effect as fat molecules accumulate and are broken down in the setting of an oxidative stress response. Over time, this abnormal lipid deposition triggers the immune system via toll-like receptor 4 (TLR4) resulting in the production of inflammatory cytokines such as TNF that cause liver cell injury and death. These events mark the transition to steatohepatitis and in the setting of chronic injury, fibrosis eventually develops setting up events that lead to cirrhosis and hepatocellular carcinoma. Microscopically, changes that can be seen include steatosis with large and swollen hepatocytes (ballooning), evidence of cellular injury and cell death (apoptosis, necrosis), evidence of inflammation in particular in zone 3 of the liver, variable degrees of fibrosis and Mallory bodies. Diagnosis Diagnosis of hepatitis is made on the basis of some or all of the following: a person's signs and symptoms, medical history including sexual and substance use history, blood tests, imaging, and liver biopsy. In general, for viral hepatitis and other acute causes of hepatitis, the person's blood tests and clinical picture are sufficient for diagnosis. For other causes of hepatitis, especially chronic causes, blood tests may not be useful. In this case, liver biopsy is the gold standard for establishing the diagnosis: histopathologic analysis is able to reveal the precise extent and pattern of inflammation and fibrosis. Biopsy is typically not the initial diagnostic test because it is invasive and is associated with a small but significant risk of bleeding that is increased in people with liver injury and cirrhosis. Blood testing includes liver enzymes, serology (i.e. for autoantibodies), nucleic acid testing (i.e. for hepatitis virus DNA/RNA), blood chemistry, and complete blood count. Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis. Generally, AST and ALT are elevated in most cases of hepatitis regardless of whether the person shows any symptoms. The degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis. Ultrasound, CT, and MRI can all identify steatosis (fatty changes) of the liver tissue and nodularity of the liver surface suggestive of cirrhosis. CT and especially MRI are able to provide a higher level of detail, allowing visualization and characterize such structures as vessels and tumors within the liver. Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation