Internal Medicine 11: 45-Year-Old Male with Abnormal Liver Chemistries PDF

Internal Medicine 11: 45-year-old male with abnormal liver chemistries User: Sara Aldhaheri Email: [email protected] Date: February 2, 2025 11:26 AM Learning Objectives Explain/understand pathophysiology of conjugated and unconjugated hyperbilirubinemia. Describe the common...

Internal Medicine 11: 45-year-old male with abnormal liver chemistries User: Sara Aldhaheri Email: [email protected] Date: February 2, 2025 11:26 AM Learning Objectives Explain/understand pathophysiology of conjugated and unconjugated hyperbilirubinemia. Describe the common types of liver diseases and their risk factors (including inherited and acquired). Obtain an appropriate history to elicit risk factors for viral hepatitis. Use and be familiar with the AUDIT-C screening tool for alcohol use disorder. Identify when to order laboratory tests for evaluation of liver disease and when a liver biopsy might be indicated. Name a clinical decision support tool that could be applied to practice to reduce diagnostic errors. Knowledge Historical Features to Obtain in a Patient with Abnormal Liver Enzymes To begin the evaluation of elevated liver enzymes, a comprehensive history and physical should be performed to look for signs and symptoms of liver disease. The first tests that should be ordered are additional liver function tests to confirm the results are consistently elevated. It is important to note that the normal range for most laboratory tests is + or - 2 standard deviations. That means that 2.5% of all patients will have normal values above the upper limit of normal in the absence of disease. Historical elements that would be pertinent in a patient with abnormal liver enzymes would be: Jaundice and pruritus are common symptoms of cholestasis. Significant liver disease can be associated with weight loss and fever. Rectal bleeding can occur with liver disease due to portal hypertension in the hemorrhoidal veins. Dark brown urine due to urinary excretion of bilirubin Light-colored stools due to biliary obstruction Abdominal pain Diarrhea Increased abdominal girth Edema Nausea Vomiting, with or without hematemesis Altered mental status History Indicating Increased Risk of Liver Disease Regular alcohol use points towards alcohol-associated liver disease. Drinking greater than or equal to 3 drinks per day (greater than Alcohol use or equal to 21/week) in men and greater than or equal to 2 drinks per day (greater than or equal to 14/week) in women is considered disorder harmful drinking. Family A family history of liver disease may reveal a patient at risk for Wilson disease, hemochromatosis, alpha-one antitrypsin deficiency, history of and Gilbert syndrome. liver disease Blood Blood transfusions or solid organ transplant before 1992 and clotting factor transfusions before 1987 are risk factors for hepatitis C transfusions infection, as is occupational exposure to needle sticks from HCV-positive blood. Consumption of Consumption of uncooked HAV-contaminated food or water is a risk factor for acquiring hepatitis A. Common sources are fruit, contaminated shellfish, vegetables, ice and water. food © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 1/7  Diabetes mellitus increases the risk for metabolic dysfunction-associated steatohepatitis (MASH), formerly referred to as nonalcoholic Diabetes steatohepatitis (NASH) or metabolic dysfunction-associated liver disease (MASLD), formerly called nonalcoholic fatty liver disease mellitus (NAFLD). The actual risk of sexual transmission of hepatitis C is thought to be relatively low, likely much less than 1% per year among HIV monogamous couples. Transmission of hepatitis C among men who have sex with men (MSM) is most likely to occur with human immunodeficiency virus (HIV) co-infection. Injection drug use is the biggest risk factor for hepatitis C transmission. Hepatitis C is present in 50-90% of all persons with a history, Injection present or past, of injecting drugs. HIV is much less prevalent with reported rates of 2-3% of all users. Hepatitis C has a much greater drug use infectivity per injection. Hepatitis C risk is most associated with duration of injection use and with sharing of needles. Other important history includes vaccination history, specifically for hepatitis A and B. References Centers for Disease Control and Prevention (CDC). Integrated prevention services for HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use drugs illicitly: summary guidance from CDC and the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2012;61(RR-5):1-40. Considering Pretest Probability Pretest probability estimates the likelihood that a patient has a specific disease before diagnostic testing is performed. Many factors contribute to pretest probability including a patient's risk factors for a diagnosis and the prevalence of the disease in the community. Risk factors may include: Patient demographics (e.g., age) Lifestyle habits Occupational or environmental exposures