The Toxic Side: Unveiling Acetaminophen’s Adverse Repercussions (Case Study) - 2024

1 The Toxic Side: Unveiling Acetaminophen’s Adverse Repercussions _____________________ A Case Study Presented t...

1 The Toxic Side: Unveiling Acetaminophen’s Adverse Repercussions _____________________ A Case Study Presented to The Department of Pathology and Laboratories Mariano Marcos Memorial Hospital and Medical Center _____________________ In Partial Fulfillment of the Requirements for Clinical Internship _____________________ AUTHORS: Lord Kent G. Collado, Nelcy D. Delos Santos, Sarah Jane D. Ibañez, Gian Aubrey B. Irigayen, Cindy Joyce B. Lazo, Joyce Ann S. Pasion, Jianne Cristy B. Pio, Audrey G. Talay, Kiara Maica M. Vidal ADVISER: Erwin D. Mandac, RMT August 2024  2 ABSTRACT This case study explores the intricate diagnostic challenges associated with Acetaminophen toxicity and its distinction from other similar illnesses. Acetaminophen toxicity occurs relatively frequently and reports that acetaminophen is one of the most common pharmaceuticals associated with both intentional and unintentional poisoning and toxicity. Acetaminophen is commonly considered safe OTC drug; hence, it is extremely important to advise patients of the potential risks associated with its inappropriate use. Hepatitis B, Ischemic hepatitis, and Acetaminophen toxicity were the differential diagnoses considered. The primary objective of this case study was to make well-supported inferences and determine an accurate diagnosis based of the patient’s condition. This involved a structured analysis of patient’s history, medication history, a consideration of various potential diagnoses, and a detailed examination. The potential diagnoses considered by the examination results provided involve a) abdominal pain, b) nausea and vomiting, c) flu-like illness, d) jaundiced with scleral icterus, e) tenderness of the abdominal right upper quadrant f) over medication history. Other significant features also presented: a) highly elevated AST and ALT, b) elevated total and direct bilirubin, c) prolonged prothrombin time and INR, d) hepatocellular necrosis, e) parenchymal collapse, f) hepatocyte dropout, g) ballooning degeneration, h) fibrosis, i) ascites j) non-reactive HBsAg, k) normal spleen. Keywords: hepatocellular necrosis, Hepatitis B, pharmaceuticals, poisoning, jaundice  3 I. INTRODUCTION Acetaminophen, also known as paracetamol and N-acetyl-p-aminophenol (APAP), is one of the most commonly used oral analgesics and antipyretics. It is a common constituent in many over-the-counter (OTC) and prescription medications and can also be used with other active chemicals to treat allergies, coughs, colds, flu, and insomnia. One of the most frequently used is Tylenol. However, overconsumption of this type of medication can lead to hepatotoxicity or drug- induced liver injury (DILI) which can result in a range of problems, including abnormalities in liver function, acute liver failure, and even death. (U.S. Food & Drug Administration, 2022). Acetaminophen toxicity is prevalent, due to the medication's widespread availability and the assumption that it is extremely safe. In the United States, it is one of the most common origins of both intentional and unintentional poisoning, becoming the proximate cause of acute liver failure and the second most prevalent cause of liver failure requiring transplantation. Although these effects, warnings, and associations have been documented, acetaminophen remains a safe and effective medication when used accurately according to Gerriets, et al., (2024). People with underlying liver disease or those with chronic alcohol consumption are at an increased risk of developing hepatotoxicity with use of acetaminophen. The maximum recommended acetaminophen dosage is 4 grams/day in an adult and 90 mg/kg/day in children (Farrel, 2024). Moreover, the hepatotoxicity observed with acetaminophen use usually corresponds to high doses that surpass the recommended maximum dose. This effect may be also associated with the consumption of multiple drug products containing acetaminophen as an ingredient. This can occur purposefully (when a person knowingly takes more than the recommended maximum daily dose) or accidentally (when a person is unaware, they are taking multiple products containing acetaminophen and exceeds the recommended maximum daily dose). As stated by Anderson, et al., (2024), nausea, vomiting, stomach pain, loss of appetite, tiredness, pain in the upper right side, and jaundice are some of the common signs and symptoms that happen during acetaminophen toxicity. Likelihood and severity of hepatotoxicity caused by an acute ingestion can be predicted by the amount ingested or, more accurately, by the serum  4 acetaminophen level. Liver tests are done and in suspected severe poisoning, prothrombin time is measured. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) results correlate with the stage of poisoning. AST levels greater than 1000 IU/L are more likely to result from acetaminophen poisoning than from chronic hepatitis or alcoholic liver disease. If poisoning is severe, bilirubin and international normalized ratio may also be elevated. (O'Malley, 2022). In this case study, a patient was described as having a severe abdominal pain, nausea, and vomiting. Through a structured analysis of the patient's history, differential diagnosis, and examinations, the main goal of this case study was to draw well-supported conclusions and arrive at an accurate diagnosis based on the patient's condition.  5 II. CASE PRESENTATION PATIENT PRESENTATION John Doe presented to the emergency department with complaints of severe abdominal pain, nausea, and vomiting for the past 24 hours. He reported a recent flu-like illness but denied any significant changes in his diet or medication regimen. Upon examination, John appeared jaundiced with scleral icterus. Abdominal palpation revealed tenderness in the right upper quadrant. Upon further questioning, it was revealed that John had been experiencing persistent headaches over the past week and had been self-medicating with painkillers such as Tylenol, Panadol, and Ibuprofen and admitted to taking up to 4 grams daily. John was immediately admitted to the intensive care unit (ICU) for close monitoring and supportive care. Despite aggressive medical management, John's liver function continued to deteriorate rapidly over the next 48 hours. He developed hepatic encephalopathy and required intubation for airway protection. Unfortunately, due to the severity of liver failure and multi- organ dysfunction syndrome, John passed away within 72 hours of admission. Table 1 Complete Blood Count Patient Reference Range Unit WBC 8.50 4.80 – 10.80 x109/L RBC 4.57 3.80 – 5.50 x1012/L Hgb 14.50 12.00 – 15.20 g/dL Hct 42 37 – 46 % PLT 180 140 - 450 x109/L  6 Table 2 Differential Count and Coagulation Studies Patient Reference Range Unit Neutrophils 65 30 – 70 % Lymphocytes 25 20 – 50 % Monocytes 7 2 – 12 % Basophils 1 0–2 % Prothrombin Time 22 11.00 – 13.00 seconds INR 2.30 0.80 – 1.10 Table 3 Blood Chemistry Patient Reference Range Unit Creatinine 1.00 0.70 – 1.30 mg/dL BUN 18 8.00 – 22.00 mg/dL ALT 2100 6.00 – 37.00 U/L AST 2350 5.00 – 37.00 U/L Albumin 3.20 4.80 – 5.20 g/dL Bilirubin, total 8.50 0.20 – 1.00 mg/dL Bilirubin, direct 6.20 < 0.30 mg/dL Sodium 138 135 – 145 mmol/L Potassium 4.00 3.50 – 5.00 mmol/L Chloride 102 98 – 106 mmol/L Bicarbonate 24 22 - 28 mmol/L Table 4 Hepatitis Panel Patient HBsAg Negative HBsAg antibody Reactive HBeAg Negative HBcAg antibody Negative HBV DNA Not detectable HAV antibody Negative HCV antibody Negative  7 Liver Biopsy: Microscopic Description: The submitted liver biopsy specimen consists of multiple fragments of liver tissue, predominantly showing extensive hepatocellular necrosis and loss of architecture. There is marked parenchymal collapse with hepatocyte dropout and ballooning degeneration. Scattered areas of inflammatory infiltrates, primarily lymphocytes and occasional neutrophils, are noted around areas of necrosis. Mallory-Denk bodies, indicative of alcoholic liver disease, are not identified. Histopathological Findings: Hepatocellular Necrosis: Extensive necrotic areas involving both lobular and portal regions. Inflammatory Infiltrates: Mild to moderate lymphocytic infiltrates with scattered neutrophils. Ballooning Degeneration: Seen in surviving hepatocytes adjacent to necrotic areas. Fibrosis: Early periportal fibrosis noted, consistent with ongoing hepatic injury and repair. Special Stains: Iron Stain: Negative for iron deposition. Trichrome Stain: Demonstrates early periportal fibrosis. Immunohistochemistry: CD68: Mild to moderate increase in Kupffer cells. Computed Tomography Scan Liver: The liver is enlarged with diffusely decreased attenuation, suggestive of parenchymal edema and early cirrhosis changes. There is mild to moderate ascites noted. Biliary System: No evidence of biliary obstruction or dilatation. Spleen: Normal size and attenuation. Pancreas and Kidneys: Unremarkable. Abdominal Lymph Nodes: No significant lymphadenopathy.  