liver Disease (MELD) score https://www.mayoclinic.org/medical-professionals/transplant-medicine/calcu... exceeds 25, the diagnosis of alcoholic hepatitis is almost certain.
• In unclear cases, liver biopsy helps with diagnosis.
  • Biopsy typically shows steatohepatitis, ballooning of hepatocytes, pericellular and sinusoidal fibrosis, neutrophil infiltration and Mallory–Denk bodies.
  • Histological changes may remain for several months after alcohol consumption is stopped.

Differential diagnosis

• Bile duct obstruction, malignancy, abscess: abdominal imaging, in hospital usually by computed tomography
• Other decompensated liver cirrhosis (Cirrhosis of the liver)
• Autoimmune hepatitis (Autoimmune hepatitis) or viral hepatitis (Viral hepatitis) (keep hepatitis E in mind)
• Drug-induced liver injury (DILI): patient history

• Treatment depends on the severity of the disease, which according to current recommendations should be defined by MELD scoring https://www.mayoclinic.org/medical-professionals/transplant-medicine/calcu.... MELD scoring has been found to be better able to distinguish between various disorders than the previously favoured Maddrey index.
  • A MELD score > 20 suggests severe alcoholic hepatitis requiring hospital treatment.

Symptomatic treatment

• MELD ≤ 20: initial treatment of mild alcoholic hepatitis is symptomatic.
  • Active screening and effective treatment of infections
  • Treatment of fluid and electrolyte balance
  • Correction of nutritional status (see below)
  • Thiamine 250 mg i.m. or i.v. for 3–5 days, then 50–100 mg/day p.o. and pyridoxin (vitamin B6) 50–100 mg/day p.o.
  • Treatment of alcohol withdrawal symptoms
  • Treatment of complications of cirrhosis (such as ascites and encephalopathy)

Glucocorticoid treatment

• MELD > 20: initial treatment of severe alcoholic hepatitis involves consideration of glucocorticoid treatment in addition to symptomatic treatment.
• Contraindications to glucocorticoid treatment
  • Intestinal bleeding
    • Treatment should be considered only after intestinal bleeding has been treated and followed up for 2 days without recurrence
  • Severe infection
    • Treatment can be started when the infection is healing
  • Active hepatitis B or tuberculosis
  • Multiple organ failure or acute pancreatitis
  • Severe acute kidney injury
  • MELD score > 50
• Prednisolone 40 mg once daily p.o.
  • Improves the predicted 1-month survival in severe alcoholic hepatitis but not the 3-month or 1-year survival.
  • Patients with a MELD score of 25–39 benefit most from a glucocorticoid.
  • Patients whose bilirubin levels decrease spontaneously and consistently by at least 20% from baseline within the first few days do not appear to benefit significantly from glucocorticoids.
  • After one week of glucocorticoid treatment, the response should be assessed by calculating the Lille score http://www.lillemodel.com/lilleINR.asp.
    • A Lille score of < 0.45 means good response to glucocorticoids. In this case, prednisolone can be given for a further 3 weeks, after which the dose should be reduced by 5 mg every 1–2 weeks, for example.
    • Lille scores of 0.45–0.56 signify no clear response. If there are no alternative treatments available, prednisolone can be continued under careful monitoring but it should be withdrawn if liver function continues to deteriorate. Bilirubin concentration is the most important single measure of response.
    • If the Lille score is > 0.56, withdrawal of glucocorticoids is recommended because continuing the treatment would worsen the prognosis and increase the risk of infections. In this case, palliative treatment should be started.

Infections

• Twenty-five percent of hospitalized patients have a bacterial infection at admission and a further 25–30% develop such an infection during follow-up. Fungal and viral infections are also possible.
• Antimicrobial prophylaxis does not improve the 3-month survival ¹ even though it reduces infections.
• Development of an infection during glucocorticoid treatment is a sign of poor prognosis, and pausing or withdrawing the treatment should be considered.

Diet therapy

• The nutritional state of most patients is affected because many of the calories have been obtained from alcohol. Correction of nutrition is therefore one of the cornerstones of the treatment of alcoholic hepatitis.
• The total energy requirement is 30–40 kcal/kg/day and the protein requirement 1–1.5 g/kg/day.
• The risk of refeeding syndrome (see e.g. https://www.rightdecisions.scot.nhs.uk/tam-treatments-and-medicines-nhs-hi... https://www.ncbi.nlm.nih.gov/books/NBK564513/) must be kept in mind. The syndrome can be prevented by active correction of electrolyte imbalances, careful beginning of nutrition and paying attention to hypophosphataemia in particular.
• Fasting and long pauses between meals should be avoided due to strong catabolism. Frequent snacks and additional nutrition given in the evening are recommended.
• Good control of blood glucose should be ensured to utilize nutrients effectively and to prevent catabolism due to hyperglycaemia.

• As soon as signs of recovery are seen in a patient with alcoholic hepatitis, appropriate treatment of intoxicant abuse and rehabilitation should be arranged, and its seamless continuation in outpatient care should be ensured before the patient is discharged.
• After alcoholic hepatitis, the patient should exercise total abstinence because even minor alcohol consumption has been found to affect the prognosis.
• Follow-up should be continued on an outpatient basis at 1, 3 and 6 months after discharge, for example, until liver values have normalized and the symptoms (ascites, encephalopathy) have been eliminated.
• Follow-up examinations: basic blood count with platelet count, ALT, AST, bilirubin, prothrombin time or INR, albumin, creatinine, Na and K and, to ensure abstinence and to assess the need for treatment of intoxicant abuse, PEth as necessary
• At 3–6 months, liver elastography or the Enhanced Liver Fibrosis (ELF) test should be performed to examine whether there is liver cirrhosis, unless the patient is already known to have cirrhosis.
• Patients suspected of having liver cirrhosis (result of elastography > 12 kPa, ELF > 11.3) should be referred for further investigations and follow-up for cirrhosis (Cirrhosis of the liver).

• In mild alcoholic hepatitis, the 3-month mortality is less than 10%.
• In severe alcoholic hepatitis, the 3-month mortality is about 30%. If the Lille score http://www.lillemodel.com/lilleINR.asp is > 0.45, the 6-month mortality is 75%.
• A large liver detected in imaging has a higher recovery potential than a small cirrhotic liver.
• A significant proportion of patients have other organ failure in addition to liver failure, associated with a higher risk of infections, poorer prognosis and lower probability of response to glucocorticoids. However, if a response meeting the Lille criteria is achieved, the benefit for survival from glucocorticoids prevails regardless of other organ failure.
• After initial alcoholic hepatitis, further prognosis (> 3–6 months from falling ill) depends on whether alcohol consumption is stopped or continued.
  • Five years after recovery from alcoholic hepatitis, mortality is 26% in those who remained abstinent and 59% in those who continued drinking alcohol.
  • Starting rehabilitation for intoxicant abuse within one month of discharge from hospital is associated with a decreased risk of rehospitalization (risk ratio 0.2), lower risk of relapse (risk ratio 0.1) and reduced mortality (risk ratio 0.2).