Prior diagnoses Family history Disease prevalence may be particularly important with seasonal diseases like influenza. For some diagnoses, clinical prediction rules exist that combine multiple risk factors to help estimate the pretest probability of a diagnosis. Examples of clinical prediction rules include the Ottawa Ankle Rule to evaluate for ankle fracture and the Wells Criteria to evaluate for deep vein thrombosis (DVT). When a clinical presentation has multiple potential underlying causes, estimate the likelihood of each potential diagnosis, not just one diagnosis. This will help determine the more and less likely diagnoses and help guide diagnostic testing and treatment. Bilirubin Production & Metabolism Around 4 mg/kg of bilirubin is produced in the human body each day. Bilirubin is created from the normal breakdown of senescent red blood cells. The bilirubin metabolites are then conjugated by the liver, allowing secretion into bile for elimination. Measurement Measured bilirubin is divided into direct and indirect fractions. The direct fraction provides an approximation of the conjugated bilirubin. The indirect is the difference between the total and the direct and provides an estimate of the unconjugated bilirubin. Hyperbilirubinemia There are essentially three mechanisms by which bilirubin is elevated: 1. increased production Hemolysis increases the production of bilirubin and the resulting bilirubin is unconjugated. This process occurs in hemolytic anemias, hereditary spherocytosis, sickle cell disease, thalassemia, or G6PD deficiency. 2. intrahepatic causes Intrahepatic causes of hyperbilirubinemia are divided into those with unconjugated bilirubin and those with conjugated bilirubin. Elevation of unconjugated bilirubin is seen with Gilbert syndrome, a benign hereditary decrease in the enzyme glucuronosyltransferase that leads to decreased hepatocyte uptake of heme. Bilirubin in Gilbert syndrome tends to increase during stress, illness, dehydration, and fasting. The changes are transient and benign. Intrahepatic causes of conjugated hyperbilirubinemia are usually due to inflammation that disrupts bilirubin transport or due to hepatocyte dysfunction. This can be acute, as in the case of toxin injury, ischemic injury, drug injury, or acute viral hepatitis. It can be chronic, as is the case in chronic viral hepatitis, alcohol-associated hepatitis, Wilson disease, hemochromatosis, metabolic dysfunction-associated steatohepatitis (MASH), alpha-1-antitrypsin deficiency, and autoimmune hepatitis. There are two rare hereditary conditions that cause decreased excretion of bilirubin from hepatocytes: Dubin-Johnson syndrome and Rotor syndrome. Stasis of bile within the small bile ducts (intrahepatic cholestasis) can be caused by primary biliary cirrhosis, primary sclerosing cholangitis, drugs or toxins, granulomatous diseases, sepsis, pregnancy, viral or alcohol-associated hepatitis, malignancy, graft vs. host disease, or liver transplant. © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 2/7  3. posthepatic causes Finally, bilirubin metabolism is altered if there is obstruction of the bile drainage (extrahepatic cholestasis). This is seen in gallstones, tumors, primary sclerosing cholangitis, neoplasms, and pancreatitis. Hyperbilirubinuria Bile (mainly conjugated bilirubin) is converted to urobilinogen by intestinal bacteria. Most of the urobilinogen is excreted in feces or reabsorbed and transported back to the liver to be converted back into bile. The remaining urobilinogen (about 1% of total) is excreted in the urine. In patients with elevated serum bilirubin, only conjugated bilirubin will be present in urine. Hyperbilirubinuria is thus indicative of hepatobiliary disease, or rarely, inherited defects in excretion, such as Dubin-Johnson syndrome and Rotor syndrome. Acetaminophen Toxicity Acetaminophen toxicity is associated with acute liver hepatotoxicity with excessive ingestion, accidental or intentional. It is a dose-dependent toxin. In adults, toxicity can occur with acetaminophen doses of > 4 grams/day, although most cases occur in patients taking > 10 grams/day. Medications That Commonly Cause Elevated Aminotransferases Atorvastatin, a statin, has been reported to elevate liver enzymes by 0.5% to 3%. This elevation usually occurs within the first three months of therapy and is dose-dependent. In 2012, the U.S. Food and Drug Administration (FDA) no longer recommended routine monitoring of liver enzymes after starting statins, as this does not appear to be effective in detecting or preventing serious liver injury. Aminotransferase levels should be obtained before starting statin therapy and then only as clinically indicated thereafter. Anti-epileptic medicines, including phenytoin and carbamazepine, also cause elevated liver enzymes. Other medications associated with liver injury include isoniazid, ketoconazole, and NSAIDs (though NSAID-induced hepatotoxicity is very rare). Ask all patients about the use of herbal and over-the-counter