A treatable form of alcoholic liver disease.
Alcoholic hepatitis is an inflammatory process based on the presence of steatosis, hepatocyte ballooning, he amorphous eosinophilic inclusions (Mallory bodies) and neutrophilic infiltration.
AH is a complex inflammatory state characterized by a high grade, systemic, inflammation, associated with liver tissue injury, portal hypertension, and extrahepatic organ dysfunction, especially acute kidney injury.
The liver is the main site to metabolize alcohol into acetaldehyde, which forms proteins, and DNA adducts that promote innate immune response, glutathione depletion, lipid, peroxidation, and mitochondrial damage.
Injured hepatocytes, release, high mobility group protein 1, which triggers inflammatory responses by activating the inflammasome-caspase-1 complex.
Alcohol related hepatitis is associated with immunosuppression with impaired monocyte in neutrophil phagocytic and oxidative burst capacity, rapid release of reactive oxygen species, and increased rates of infection.
Patients with AH have a higher rate of bacterial infection compared with those with decompensated, alcohol related cirrhosis, who do not have alcohol related hepatitis.
Elevated biomarkers of infection, such as serum, liposaccharide, bacterial DNA, and procalcitonin are associated with increased risk of multiorgan failure, and higher mortality in an AH suggesting infection contributes to increased rates of mortality.
Serum keratin-18 fragments correlate with histologic severity and 90 day mortality.
Excessive alcohol consumption increases gut permeability, and disrupts intestinal epithelial cell junctions and induces profound changes in the microbiome, including increased pathological bacteria.
The translocation of viable bacteria and microbial products to the liver, induces inflammation, hepatocyte death, and stimulates a fibrotic response.
Other inflammatory factors, such as chemokines, macrophage migratory inhibitory factor and complement contribute to hepatocellular injury.
The activation fibrogenic cell types that accumulate extracellular matrix around the hepatocytes and sinusoidal cells form a pattern favoring the development of portal hypertension.
Subsequently, there is failure in the hepatocyte regeneration and differentiation that results in the futile attempt to regenerate the liver.
There is a systemic inflammatory response syndrome and immune dysfunction that occurs, favoring bacterial infections, and the development of acute on chronic liver failure and multi organ failure.
A common complication of alcohol abuse.
Alcohol use disorder is a major cause of advanced liver disease and liver related hospitalization and death worldwide.
Alcohol is the cause of 50% of all deaths due to liver disease and alcohol associated liver disease will develop in approximately 35% of patients with alcohol use disorder.
Severity ranges from mild to severe liver inflammation, and can lead to jaundice, prolonged prothrombin time, and liver failure.
Alcoholic hepatitis is characterized by an abrupt onset of jaundice, malaise, decompensated liver disease, and coagulopathy.
At patients are jaundiced, often have ascites and edema, and some patients have severe caloric nutrition, and sarcopenia.
The presence of hepatic encephalopathy confers a poor prognosis.
Patient with tender and hepatomegaly have a poor prognosis.
Patients with signs of systemic infection with fever and neutrophilia should be evaluated for infection.
In its severe manifestation alcohol associated hepatitis is associated with bacterial infections and development of acute on chronic liver failure, multi organ failure, and a high short term mortality of 20 to 50% at three months.
Up to 40% of patients with severe disease die within 6 months after the onset of the clinical process.
A syndrome of jaundice and liver failure that occurs after decades of heavy alcohol use with a mean intake of approximately 100 gm per day.
Prevalence is not well known but its global incidence is probably increasing, especially among young adults in their 20s and 30s and women.
Its incidence has increased during the Covid-19 pandemic.
Typical age of presentation 40-60 years of age.
Patients may present several weeks after stopping alcohol abuse.
Because more men than women abuse alcohol, it is more common in men, but female sex is an independent risk factor.
Women are more susceptible to alcohol injury and cirrhosis, and young women constitute the fastest growing population assessed for liver transplantation in the US.
Type of alcohol used is does not affect the risk.
Prevalence of 20% in patients with alcoholism (Naveau).
Severe AH is life-threatening.
Cardinal sign is rapid onset of jaundice.
Clinical features include fever, hepatomegaly, jaundice, and anorexia.
May be associated with fever, ascites, proximal muscle loss, elevated alkaline phosphatase levels and hyperbilirubinemia..
Long-term alcohol consumption increases intestinal permeability, worsens endotoxemia, stimulates Kupffer cells activity and increases pro-inflammatory cytokines.
Associated with high levels of tumor necrosis factor-alpha , which activate apoptosis pathways and induce production of reactive oxygen species, especially superoxide anions, by liver mitochondria leading to cell death.
The above process is accompanied by mitochondrial depletion of glutathione, the primary antioxidant in cells.
Hepatocytes are increasingly sensitive to TNF-alpha, when antioxidant reserves are low.
May be associated with hepatic encephalopathy.
Clinically associated with enlarged and tender liver.
