HAV-picoRNA virus, pt can not go to work until non-effective HBV-DNA HCV- HDV-directly cytotoxic to hepatocytes, other secondary damage Must have >2.5 billi to see jaundice ETOH Liver Disease- OCPs cause bleeds in the liver NSAIDs cause renal failure LIver fx pathway
asterixis, fetor hepaticus, spider angioma, testicular atrophy, gynecomastia Stage I-apathy, anxiety, decreased attention, mild flap, speech disruption II-lethargy, flap, disorientation, loss of sphincter control III-stupor c hyperreflexia, Babinski’s IV-coma Etiology · Renal failure: Renal failure leads to decreased clearance of urea, ammonia, and other nitrogenous compounds. · Gastrointestinal bleeding: The presence of blood in the upper gastrointestinal tract results in increased ammonia and nitrogen absorption from the gut. Bleeding may predispose to kidney hypoperfusion and impaired renal function. Blood transfusions may result in mild hemolysis, with resulting elevated blood ammonia levels. · Infection: Infection may predispose to impaired renal function and to increased tissue catabolism, both of which increase blood ammonia levels. · Constipation: Constipation increases intestinal production and absorption of ammonia. · Medications: Drugs that act upon the central nervous system, such as opiates, benzodiazepines, antidepressants, and antipsychotic agents, may worsen hepatic encephalopathy. · Diuretic therapy: Decreased serum potassium levels and alkalosis may facilitate the conversion of NH4+ to NH3. · Dietary protein overload: This is an infrequent cause of hepatic encephalopathy Lactulose (traps ammonia by acidifying the feces) 30 cc PO or PR (300 mL lactulose plus 700 mL water, given as a retention enema every 4 hours as needed) Lactulose may be effective, but less so than abx (Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004) Go-lytely also has very good effects Flumazenil 2 mg IVP for severe encephalopathy, should have response in 6 hrs or it has poor prognostic associations ACP Journal Club 2003, Jan-Feb 138:15. (Ailment Pharm Ther. 2002; 16:361-72) Meta-analysis of flumazenil vs. placebo showed clinical and EEG improvement. Neomycin 250 mg QID protein restriction Ammonia levels do not correlate c severity (very sensitive (90%), not specific) Fulminant Hepatic Failure (FHF) Encephalopathy in this setting is actually caused by increased permeability of the blood brain barrier with resultant brain edema. Brain edema can be detected using transcranial doppler ultrasound. It looks at mean flow velocity in the middle cerebral artery. May need mannitol, CVVH, pentobarb coma, hypothermia. Rifaxmin is probably the most effective treatment (N Engl J Med 2010; 362:1071-1081) PEG was more effective than lactulose (JAMA Intern Med. 2014;174(11):1727-1733.) give 4 L of PEG administered orally or via nasogastric tube, again at the discretion of the treating physician. PEG was administered in a single dose over 4 hours
Transaminase levels > 5000 U/L
Only 3 categories of hepatic insult commonly produce a transaminase level > 5000 U/L: (1) a toxic event, such as acetaminophen toxicity; (2) ischemic hepatopathy; and (3) infection by atypical viruses such as HSV (Mayo Clin Proc, Vol. 81, pg. 1097).