medicines. Liver enzymes can be increased with many herbal remedies, including chaparral, ephedra, lady's mantle, senna, shark cartilage, and skullcap herb. Liver enzymes can also be increased with the use of anabolic steroids, cocaine, PCP, etc. These types of uses should be asked about if no other explanation is found for elevated liver enzymes. Metabolic Dysfunction-Associated Steatohepatitis Metabolic dysfunction-associated liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) resembles the inflammation of alcoholic liver disease but occurs in the absence of alcohol use. Obesity, male sex, diabetes mellitus, & hyperlipidemia Risk factors Of patients with both obesity and diabetes mellitus, nearly all will have mild liver inflammation, 50% will have steatohepatitis, and 19% will have cirrhosis, making these diagnoses the most common causes of cirrhosis in the United States and other industrialized nations. Some studies have reported male sex has an increased risk while other studies suggest female sex may have an increased risk. Symptoms Most of the patients are asymptomatic and diagnosis is suspected from abnormal aminotransferases. Studies The liver will show fatty infiltration on ultrasound. The diagnosis is suspected by the clinical picture and imaging. Diagnosis Confirmation and staging can be accomplished with liver biopsy. Lifestyle modifications, particularly low fat diet, weight loss and exercise. Management Pioglitizone has been shown to reduce the deposition of fat in the hepatocytes. Use can be considered in patients with MASH, though with careful consideration of the potentially significant medication side effects and risks. Genetic Liver Diseases That Cause Elevated Aminotransferases Alpha-1 antitrypsin deficiency Alpha-1 antitrypsin deficiency is a cause of emphysema in young individuals. It is also a rare cause of elevated liver enzymes. Associated findings: It is associated with a low level of the alpha-1 antitrypsin enzyme. Diagnosis: Genetic tests confirm the condition. Hemochromatosis Hemochromatosis is a genetic multi-organ iron deposition disorder. It is associated with bronzing of the skin, diabetes mellitus, liver disease, heart failure, hypogonadism, and arthritis. All of these symptoms are due to an autosomal recessive genetic defect of the HFE gene. It occurs with a frequency of 5:1,000 in patients of European descent. Associated findings: Hemochromatosis is associated with an extremely elevated ferritin level (>1000 ng/mL), but ferritin is an acute-phase reactant, meaning it will increase with any acute stress on the body. Screening: Initial screening should include iron studies, which looks for the presence of iron overload. This includes serum iron, serum transferrin, transferrin saturation (ratio of iron to transferrin). A transferrin percentage greater than 45% is very suggestive of disease. © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 3/7  Diagnosis: Genetic testing is necessary to confirm the diagnosis. In the past, liver biopsy was required, but this has been largely replaced with genetic testing. Wilson disease Wilson disease is a genetic disorder of biliary copper excretion leading to copper deposition in the liver and other organs. Associated findings: It usually presents in young adults with asymptomatic elevation of liver enzymes and can progress to neuropsychiatric changes as the patient ages. Kayser-Fleischer rings are as a result of copper deposition in the peripheray of the cornea and are usually seen on eye examination. Screening: The initial screening tests are ceruloplasmin and a 24-hour urinary copper. The ceruloplasmin which should be decreased and the 24-hour urinary copper should be >40 mcg/24 hours. Diagnosis: If the initial tests are inconclusive, a liver biopsy may be done. Genetic testing may be utilized if the liver biopsy proves to be inconclusive. Autoimmune Hepatitis More common in: females than males people with other autoimmune diseases However, since it can have an indolent course, it should be considered in a patient with asymptomatic liver enzyme elevations. Alcohol-Associated Liver Disease Alcohol-associated liver disease is a spectrum from fatty liver -> alcohol-associated hepatitis -> alcohol-associated cirrhosis. Fifteen to twenty percent of people who participate in harmful drinking of alcohol chronically can develop hepatitis, cirrhosis, or both. It usually requires six to eight drinks a day for several years to develop. Females require much less and are more susceptible. Hepatitis C also dramatically increases the rate of alcohol injury to the liver. Alcohol-associated hepatitis is associated with fatigue, anorexia, and weight loss. It can eventually lead to portal hypertension, GI bleeding, ascites, and hepatic encephalopathy. Cirrhosis can occur before, with, or after hepatitis. Interviewing Patients About Alcohol Use AUDIT-C The Alcohol Use Disorders Identification Test (AUDIT)-C is another screening test that may be used to obtain more information about a patient's alcohol consumption. 