Hispanics are predisposed to the development of alcohol associated hepatitis, and genetic factors, such as variation in the gene in coding palatin-like phospholipase, domain containing protein, 3 (PNAPL, 3) influence disease severity, among persons with alcohol associated hepatitis.
Some factors, such as coffee, consumption and polymorphism in the hydroxy steroid 17, beta dehydrogenase, 13 have shown a protective role.
Laboratory evaluation reveals elevated aspartate aminotransferase more than twice normal, but rarely is higher than 300 IU per milliliter.
Serum alanine aminotranferase elevations are lower than that of aspartate aminotranferase and the ratio of the aspartate aminotranferase level to the alanine transferase is usually greater than 2.
High ratio of aspartate aminotranferase: alanine aminotranferase ratio possible related to reduced hepatic alanine aminotranferase activity , alcohol induced depletion of hepatic pyridoxal 5’phosphate and increased hepatic mitochondria aspartate.
White blood count elevation, neutrophil count elevation, serum bilirubin elevation, and elevated serum INR are present.
When associated with elevation of creatinine may portend the onset of the hepatorenal syndrome.
Associated with hepatocellular injury characterized by ballooned hepatocytes that often have amorphous eosinophilic inclusion bodies, Mallory bodies, surrounded by neutrophils.
Fat globules in hepatocytes, steatosis, is common finding in alcoholic hepatitis.
A characteristic lesion is intrasinusoidal fibrosis, which is fibrosis between the endothelial cell and the hepatocytes.
Features of alcoholic fibrosis of perivenular fibrosis, periportal fibrosis, and cirrhosis often coexist with findings of alcoholic hepatitis.
May have microscopic findings of foamy degeneration of hepatocytes and acute sclerosing hyaline necrosis.
Liver biopsy can provide prognostic information with histologic features of bridging, fibrosis or cirrhosis, hepatocellular canalicular or duct bilirubin stasis, neutrophil infiltration and megamitochondria that help predict 90 day mortality.
Diagnosis is usually made on clinical grounds with an application of history, physical exam, and laboratory findings: onset of jaundice within the previous eight weeks, ongoing consumption of more than three drinks a day for women and four drinks per day for men for six months or more, less than 60 days of abstinence between the onset of jaundice, the total serum bilirubin of more than 3 mg/dL, and AST level of more than 50 IU per liter, and the ratio of AST to ALT of more than 1.5, with both values less than 400 IU per liter, the ruling out of other liver diseases, such as drug induced, liver injury, and ischemic hepatitis.
Mortality from moderate alcohol associate hepatitis is 3 to 7% in the short to median term and 13 to 20% at one year, related to liver related complications in severe infections.
The mortality associated with an episode of alcohol associated hepatitis warranting hospitalization is approximately 20 to 50% at 90 days.
The main factor influencing long-term prognosis after an episode of alcohol associated hepatitis, is prolonged alcohol abstinence.
More than half the patients resume alcohol drinking after such an episode.
Even among patients who have undergone liver transplantation, alcohol relapse is frequent ranges from 15 to 50%
Treatment: includes alcohol abstinence, nutritional support and corticosteroids.
Goals for enteral nutrition for 35 to 40 kcal per kilogram of body weight per day with 1.5 g of protein content per kilogram per day.
Early detection, and treatment of infection may reduce associated mortality.
Bacterial and fungal infections are common in patients with severe alcohol associated hepatitis.
Up to 1/3 of patients with severe alcohol associated hepatitis, have acute kidney injury injury with the increase in 90 day mortality by a factor of nine.
The use of albumin and vasoconstrictors may be indicated for hepato-renal syndrome.
Renal replacement therapy could be initiated.
Corticosteroids are thought to reverse hepatic inflammation by decreasing circulating levels of pro-inflammatory cytokines including IL-8 and TNF.
Glucocorticoids have a transient beneficial effect in patients with severe alcohol associated hepatitis.
Pentoxifillin is thought to improve alcoholic hepatitis by protecting against the hepatorenal syndrome, possibly by modulation of TNF transcription.
The outcome of a four week treatment study with a combination of pentoxifylline and prednisolone did not improve six-month survival compared to prednisolone treatment alone (Mathurin P et al ), and the combination therapy is not recommended.
Approximately 40% of patients with alcohol hepatitis are responsive to corticosteroids.
Many patients have contraindications to the use of corticosteroids, such as acute infections.
Patients with alico alcoholic hepatitis are at increased risk for bacterial and fungal infections.
Patients whom develop infection while receiving corticosteroid therapy have higher rates of adverse outcomes, such as hepatorenal syndrome and worsening liver insufficiency.
Among patients with severe alcohol related hepatitis receiving steroids, antibiotics, such as amoxicillin and clavulanate, do not improve survival at 60 days compared with placebo.
Pentoxifylline reduces short term mortality in acute hepatitis.
liver transplantation is indicated in patients with severe forms of alcohol associated hepatitis who do not have a response to medical therapy.