<a name=”myth–interpretation_of_a_single” id=”%3Cstrong%3Emyth%26%238211%3Binterpretation_of_a_single” class=”sectionindex”>
Myth–Interpretation of a single ammonia level in patients with chronic liver disease can confirm or rule out hepatic encephalopathy
Can J Emerg Med 2006;8(6):433-5 The degree of the correlation between ammonia levels and the severity of HE continues to be controversial. What is evident from the literature is that a single normal ammonia level does not rule out HE in a patient with CLD, and serial levels may not correlate with the evolving clinical picture. An ammonia level is merely a data point among the constellation of variables that may contribute to the development of HE and, for now, the final diagnosis remains a clinical one. Reliance on ammonia levels to make the diagnosis of HE is inappropriate and perhaps dangerous if it results in failure to seek other causes of altered mentation in ED patients with CLD. Failure of liver within 8 weeks of development of disease
>250 PMNS=SBP subtract 1 pmn for every 250 red cells in a traumatic tap E. Coli, Klebsiella, Strep. >250 WBCs or a difference of .1 between ABG and Ascites pH (or <7.34) RX c Amp and Gent Hepatic Abcess-pyogenic or amebic We studied the use of reagent strips for diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. A reagent strip for leukocyte esterase designed for the testing of urine with a colorimetric 5-grade scale (0 to 4) was used to evaluate ascitic fluid in 228 nonselected paracentesis performed in 128 cirrhotic patients. We diagnosed 52 SBP and 5 secondary bacterial peritonitis by means of polymorphonuclear cell count and classical criteria. When we considered positive a reagent strip result of 3 or 4, sensitivity was 89% (51 of 57), specificity was 99% (170 of 171), and positive predictive
value was 98%. When we considered positive a reagent strip result of 2 or more, sensitivity was 96% (55 of 57), specificity was 89% (152 of 171), and negative predictive value was 99%. In conclusion, the use of reagent strips is a rapid, easy to use, and inexpensive tool for diagnosis of ascitic fluid infection. A positive result should be an indication for empirical antibiotic therapy, and a negative result may be useful as a screening test to exclude SBP. (HEPATOLOGY 2003;37:893-896.) Precipitants of Acute Decompensation in Chronic Liver Disease
- Variceal or GI Bleeding
- Alcoholic Hepatitis
- APAP overdosing
- Autoimmune hepatitis
- Reactivation of Hep B
- General Anesthesia
Albumin infusion seems to reduce renal failure and mortality in patients with SBP (Ann Emerg Med 2016;67(4):458)
TIPS Stenosis in the ED A transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneously-placed shunt between the hepatic vein and the portal vein thereby creating a low-resistance channel between the portal and systemic circulations. A TIPS is placed to reduce portal pressure in patients with complications related to portal hypertension (ie, variceal hemorrhage and ascites). For most patients, TIPS is successful initially, but over time shunts become stenotic or occluded. In two series of patients who underwent TIPS placement, by two years, virtually all surviving patients had developed TIPS stenosis (1,2). A patient who has undergone placement of a TIPS may present to the ED with an acute decompensation (e.g. worsening encephalopathy) which may be the result of TIPS stenosis. The Emergency Physician needs to be aware that the appropriate initial study to obtain is a RUQ ultrasound with doppler flow to evaluate the patency of the TIPS. It should be noted, however, that literature suggests that doppler sonography is relatively insensitive for detecting stent stenosis (3 – 5) – angiography is the gold standard – but it is a reasonable initial step in the ED. If TIPS stenosis is identified, the patient may be a candidate for a shunt revision. Hepatopulmonary syndrome is from dilation of pulmonary capillaries in lower portions of the lung. when they stand up they desaturate=platypnea Child’s classification(liver cirrhosis) The Child- Pugh classification is a means of assessing the severity of liver cirrhosis. Score 1 2 3 bilirubin (micromol/l) <34 34-50 >50 albumin (g/l) >35 28-35 <28 PT (s prolonged) <4 4-6 >6 encephalopathy none mild marked ascites none mild marked If there is primary biliary cirrhosis or sclerosing cholangitis then bilirubin is classified as <68=1; 68-170=2; >170=3. The individual scores are summed and then grouped as:
- <7 = A
- 7-9 = B
- >9 = C
A C classification forecasts a survival of less than 12 months. From: Pugh RNH, Murray-Lyon IM, Dawson JL et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:649-9.
high coags are not a contraindication to paracentesis (Grabau CM, et al. Performance standards for therapeutic abdominal paracentesis Hepatology 2004;40:484-8.)
