Differential Diagnosis

The patient presents with elevated total and direct bilirubin, along with increased liver enzymes (AST, ALT, ALP), and mild hepatosplenomegaly on CT abdomen. The negative autoimmune markers (ANA, LKM1, SMA) help to narrow down the differential diagnoses. Here's a categorized approach to the differential diagnosis:

• Single Most Likely Diagnosis
  • Cholestasis due to Drug-Induced Liver Injury (DILI): Given the elevated direct bilirubin and liver enzymes without significant autoimmune markers, DILI is a strong consideration. Many drugs can cause cholestasis, and the presentation can vary widely.
• Other Likely Diagnoses
  • Viral Hepatitis: Although not explicitly mentioned, viral hepatitis (e.g., hepatitis B or C) could present with similar lab findings. The absence of autoimmune markers does not rule out viral causes.
  • Alcoholic Liver Disease: With elevated AST:ALT ratio, alcoholic liver disease could be considered, especially if the patient has a history of alcohol use.
  • Non-Alcoholic Fatty Liver Disease (NAFLD): Given the mild hepatosplenomegaly and elevated liver enzymes, NAFLD is a possibility, particularly in the context of metabolic syndrome or obesity.
• Do Not Miss Diagnoses
  • Budd-Chiari Syndrome: Although less likely, this condition (hepatic vein thrombosis) can present with hepatosplenomegaly and abnormal liver function tests. It's critical to consider due to its potential for severe complications if not treated promptly.
  • Wilson's Disease: An inherited disorder of copper metabolism, Wilson's disease can cause liver dysfunction and might not always present with typical Kayser-Fleischer rings or neuropsychiatric symptoms early on.
• Rare Diagnoses
  • Primary Biliary Cholangitis (PBC): Now known as primary biliary cholangitis, this autoimmune disease of the liver could be considered, despite negative autoimmune markers, as these can sometimes be negative in early disease.
  • Primary Sclerosing Cholangitis (PSC): A chronic liver disease characterized by inflammation and fibrosis of the bile ducts, PSC is less common and might not always have positive autoimmune markers.
  • Hemochromatosis: A genetic disorder leading to excessive iron accumulation in the body, hemochromatosis can cause liver dysfunction and might be considered in the differential, especially if other signs of iron overload are present.

Each of these diagnoses requires careful consideration of the patient's history, physical examination, and additional diagnostic tests as needed to determine the underlying cause of the liver dysfunction.