1. How often do you have a drink containing alcohol? 2. How many drinks containing alcohol do you have on a typical day when you are drinking? 3. How often do you have six or more drinks on one occasion? Scores considered positive for unhealthy drinking are: Three or more in women Four or more in menThe Alcohol Use Disorders Identification Test (AUDIT) utlizes 10 items to screen for harmful drinking.Learn more about this at AUDIT. Interpreting Hepatitis Serologies The presence of the hepatitis C antibodies confirms exposure to the virus in the past. The actual antibody titer does not tell you if the patient is chronically infected with hepatitis C; this serology stays positive even if the infection was spontaneously cleared by the body. The presence of chronic infection is confirmed with hepatitis C virus RNA titers. Hepatitis C is an RNA virus, in contrast to hepatitis B, which is a DNA virus. Hepatitis B e-antigen is used in the evaluation of chronic hepatitis B to determine the activity of the virus. There are situations where a negative antibody to hepatitis C virus (HCV) cannot exclude infection. These include acute HCV or HCV in immunosuppressed patients, such as patients with HIV and those on hemodialysis. HCV antibodies are present about eight weeks after infection. RNA levels become detectable one to two weeks after infection. If immunosuppression or acute infection is suspected, RNA levels should be ordered to rule out infection. A negative HCV RNA test indicates that the infection has resolved. Read the recommendations for testing, managing, and treating hepatitis C from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. http://www.hcvguidelines.org/. Hepatitis Prognosis Hepatitis C The course of hepatitis C is variable, but approximately 80% of all people who get the virus will have chronic infection. Of the patients with chronic © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 4/7  infection, 20% will develop cirrhosis, or scarring of the liver. Once a patient has cirrhosis, 1-4% will develop hepatocellular carcinoma, a cancer of the liver, every year. The time for progression from acute infection to cirrhosis is approximately 20 years, but the acute infection is rarely diagnosed because it is asymptomatic. Hepatitis C is often diagnosed years after initial infection. The rate of progression is affected by certain prognostic factors. Good prognostic signs: female sex and younger age of infection. Poor prognostic signs: male sex, later age of infection, alcohol use disorder, obesity, and concomitant infection with HIV. Hepatitis B with hepatitis C together dramatically accelerates the risk of cirrhosis. Hepatitis B The likelihood of acute hepatitis B to become chronic depends upon the age at which someone becomes infected. The younger a person is when infected with hepatitis B virus, the greater the chance of developing chronic hepatitis B. Approximately 90% of infected infants and 25%-50% of children infected between the ages of 1 and 5 years will develop chronic hepatitis B. The risk drops to 6%-10% when a person is infected over 5 years of age. Worldwide, most people with chronic hepatitis B were infected at birth or during early childhood. For more information, see: CDC. Hepatitis B FAQs for the Public. https://www.cdc.gov/hepatitis/hbv/bfaq.htm#bFAQ09. Accessed February 19, 2024. Management Hepatitis C - Secondary Prevention Instructions for patients with Hepatitis C 1. Abstain completely from all illicit drugs and alcohol. The combination of alcohol and hepatitis C dramatically speeds up cirrhosis. 2. Be aware of medicines like acetaminophen that are cleared by the liver. Only take acetaminophen sparingly. 3. Vaccination against hepatitis A and B. 99% to 100% of adults have protective levels of hepatitis A antibody five-eight years after receiving two doses of vaccine. Chronic Hepatitis C Treatment Initial teatment of hepatitis C includes newer direct-acting antivirals (DAA), which were FDA approved in 2016. Genotype 1: Daily fixed-dose combination of glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. Genotypes 2 & 3: Daily fixed-dose combination of glecaprevir/pibrentasvir or sofosbuvir/velpatasvir Genotype 4: Daily fixed-dose combination of glecaprevir/pibrentasvir, ofosbuvir /velpatasvir, fixelbasvir/grazoprevir, or ledipasvir/sofosbuvir Genotypes 5 & 6: Daily fixed-dose combination of a combination of glecaprevir/pibrentasivir, sofosbuvir/velpatasvir, or ledipasvir/sofosbuvir While these medications are life saving, they are also extremely expensive- sometimes prohibitively expensive if the patient lacks insurance. It is important to seek ways to help patients obtain the medications when they are indicated. Guidelines from the American Association for the Study of Liver Diseases and Infectious Diseases Society. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. https://www.hcvguidelines.org. Accessed Febrauary 19, 2024. Many of these medications used in the treatment of hepatitis C may interact with other medications. Prior to initiating therapy, verify medications do not interact with a patient's other medications. https://www.hep-druginteractions.org Accessed February 19, 2024 Studies Liver Chemistries A detailed history that includes diet, prescriptions, over-the-counter medications and supplements, along with a thorough physical examination can help us decide which liver chemistries to order. The pattern of the liver chemistry abnormalities may often identify the cause of the liver disease. Commonly ordered liver chemistry tests include: Bilirubin Aspartate transaminase (AST, formerly referred to as serum glutamic-oxaloacetic transaminase, SGOT) Alanine transaminase (ALT, formerly called serum glutamic-pyruvic transaminase, SGPT) Gamma-glutamyl-transferase (GGT) Alkaline phosphatase AST and ALT are excellent markers of hepatocellular injury. AST is also found in non-hepatic sources such as skeletal and cardiac muscle, kidney © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 5/7  and brain while ALT is found primarily in the liver. Common causes of elevated AST and ALT include nonalcoholic and alcoholic fatty liver disease, hepatitis A, B and C, autoimmune liver disease, hemochromatosis and Wilson disease. An AST/ALT ratio greater than 2 may suggest alcoholic liver disease, especially when the GGT is elevated. The AST, ALT, and alkaline phosphatase tests can be helpful to distinguish between hepatocellular and cholestatic disease. The American College of Gastroenterology (ACG) has developed Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Evaluating for Autoimmune Hepatitis Autoimmune hepatitis has a female-to-male predominance of 4:1. It is more common in patients with other autoimmune diseases (type 1 diabetes mellitus, thyroiditis, etc.). It leads initially to indolent liver inflammation and elevated aminotransferases and can progress to acute liver failure. The actual level of aminotransferases is not helpful as they can start out with minor elevations and increase with time. A screening test for autoimmune hepatitis would show elevated serum globulins, usually twice normal. Elevated globulins are sensitive but not specific, and should be followed by further testing. There are two types of autoimmune hepatitis. Type I autoimmune hepatitis is associated with high levels of ANA and anti-smooth muscle antibody. Type II autoimmune hepatitis is a much rarer disorder and is associated with elevated levels of anti-liver kidney microsomal-1 antibody (anti-LKM-1 ab) alone or occurs with anti-liver cytosol-1 antibody (anti-LC-1 ab). All of these autoantibodies have a low sensitivity and specificity for the disease. The only definitive diagnostic test is liver biopsy. Diagnosis is critical because the majority of cases will respond to treatment with prednisone or azathioprine. Liver transplant is an option for patients who fail treatment. Alcohol-Associated Hepatitis Liver Enzyme Pattern Alcohol-associated hepatitis is commonly associated with AST twice that of ALT (80% of patients). This pattern is due to low serum activity of alanine aminotransferase (ALT) because of alcohol-related decrease in pyridoxal 5-phosphate activity. It is rare to have transaminases greater than 10 times the upper limit of normal. The level of aminotransferases does not correlate with degree of hepatitis. The level of bilirubin and prothrombin time, in contrast, do correlate with degree of liver injury. Recommended Workup of Suspected Hepatitis or Alcohol-Associated Liver Disease Prothrombin Time and Prothrombin time may be prolonged and albumin may be reduced if the liver is not synthesizing proteins adequately. Albumin If there is a history of injection drug use or has ever engaged in sexual intercourse, the patient should be tested for HIV. HIV is HIV commonly co-transmitted with hepatitis C among injection drug users and to a lesser extent sexual contact. To identify hemochromatosis, iron studies—consisting of serum iron, serum transferrin, transferrin saturation, and ferritin—should be Iron studies part of the initial evaluation of elevated aminotransferases. Right upper A right upper quadrant ultrasound is often quite helpful in evaluating the presence of cirrhosis (small, nodular liver) and abnormalities quadrant of the biliary tree. If the suspicion for biliary disease is low, then other tests, such as viral serologies, would be ordered first; but ultrasound ultrasound is a reasonable choice after you have confirmed that the liver chemistries are indeed abnormal. If there is a history of injection drug use, it is very likely that the cause of the elevated enzymes is viral hepatitis. Approximately 4.1 Viral million Americans are positive for antibodies to hepatitis C and 2.4 million are HCV RNA positive. The initial evaluation for viral hepatitis hepatitis should be serologic testing, which is 92-97% sensitive. Initial serology is usually done as a panel for hepatitis A, B, and C. serology The initial testing for hepatitis B is for the surface antigen, surface antibody, and core antibody. A CBC should be included in the initial evaluation of abnormal aminotransferases, if it has not already been completed. Studies not indicated at this time Antimitochondrial antibody Antimitochondrial antibody testing can be useful when evaluating for primary biliary cirrhosis, but this primarily causes testing elevation of bilirubin and alkaline phosphatase. Computed tomography Computed tomography (CT) would be more helpful for evaluating for a liver mass. (CT)( Erythrocyte sedimentation An erythrocyte sedimentation rate (ESR) is a very non-specific indicator of inflammation and would not be helpful in rate (ESR) determining the cause of elevated transaminases. A liver biopsy is sometimes used in the workup of liver dysfunction; however, given its invasive nature, it is usually one of the last diagnostic tests performed. Liver biopsy may be especially useful in cases where diagnosis is uncertain or in Liver biopsy cases of suspected autoimmune hepatitis, metabolic dysfunction-associated steatohepatitis (MASH), or infiltrative diseases such as sarcoidosis or other granulomatous diseases such as tuberculosis. © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 6/7  Magnetic resonance If alkaline phosphatase and bilirubin were elevateds, then evaluation of the biliary tree would be appropriate. Ultrasound cholangiopancreatography should be the first imaging test in that setting. If unrevealing, a magnetic resonance cholangiopancreatography (MRCP) (MRCP) can provide additional imaging non-invasively. However, a MRCP is more expensive than an ultrasound. The Role of Liver Biopsy The role of liver biopsy in hepatitis C is no longer recommended. Many experts feel that if the need for treatment is clear, liver biopsy is not necessary. Liver biopsy is associated with risks and sampling error may underestimate the degree of fibrosis. The result of the biopsy may not change the decision to treat the patient. Indications for liver biopsy would be: diagnosis of Wilson disease hemochromatosis diagnosis of liver masses evaluation of abnormal aminotransferases in patients with inconclusive workup evaluation of the liver after transplantation Risks The most severe risk of liver biopsy is intraperitoneal bleeding and large liver hematomas. Mortality from a biopsy is 1 out of every 10,000-12,000 patients. Other potential complications include pain, hypotension, pneumothorax, hemothorax, and hemobilia. Clinical Reasoning Differential of Abnormal Liver Chemistries in a Patient with Injection Drug and Alcohol Use More Likely Diagnoses A history of injection drug use increases the risk of viral hepatitis including hepatitis B and C. Hepatitis B and C can be transmitted through reused tattoo needles or needles for injection drug use. Many liver diseases would have a normal physical examination early in the course of the disease. For this reason, viral hepatitis is often not identified for years after its acquisition. Hepatitis B &C Note: The USPSTF also recommends all adults aged 18 to 79 years be screened for hepatitis C. Vaccination for hepatitis B has decreased the rates of infection. There is no vaccination available for hepatitis C and the majority of new cases are in injection drug users. Alcohol- associated Alcohol-associated liver disease is fairly common and should be considered given a history of alcohol and substance use. Note, liver alcohol-associated liver disease usually presents with AST>ALT. disease Less Likely Diagnoses Acetaminophen (Tylenol) toxicity is a consideration, though this is usually associated with extremely elevated aminotransferases (in the thousands). It can also cause an acute hepatitis with jaundice and loss of synthetic function, such as the ability to make albumin and clotting factors. It is usually much more symptomatic. Autoimmune hepatitis is more common in females and is often associated with a family history of liver disease. Hemochromatosis is a genetic disorder causing abnormal iron deposition in organs and can cause mild elevation in transaminases as seen here but is quite rare. Symptoms are due to an autosomal recessive genetic defect of the HFE gene. It occurs with a frequency of 5:1,000 in patients of European descent. If more common diagnoses are ruled out it could be considered. Metabolic dysfunction-associated steatohepatitis (MASH)more commonly occurs in patients with obesity and/or diabetes mellitus. Metastatic liver cancer is unlikely with no evidence for another primary cancer. Hepatitis A would not cause chronic viral hepatitis. References Rinella, Mary E.1; Neuschwander-Tetri, Brent A.2; Siddiqui, Mohammad Shadab3; Abdelmalek, Manal F.4; Caldwell, Stephen5; Barb, Diana6; Kleiner, David E.7; Loomba, Rohit8. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77(5):p 1797-1835, May 2023. | DOI: 10.1097/HEP.0000000000000323 U.S. Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Accessed September 28, 2021. © 2025 Aquifer, Inc. - Sara Aldhaheri ([email protected]) - 2025-02-02 11:26 +04 7/7