TI Hepatocellular carcinoma presenting with intractable diarrhea. A radiologic-pathologic correlation. AU Steiner E; Velt P; Gutierrez O; Schwartz S; Chey W SO Arch Surg 1986 Jul;121(7):849-51. A 44-year-old woman with hepatocellular carcinoma presented with intractable watery diarrhea and her condition was evaluated angiographically. Surgical ablation of the tumor resulted in complete resolution of the diarrhea. The tumor cells of the hepatocellular carcinoma were found to contain vasoactive intestinal polypeptide, gastrin, and prostaglandinlike immunoactivity. To our knowledge, this is the first report of such an association. TI Diarrhea as a presenting symptom of hepatocellular carcinoma. AU Bruix J; Castells A; Calvet X; Feu F; Bru C; Sole M; Bruguera M; Rodes J SO Dig Dis Sci 1990 Jun;35(6):681-5. The clinical manifestations of hepatocellular carcinoma (HCC) are highly nonspecific since they usually mimic those of hepatic cirrhosis, which frequently underlies this neoplasm. The fact that some HCC patients present with severe diarrhea, an unusual symptom in liver cirrhosis, prompted us to determine the prevalence of diarrhea in a series of 23 consecutive HCC patients and compare it with that of a control group formed by cirrhotic patients without HCC, matched by age, sex, and etiology of the liver disease. All the patients were interviewed about the existence of diarrhea (defined as the presence of three or more loose stools per day appearing over three or more days) in the three months prior to admission. Both groups of patients were similar in regards to the degree of liver failure and presence of diarrhea-favoring factors. By contrast, diarrhea was significantly more frequent among HCC cases than among cirrhotics without HCC (47.8% vs 8.7%, P less than 0.005). HCC patients with diarrhea exhibited higher alkaline phosphatase and bilirubin levels and worse liver function, assessed by the Child-Pugh’s classification, than patients without diarrhea. However, neither tumor size, vascular invasion, or the degree of tumor differentiation were significantly different between these two groups of HCC patients. These results show that diarrhea is a frequent manifestation of HCC in patients with cirrhosis. Therefore, the development of HCC in these patients should be suspected upon the appearance of diarrhea. AD Department of Radiology, Hospital Clinic i Provincial, University of Barcelona, Spain.
Bleeding into Tumor
Biliary Tract Disorders
Antispasmodics Bentyl 20 mg PO QID or 20 mg IM (not IV) Q4-6 Glycopyrrolate 1-2 mg PO Bid/Tid or 0.2 mg IV/IM Tid/Qid
Pigmented stones vs. cholesterol stones (70% of stones) which are radiolucent Symptomatic known as biliary colic should resolve in a few hours Most sensitive test is HIDA or DISIDA scanning (morphine may increase specificity)
Common duct stones also are defined as retained, if discovered within two years of cholecystectomy, or recurrent if detected more than two years after cholecystectomy. Retained stones most likely were present at the time of cholecystectomy. IF mild disease without ultrasound CBD dilation precede with op otherwise consider ERCP or MRCP first Combination of bilirubin level > 3.0 and alkaline phosphatase >250: >75% chance of common duct stone (Surg Gynecol Obstet. 1982 Mar;154(3):381-4)
Having a fever is highly predictive. Murphy’s Sign has sensitivity of 97.2%. (Annals 28:3, 1996. p. 267) Acute cholecystitis gangrene: 59% lack fever 27% lack leukocytosis 6% lack fever and leukocytosis Acute cholecystitis nongangrene: 71% lack fever 32% lack leukocytosis 28% lack fever and leukocytosis Gruber PJ, et al. Ann Emerg Med. 1996 Sep;28(3):273-7 Does pt have cholecystitis? (JAMA 289(1):80, 2003) Murphy’s is pretty good (2.8 LR), Enzymes not useful. Epigastric was just as common as RUQ pain. Pain was constant more often than colicly. can see mild elevation in billi and amylase In this large, randomized trial, laparoscopic cholecystectomy within 24 hours of hospital admission was shown to be superior to the conservative approach concerning morbidity and costs. Therefore, we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients. (Ann Surg 2013;258:385–393)
3 days after chole consider bile leak bleeding, infection, damage to adjacent structures
occurs in 5-10% of patients with acute cholecystitis, tends to be more rapid and malignant. Patients frequently are elderly and have a history of diabetes mellitus. Other risk factors include multiple trauma, extensive burn injury, prolonged labor, major surgery, systemic vasculitic states, gallbladder torsion, and parasitic or bacterial infections of the biliary tract.