8 III. ANALYSIS OF DATA This section presents an in-depth analysis of the differential diagnoses and their significant correlation to the laboratory values presented by the case. In, addition, this section also explains the diagnostic process and how the researchers came up with the final diagnosis. The diagnosis was determined based on the provided laboratory values, patient symptoms, medications used, and general patient examination. Differential diagnosis was rules out using the same criteria. The following disorders are considered in the differential diagnosis: a. Hepatitis B b. Ischemic Hepatitis c. Acetaminophen Toxicity  9 Differential Diagnosis The figure below illustrates a schematic diagram for figuring out the diagnosis of the patient presented in this case. The figure consists of differential diagnoses containing the clinical basis for both their case association and ruling out. Figure 1 Guide for Diagnosis  10 AST, Aspartate Aminotransferase; ALT, Alanine Aminotransferase; HBsAg, Hepatitis B Surface Antigen; INR, (International Normalized Ratio The researchers included Hepatitis B, Ischemic Hepatitis, and Acetaminophen Toxicity as a differential diagnosis based on the typical presentation demonstrated in the case study: Patient Presentation: “John Doe presented to the emergency department with complaints of severe abdominal pain, nausea, and vomiting for the past 24 hours. He reported a recent flu- like illness but denied any significant changes in his diet or medication regimen. Upon examination, John appeared jaundiced with scleral icterus. Abdominal palpation revealed tenderness in the right upper quadrant.” Figure 2 Patient Presentation CDC – Food safety. (2024, April 29). Digestive Health UK – Nausea and Adobe – High Fever (2024). https://www.cdc.gov/food- Vomiting (2024). https://stock.adobe.com/ph/sear safety/signs-symptoms/index.html https://digestivehealthuk.com/sy ch?k=high+fever mptom/nausea-and-vomiting/ GoodRX Health – Causes of Jaundice Medmastery – Abdominal Examination (2022, March 15). (2021, February 22). https://www.goodrx.com/health- https://www.medmastery.com/guides topic/liver/causes-of-jaundice /abdominal-examination-clinical- guide a. Abdominal pain. b. Nausea and Vomiting. c. The patient experienced flu-like illness. d. Jaundiced with scleral icterus. e. Tenderness of the abdominal right upper quadrant.  11 HEPATITIS B Hepatitis B is an infection which affects the liver and is caused by the hepatitis B virus (HBV). It is a significant global health concern, with approximately 257 million people living with chronic hepatitis B infection worldwide. Understanding the hepatitis b causes, signs of hepatitis b, and prevention of this viral infection is crucial for promoting public health and reducing its impact on individuals and communities. To effectively address hepatitis B, it is essential to grasp the key aspects of the infection. HBV is a bloodborne disease. Sexual contact contaminated bodily fluids, mother-to- 11 child transmission during childbirth, and contaminated blood or body fluids are just a few of the ways the Hepatitis B virus (HBV) can spread. However, remember that casual contact, such as hugging, sharing utensils, or sneezing, does not spread hepatitis B. (Pathkind Labs, 2023) Hepatitis B can manifest as either acute or chronic infection. Acute hepatitis B refers to a short-term illness that typically lasts a few weeks to several months. In the early stages of acute hepatitis B, people may experience flu-like symptoms like: Fatigue, fever, muscle aches, and loss of appetite. As the infection progresses, jaundice becomes a prominent symptom. Jaundice makes the skin and whites of the eyes turn yellow, along with dark urine and pale-coloured stools. Other signs of hepatitis b may include Nausea, vomiting, abdominal pain, and a general feeling of being unwell. Chronic hepatitis B occurs when the virus persists in the body for more than six months. Chronic infection is often asymptomatic, meaning individuals may not experience any noticeable signs of hepatitis b for an extended period. However, long-term effects can be severe, including liver cirrhosis, liver failure, and a heightened risk of developing liver cancer. (Pathkind Labs, 2023) Detection of IgM for hepatitis B core antigen (HBcAg) in serum is required to make the diagnosis of acute Hepatitis B Virus (HBV) infection. Hepatitis B surface antigen (HBsAg) may be present in acute infection or in patients who are chronic carriers. Its presence in patients with symptoms of acute hepatitis strongly suggests acute HBV infection but does not rule out chronic HBV with acute superinfection by another hepatitis virus. The presence of HBsAg in the serum for 6 months or longer indicates chronic infection (Samji, 2023). Moreover, an increased ALT and  12 AST level is often a sign of liver disease that includes hepatitis. Liver disease is even more likely when the levels of substances checked by other liver blood tests have also increased (Mount Sinai Health System, 2024). Elevated bilirubin levels in hepatitis B infection result primarily due to liver dysfunction, which affects bilirubin metabolism and excretion (Samji, 2023). Moreover, prothrombin time (PT) can be prolonged, indicating impaired blood clotting function. This is due to the liver's role in synthesizing clotting factors, including prothrombin (which is also known as factor II). Hepatitis B virus (HBV) can cause inflammation and damage to hepatocytes (liver cells), leading to decreased production of clotting factors. As liver function deteriorates, the synthesis of prothrombin and other clotting factors may be compromised, resulting in a longer PT (Sharma & Nagalli, 2023). In the liver biopsy result of acute hepatitis B, there is inflammatory cell infiltration and variable involvement of portal inflammation. Plasma cells may also be prominent, and a few neutrophils and eosinophils may be present. In addition, compared to acute hepatitis C, acute hepatitis B has periportal inflammation. Occult infection and mild portal inflammation, focal necrosis, apoptosis, and fibrosis may persist following clinical recovery. Ballooning degeneration is also seen as a more severe degree of cell swelling (Guzman & Vyas, 2024). On the other hand, hepatocytes in chronic hepatitis B also often exhibit distinct changes. When hepatitis B surface antigen (HBsAg) is elevated or during active viral replication, hepatocytes may display a glassy appearance in their cytoplasm. This appearance is due to the accumulation of viral components. Additionally, there can also be marked variation in hepatocyte nuclei size and appearance, along with close contact between hepatocytes and lymphocytes. Histologically, enlargement of portal tracts due to mononuclear cell infiltration and lobular spotty necrosis are common findings. Hepatocyte death, atrophy, regeneration, and fibrosis are also prominent features of chronic hepatitis B progression, reflecting ongoing liver injury and repair processes (Guzman & Vyas, 2024). A lot of the signs and symptoms that were seen in the case were related to Hepatitis B infection. Also, with the chemistry result, the ALT, AST, total, and direct bilirubin were elevated. The prothrombin time result shows prolongation as well. Some of the liver biopsy results shown  13 can also be associated with Hepatitis B virus infection. However, considering the results of the hepatitis panel, the Hepatitis B surface antigen (HbsAg) and the Hepatitis B core antigen (HBcAg), which should strongly indicate Hepatitis B infection, were not active or detected. Thus, Hepatitis B infection must be ruled out in this case. ISCHEMIC HEPATITIS Ischemic hepatitis (IH), also known as "hypoxic hepatitis" or "shock liver," is a clinical, biochemical, and histological syndrome characterized by a rapid, significant, and transient rise in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the setting of various pathological conditions that result in reduced oxygen delivery or utilization by the liver. Symptoms may include nausea, vomiting, jaundice, and liver may be tender and enlarged (Jackson, 2024). This condition is most observed in patients with heart failure (HF), circulatory or septic shock, and respiratory failure. This diminished perfusion can occur in various clinical settings such as severe hypotension, shock, cardiac arrest, or vascular conditions affecting hepatic blood flow (Ciobanu & Gherasim, 2018). The pathogenesis of ischemic hepatitis is complex and is thought to occur through a 'two- hit' mechanism. Initially, the liver, already vulnerable due to its high metabolic demands and susceptibility to ischemic injury, encounters systemic hypoperfusion and ischemia as the second hit. This sequence of events results in a pronounced but transient elevation in liver enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reflecting hepatocellular injury. In the first 24-48 hours, there is an unexpected and rapid rise in aspartate aminotransferase (AST) levels, shortly followed by an increase in alanine aminotransferase (ALT). The diagnostic values for these liver enzymes can range from 10 to 250 times the normal upper limit, though the actual diagnostic cut-off may vary. Another characteristic feature is a higher level of plasma AST compared to ALT. Additional liver tests abnormalities may occur in relation to ischemic hepatitis severity is the presence of elevated total and, more specifically, unconjugated bilirubin (Ciobanu & Gherasim, 2018). In addition, as stated by Wahed (2021), within a short time after significant liver dysfunction, PT is prolonged because the liver cannot make enough blood-clotting proteins. Consequently, it takes longer for the blood to clot.  14 Unlike viral hepatitis, which typically involves inflammatory processes in the liver triggered by viruses like hepatitis A, B, or C, ischemic hepatitis does not primarily involve inflammation. Instead, it primarily results in hepatocellular necrosis, death of liver cells due to inadequate oxygen and nutrients (Jackson, 2024). As the liver experiences acute injury due to a significant reduction in blood flow, the pathological changes observed in this condition can include hepatocellular necrosis, ballooning degeneration, fibrosis, and ascites, though these findings may vary in timing and severity. On liver biopsy, hepatocellular necrosis is typically characterized by cell death with loss of hepatocyte architecture, cell swelling, and the presence of cell debris. Ballooning degeneration also occurs due to cellular injury where hepatocytes swell from cytoplasmic edema. It is often a response to acute liver stress and is associated with liver injury from ischemia. Moreover, some result in fibrosis which develops as a response to ongoing liver injury and inflammation. Ascites, or the accumulation of fluid in the abdominal cavity, can also occur as a complication of ischemic hepatitis if it progresses to cirrhosis or severe liver dysfunction (Sharma & Nagalli, 2023). It is significant that all the previous information about ischemic hepatitis, the symptoms, laboratory results, and also the histopathological results show great similarities with the patient’s condition in this case. However, history of heart failure (HF), circulatory or septic shock, and respiratory failure were not noted in the patient's case. Thus, ischemic hepatitis must be ruled out in this case. ACETAMINOPHEN TOXICITY Acetaminophen is one of the most widely used over-the-counter analgesic and antipyretic medications. Although the exact mechanism of action of the drug remains unclear, it is historically categorized along with nonsteroidal anti-inflammatory drugs (NSAIDs) due to its inhibition of the cyclooxygenase (COX) pathways. It possesses analgesic and antipyretic properties similar to NSAIDs but lacks peripheral anti-inflammatory effects (Gerriets, et al., 2024). More than 100 products contain acetaminophen, which is also present in many combination prescription drugs. If several similar products are consumed at a time, a person may inadvertently take too much acetaminophen. Toxicity also may develop if multiple smaller doses are taken over  15 time. Thus, exceeding the recommended doses can lead to severe liver damage or even liver failure (O’Malley, 2022). Prompt medical attention is crucial in cases of overdose to prevent serious complications. As stated in the “Guidelines for the Management of Acetaminophen Overdose” (Bond, et al., n.d), the clinical course of acetaminophen overdose generally occurs in a 3-phase sequential pattern. The first phase begins shortly after ingestion of a potentially toxic overdose and lasts for 12 to 24 hours. The patient may manifest signs of gastrointestinal irritability, nausea, vomiting, anorexia, diaphoresis, and pallor. If toxicity continues or is to ensue, there is a latent phase in terms of clinical findings of up to 48 hours. This is now the second phase. Initial symptoms abate and the patient may feel better. However, hepatic enzymes, bilirubin, lactate, phosphate, and prothrombin time or INR values will progressively rise, with hepatic enzymes often rising to striking levels. Right upper quadrant pain may develop as the liver becomes enlarged and tender. Most patients do not progress beyond this phase, especially if given acetylcysteine treatment. The subsequent clinical course is characterized by a gradual return of liver enzyme tests to normal (Bond, et al., n.d). In the third phase, a few patients will develop serious hepatic necrosis. Signs and symptoms of this third phase of the clinical course depend on the severity of hepatic damage and usually occur from 3 to 5 days following ingestion. The peak AST and ALT occurs between 72 to 96 hours post ingestion. Symptoms may be limited to anorexia, nausea, general malaise, and abdominal pain in less severe cases or may progress to confusion, stupor, and sequelae of hepatic necrosis including jaundice, coagulation defects, hypoglycemia, and encephalopathy, as well as renal failure and cardiomyopathy. Death, if it occurs, is generally a result of complications associated with fulminant hepatic failure. Mortality rates in patients with toxic acetaminophen levels who do not receive antidotal therapy are in the range of 3% to 4%. In nonfatal cases, serial liver biopsies and liver enzyme tests have shown prompt resolution without significant residual functional or architectural alterations of the liver (Bond, et al., n.d). According to Sharma and Nagalli, (2023), complete blood count findings typically remain normal in early acetaminophen toxicity, but emphasis is placed on monitoring liver enzymes (AST,  16 ALT) and other markers of liver function instead. The liver enzymes such as ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are more commonly monitored to assess liver damage in acetaminophen overdose. Farrel (2024), stated that AST and ALT concentrations begin to rise within 24 hours after an acute ingestion and peak at about 72 hours. In severe overdose, transaminase elevation can be detected as early as 12-16 hours post-ingestion. Toxicity is defined as serum AST or ALT concentrations greater than 1000 IU/L. A rapid progression of transaminase values to 3000 IU/L or greater reflects severe hepatotoxicity. Bilirubin levels can also be elevated due to impaired liver function, which leads to decreased conjugation and clearance of bilirubin from the bloodstream. Furthermore, acetaminophen overdose primarily affects the liver and does not typically cause alterations in white blood cell counts or differential counts since it generally does lead to systemic inflammatory responses or significant bone marrow suppression that would affect the differential count. On the other hand, prothrombin time (PT) can be affected in acetaminophen toxicity, which impairs the liver’s ability to produce clotting factors, including prothrombin (Factor II). As a result, prothrombin time, which measures the time it takes for blood to clot, may become prolonged. This is due to decreased synthesis of clotting factors by the damaged liver cells (Sharma & Nagalli, 2023). Histopathological changes in the liver can indeed include parenchymal collapse and ballooning degeneration. Hepatocyte dropout also occurs due to cell death caused by toxic metabolites of acetaminophen. Sahoo & Hart (n.d.). Liver biopsy results with severe hepatotoxicity also show hepatic centrilobular necrosis according to Farrel, (2024). Inflammatory response in the liver triggered by acetaminophen toxicity involves immune cells such as Kupffer cells and leukocytes. Fibrosis develops as a consequence of chronic liver injury, inflammation, oxidative stress, and dysregulated repair processes. Acetaminophen overdose can be effectively managed by focusing on a few basic principles. As in all cases of poisoning, healthcare providers should obtain a careful history and should have a high index of suspicion. When acetaminophen overdose is a possibility, an acetaminophen level should be obtained, and antidotal therapy should be initiated. When  17 acetylcysteine is administered soon after an overdose occurs, morbidity is significantly reduced and mortality virtually eliminated. The prognosis for patients with acetaminophen overdose is excellent, provided treatment is given expeditiously and appropriately (Bond, et al., n.d). Moreover, according to the Guidelines from the American Association for the Study of Liver Diseases (AASLD) recommend gastric lavage and administration of activated charcoal (AC) for all patients presenting within 4 hours of ingestion. It is remarkable that the patient in this case is experiencing severe abdominal pain, nausea, and vomiting for the past 24 hours. The patient also reported a recent flu-like illness, and jaundice with scleral icterus was seen upon examination. An abdominal palpation also revealed tenderness in the right upper quadrant. The patient had been experiencing persistent headaches over the past weeks and had been self-medicating with painkillers such as Tylenol, Panadol, and Ibuprofen taking up to 4 grams daily. AST, ALT, and Bilirubin were highly elevated and prolonged prothrombin time was shown. Liver failure and multi-organ dysfunction occurred which resulted in the patient’s death. The liver biopsy showed hepatocellular necrosis, parenchymal collapse with hepatocyte dropout and ballooning degeneration. Early fibrosis was also noted and there is mild to moderate increase of Kupffer cells seen in immunohistochemistry results. Correlating all the previous given information to the patient’s history, signs, symptoms and clinical findings, the combined evidence supports a definitive diagnosis of Acetaminophen Toxicity.  18 IV. CONCLUSION Upon the analysis of the study, the researchers came up with a list of potential diagnoses in correlation between the presented laboratory test results and clinical manifestations, such as Hepatitis B, Ischemic Hepatitis, and Acetaminophen Toxicity. Drawing from the evidence presented, which encompasses factors such as the impact of various influences, including the clinical manifestations, the patient history, and the laboratory findings, and a liver biopsy. Exceeding the maximum amount of dosage and the consumption of multiple drugs containing acetaminophen plays a vital role in the diagnostic process of Acetaminophen Toxicity. The cumulative evidence substantiates the conclusive diagnosis of Acetaminophen Toxicity.  19 V. ACKNOWLEDGEMENT This study’s successful completion was made possible through the invaluable guidance and support of several individuals who generously contributed their assistance throughout its preparation and completion of the study. We are deeply honored to extend our heartfelt gratitude and appreciation to Mr. Erwin D. Mandac, our dedicated adviser. We are profoundly thankful for the wealth of wisdom and knowledge you imparted to each one of us, your unwavering support, and your patience in addressing our numerous questions. Your consistent guidance throughout the entire research process has been instrumental, and we hold the utmost respect and gratitude for your contributions. To Mariano Marcos Memorial Hospital and Medical Center, Department of Pathology and Laboratories, we would also like to express our sincere appreciation for your willingness to provide us with a platform for learning and growth, as well as your role in helping us discover our potential, is sincerely acknowledged. The environment you provided, which was both safe and motivating, allowed us to refine our skills and enhance our expertise. We are extremely grateful to the dedicated staff who graciously shared their generosity and experience, guiding us on our journey. The experiences we gained were simultaneously humbling and empowering, and they will remain etched in our memories. Thank you for not only accommodating us but also for becoming a second home to us. To our beloved family and friends, we want to express our deepest gratitude for being a constant source of inspiration and motivation. Your unwavering support and unconditional love propelled us forward, keeping us grounded and resolute in pursuit of our dreams. Lastly, we offer thanks to our Lord Most High for bestowing upon us the gift of life and the strength to persevere. Your boundless grace sustained us through each day and beyond. May your divine light continue to illuminate our path and serve as our guiding beacon.  20 VI. REFERENCES Anderson, L. A., Sinha, S., Durbin, K., Entringer, S., Stewart, J., & Thornton, P. (2024, July 7). Acetaminophen overdose. https://www.drugs.com/cg/acetaminophen-overdorse.html Bond, G. R., Caravati, E. M., Dart, R. C., Heard, K., Hoffman, R. S., Rumack, B. H., & Snodgrass, W. R. (n.d.). Guidelines for the Management of Acetaminophen Overdose. https://www.tylenolprofessional.com/sites/tylenol_hcp_us/files/acetamin ophen_overdose_treatment_info.pdf Ciobanu, A. O., & Gherasim, L. (2018). Ischemic hepatitis – Intercorrelated pathology. MAEDICA – a Journal of Clinical Medicine. https://doi.org/10.26574/maedica.2018.13.1.5 Farrel, S. E. (2024, February 2). Acetaminophen Toxicity. https://emedicine.medscape.com/article/820200-overview Guzman, L. V., & Vyas, M. (2024, July 26). Hepatitis B Virus. https://www.pathologyoutlines.com/topic/liverhepB.html Gerriets, V., Anderson, J., Patel, P., & Nappe, T. M. (2023, January 11). Acetaminophen. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/ books/NBK482369/ Jackson, W. (2024, May 2). Ischemic Hepatitis. https://www.msdmanuals.com/home/liver-and gallbladder-disorders/blood vessel-disorders-of-the-liver/ischemic-hepatitis. Mount Sinai Health System. (2024). Hepatitis B. https://www.mountsinai.org/health library/diseases-conditions/hepatitis-b O’Malley, G. F., & O’Malley, R. (2022, June). Acetaminophen Poisoning. https://www.msdmanuals.com/professional/injuriespoisoning/poisoning/a etaminophen-poisoning Pathkind Labs. (2023, October 13). Defending against hepatitis B: Causes, symptoms, prevention. https://www.pathkindlabs.com/blog/hepatitis-b-causes symptoms-prevention  21 Sahoo, S., & Hart, J. (n.d.). Histopathological features of L-asparaginase-induced liver disease. https://pubmed.ncbi.nlm.nih.gov/14523682/ Samji, N. S. (2023, July 7). Viral Hepatitis Workup. https://emedicine.medscape.com /article/775507-workup Sharma, A., & Nagalli, S. (2023, July 3). Chronic Liver Disease. https://www.ncbi.nlm.nih.gov/books/NBK554597/ U.S. Food and Drug Administration. (2022, June 9). Acetaminophen. https://www.fda.gov/drugs/information-drug-class/acetaminophen Wahed, A. (2021, January 27). Prothrombin time and what it reveals about liver function. https://www.medmastery.com/guides/liver-lab-clinical-guide/prothrombi n-time-and-what-it-reveals-about-liver-function