1% of cholecystitis cases diabetes is a risk factor need operation within 24 hours subtotal cholecystectomy it is better to remove 95% than 101% leave a 1cm rim of hartmann’s puch and sture buttress this over the cystic duct leave any friable posterior waal, oversew and blast with diathermy until you smell fried liver cholecystotomy can be open or perc use a large foley Mirizzi syndrome where an impacted cystic duct stone causes gallbladder distension and leads to hepatic duct compression Gall Bladder acalculous is a result of microcirculatory dysfunction. gram negative bacteria, occ. anaerobic infections, though rarely sole source 10% of AC will have assoc. choledocolithiasis these patients rarely have the assoc. complications of choledoco such as pancreatitis, cholangitis, or severe jaundice Since the patient was in her third trimester, she had an appointment with her obstetrician within the week, so I thought she could follow up. Jaundice in the third trimester is especially concerning. Conditions not to be missed are acute fatty liver of pregnancy (which can lead to fulminant liver failure) and intrahepatic cholestasis (which can lead to preterm labor). The former requires delivery, the latter monitoring, possibly as an inpatient. All pregnant patients with jaundice should be managed in conjunction with their obstetrician.
from biliary tract disease, gi tract infection, hematogenous spread via hepatic art, direct extension from intar-abd pathology, trauma e. coli, klebsiella, and proteus are the most common organisms
e. histolytica gains access by oral ingestion of contaminated food. cysts are digested and the trophozoites are released into the GI tract they then reach the liver via the portal system. can get indirect hemagglutination and gel diffusion precipitation secondary infection is the msot common complication treatment flagyl 750 mg tid for 7-10 days
Charcot’s Triad: RUQ pain, Fever, Jaundice. AMP/Gent/Flagyl or Mezlocillin the ruq pain is along the entire liver, not the murphy’s sign pan of AC ABX: Cipro/Flagyl, amp/gent/Flagyl, zosyn, unasyn, imipenem, ceftaz/Flagyl, aztreonam/clinda
Radiographic triad of SBO, pneumobilia, and ectopic gallstone 25% of non-strangulated SBO in pts > 65 cholecystoenteric fistula
Clot with superimposed infection of the portal vein Cirrhotics get pulmonary htypertension, they die during transplant operations
Alanine transaminase and aspartate transaminase
Alanine transaminase and aspartate transaminase are found in clinically important concentrations in:
- Liver (especially hepatocytes)
- Cardiac muscle
- Skeletal muscle
Their levels may be markedly elevated in hepatitic liver damage as well as in other disease, such as myocardial infarction. Very high levels (greater than 1000) are generally found only with:
- Drug induced hepatitis (especially paracetamol toxicity)
- Acute viral hepatitis (especially hepatitis A or B)
- Ischaemic hepatitis
- Severe acute autoimmune hepatitis (rarely).
Alcoholic hepatitis, chronic viral hepatitis (for example, hepatitis B or C), and fatty liver typically result in levels less than 100. The ratio of aspartate transaminase to alanine transaminase may be useful for distinguishing fatty liver due to alcoholic and non-alcoholic aetiologies.5
Big numbers generally = viral or drug
if Billi is superhigh in APAP, then good prognosis because very late to rise (hoffman)
Alkaline phosphatase largely originates from liver (mainly cells lining biliary ducts or membranes adjoining bile canniculae) and bone. Marked increases are typical of cholestasis (often with raised gamma glutamyl transferase – see below) or a variety of bone disorders (usually without raised gamma glutamyl transferase). Isoenzymes may be useful for distinguishing these sources.
Gamma glutamyl transferase
Gamma glutamyl transferase is found in hepatocytes and in biliary epithelial cells. Elevation typically indicates cholestasis or, when alkaline phosphatase is normal, induction of hepatic metabolic enzymes, often in response to long term exposure to excessive alcohol or drugs such as anticonvulsants or rifampicin.
Bilirubin is produced by haemoglobin catabolism. Elevation may indicate:
- Excess production following haemolysis or trauma
- Reduced levels of conjugation (for example, due to Gilbert’s syndrome)
- Hepatocyte failure
- Biliary obstruction.
High levels of unconjugated bilirubin, where other LFTs are normal, may identify haemolysis or Gilbert’s syndrome. Bilirubin is a powerful prognostic marker for chronic liver disease.6 It is useful for assessing a patient’s need for liver transplantation.7
Albumin is synthesised by the liver. Although low levels may indicate severe synthetic liver dysfunction, it is not a specific marker of liver disease and may fall acutely in severe illness, such as sepsis. The serum half life of albumin is 20 days, so it is not a good marker for acute liver injury. However, it may be useful for predicting prognosis and is a good synthetic marker for chronic liver disease.6
Although prothrombin time is not usually included in LFT panels, it is a highly important marker of prognosis in acute and chronic liver disease, once vitamin K deficiency or malabsorbtion have been ruled out (often by giving intravenous vitamin K).6 8 A BNORMAL LIVER FUNCTION TESTS G. Anton Decker, MD, Instructor of Medicine, Division of Gastroenterology, Hepatology, and Internal Medicine, Mayo Clinic College of Medicine, Scottsdale, Arizona Introduction: elevations in liver function tests (LFTs) often not pathologic; few conditions ( eg, acetaminophen [Tylenol] toxicity) require immediate action; spontaneous resolution common Case: man, 30 yr of age, asymptomatic with total bilirubin 2.5 mg/dL, direct bilirubin 0.1 mg/dL, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) within normal ranges; he drinks 1 glass of wine daily and takes no medications; ultrasonography of liver reveals no abnormal findings; diagnosis Gilberts syndrome; isolated unconjugated hyperbilirubinemia clue to diagnosis; syndrome occurs in 5% of population; hemolysis ruled out in healthy patients Liver function tests: ALT, AST, ALP, bilirubin
Curbsiders The Best of Liver Tests Notes
Liver chemistries include the enzymes of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase. These are markers of liver injury, not liver function!
Tests of liver function include the INR/prothrombin time, bilirubin, albumin and platelets. Albumin is a marker of longer term liver function as it is synthesized by the liver and has a half-life of 3 weeks (ACG Guideline 2017). Dr. Tapper also introduces a variety of tests that more closely evaluate hepatic metabolism including:
- 13-C Methionine breath test (Braden 2007)
- Ammonia clearance test by Shelia Sherlock (Shelia AASLD Obituary)- not recommended!
- Caffeine clearance test
Alkaline phosphatase & gamma-glutamyl transferase (GGT): alkaline phosphatase is a family of enzymes that are found in hepatocytes, bone, placenta, intestine and kidney. GGT is often suggested as a way to determine if alkaline phosphatase is coming from the liver, but Dr. Tapper describes how this is not always as helpful in clinical practice because GGT is “not specific for any one liver disease or even the liver itself” (Twitter thread by @ebtapper).
When evaluating a patient with acute liver injury, it is important to focus on a complete history and physical. Ask about ingestions including medications, supplements and anything new. Evaluate the timeframe of symptoms, lab abnormalities and ingestions.
Pattern of Injury
If it is not clear, the R score or ratio can be used to assess for a hepatocellular, cholestatic or mixed pattern of liver injury. The R ratio is equal to the patient’s ALT divided by the upper limit of normal (ULN) for the ALT over the patient’s alkaline phosphatase divided by the ULN for alkaline phosphatase. An R ratio >5= hepatocellular injury, <2=cholestatic, and 2-5=mixed (ACG Guideline 2017).
R= (ALT value / ALT ULN) / (alk phos/ alk phos ULN)
Dr. Tapper explains how the ratio of AST to ALT of 2:1 in alcohol related hepatitis is often taught but is not very sensitive or specific, particularly once the aminotransferase values are >1000. However, the degree of elevation in aminotransferases is helpful. Furthermore, if the (AST + ALT) > 500 the likelihood of the injury being caused by alcohol alone is low.
Hepatocellular injury: Common etiologies include drug-induced liver injury, autoimmune hepatitis and viral hepatitis. In hospitalized or very ill patients, consider ischemic hepatitis (often termed “shock liver”) or drug induced injury from acetaminophen.
Labs: check hepatitis A, hepatitis C, hepatitis B in most cases. If a transplant patient or recent chemotherapy consider CMV or other herpes virus. Test significant hepatitis for autoimmune hepatitis with an ANA, anti-smooth muscle antibody and IgG. Testing for hemochromatosis with an iron panel or for alpha-1-antitrypsin deficiency may be considered for chronic liver disease, but would not diagnose a new, acute injury. Similarly, most people do not have an indication for testing for Wilson’s disease initially which is rare and occurs more in children and younger adults.
Imaging: if liver injury, particularly if abdominal symptoms, get an ultrasound. If the index of suspicion is high for choledocholitiasis or you don’t have another source, consider cross-sectional imaging with MRCP.
Cholestatic injury: Common causes are biliary obstruction, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), sarcoidosis, common variable immunodeficiency (CVID), and DILI.
Labs: ANA, anti-smooth muscle antibody, IgG, anti-mitochondrial antibody (for PBC)
Imaging: ultrasound or MRCP to evaluate for biliary obstruction
These patients will often present with a strongly positive ANA, smooth muscle antibody (>1:80), and an elevated serum IgG several fold higher than the upper limit of normal. Note some labs may report F-actin by direct antigen testing, which is another lab technique that correlates with the titer of smooth muscle antibody tests. Consider referring these patients for a liver biopsy to determine diagnosis and need for immunosuppression. Note that drugs (like nitrofurantoin or minocycline) may trigger autoimmune hepatitis or present with a similar pattern of liver injury.
Drug-induced Liver Injury (DILI)
DILI is broadly defined as abnormalities in liver tests following introduction or continued use of a drug with other etiologies of liver injury excluded. Liver injury that occurs in a medication with a history of causing DILI should raise your suspicion. Dr. Tapper recommends LiverTox as a resource for information on prior reports of DILI with a specific drug exposure. DILI can also present with an autoimmune hepatitis picture, as above. The prognosis for DILI is worsened by an increased alkaline phosphatase elevation, bilirubin elevation, and prolonged time from ingestion of the drug to presentation with liver injury (Ashby 2021). Dr. Tapper usually follows stable patients regularly with labs until improvement or opts for a liver biopsy if concerned.
Isolated Lab Abnormalities
Alkaline phosphatase elevations
Elevations in alkaline phosphatase with symptoms such as pruritus should prompt additional workup with imaging (ultrasound first then consider MRCP). The differential for the etiology of includes biliary obstruction, infiltrative disease (including malignancy), primary biliary conditions (PBC or PSC), sarcoidosis, CVID, and DILI.
First, fractionate the total bilirubin. If >50% is direct= direct hyperbilirubinemia. Otherwise=indirect bilirubinemia. Usually with indirect hyperbilirubinemia 80-90% of bilirubin will be indirect. For indirect hyperbilirubinemia, check LDH, haptoglobin and reticulocyte count to evaluate for hemolysis. If there is no hemolysis, the diagnosis of Gilbert’s can be made. Usually, the total bilirubin in Gilbert’s disease will be <4mg/dL but certain factors including fasting, sleep deprivation and smoking can lead to further elevations due to decreased function of the remaining uridine-5′-disphosphate gluconyltransferase 1A1 (UGT1A1) (Shroff 2020).
Three main causes of liver disease in pregnancy: 1) non-pregnancy related causes 2) preeclampsia 3) intrahepatic cholestasis of pregnancy. About 1/3 of elevated liver enzymes in patients with pregnancy are intrahepatic cholestasis of pregnancy. Patients will usually present with pruritus, elevated alkaline phosphatase and an elevated serum bile salts level (Marschall 2019). It is important to trend and treat serum bile salt levels because the elevation in bile salts is related to outcomes in pregnancy (Ovadia 2019). The elevation in bile salts is related to outcomes in pregnancy with a level >40μmol/L associated with non-lethal adverse outcomes and > 100 μmol/L associated with stillbirth (Marschall 2019). Ursodiol and cholestyramine can be used for management, and repeat bile salt monitoring will be used to determine when to deliver.
Severe Acute Liver Injury and Acute Liver Failure
In the United States, most causes of an AST and/or ALT > 1000 IU/L (severe acute liver injury) are ischemic hepatitis, choledocholithiasis, DILI and acute viral hepatitis (Breu 2019). Ischemic hepatitis can occur in normotensive patients and generally occurs in persons with severe hepatic congestion or right heart failure. Acute liver failure is defined by a severe acute liver injury PLUS a significant coagulopathy (INR >1.5) AND hepatic encephalopathy (Bernal 2013). Acute liver failure is a very rare subset of acute liver injury usually caused by drugs (acetaminophen, antiepileptics, antimicrobials) or acute viral hepatitis.
Gas in the Liver