258x258pxThe diagnosis of<unk>  in an individual is based on multiple factors.<unk>  may be suspected from laboratory findings, physical exam, and patient history. Imaging is generally obtained to evaluate the liver. A liver biopsy will confirm the diagnosis; however, is generally not required. Imaging Ultrasound is routinely used in the evaluation of<unk> . It may show a small and shrunken liver in advanced disease. On ultrasound, there is increased echogenicity with irregular appearing areas. Other suggestive findings are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. An enlarged spleen, which normally measures less than 11–12 cm in adults, may suggest underlying portal hypertension. Ultrasound may also screen for hepatocellular carcinoma and portal hypertension. This is done by assessing flow in the hepatic vein. An increased portal vein pulsatility may be seen. However, this may be a sign of elevated right atrial pressure. Portal vein pulsatility are usually measured by an pulsatility indices (PI). A number above a certain values indicates<unk>  (see table below). +Pulsatility indices (PI) Index Calculation Cutoff Average-based (Max – Min) / Average 0.5 Max-relative (Max – Min) / Max 0.5–0.54 left<unk>  is also diagnosable through a variety of new elastography techniques. When a liver becomes<unk> rhotic it will generally become stiffer. Determining the stiffness through imaging can determine the location and severity of disease. Techniques include transient elastography, acoustic radiation force impulse imaging, supersonic shear imaging and magnetic resonance elastography. Transient elastography and magnetic resonance elastography can help identify the stage of fibrosis. Compared to a biopsy, elastography can sample a much larger area and is painless. It shows a reasonable correlation with the severity of<unk> . Other modalities have been introduced which are incorporated into ultrasonagraphy systems. These include 2-dimensional shear wave elastography and point shear wave elastography which uses acoustic radiation force impulse imaging. Rarely are diseases of the bile ducts, such as primary sclerosing cholangitis, causes of<unk> . Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) may aid in the diagnosis. Lab findings The best predictors of<unk>  are ascites, platelet count 3, spider angiomata, and a Bonacini<unk>  discriminant score greater than 7 (as the sum of scores for platelet count, ALT/AST ratio and INR as per table). +Bonacini score Score Platelet count x109 ALT/AST ratio INR 0 >340 >1.7 1.4 3 160–219 ALT. However, normal aminotransferase levels do not preclude<unk> . * Alkaline phosphatase – slightly elevated but less than 2–3 times the upper limit of normal. * Gamma-glutamyl transferase – correlates with AP levels. Typically much higher in chronic liver disease from alcohol. * Bilirubin levels are normal when compensated, but may elevate as<unk>  progresses. * Albumin levels fall as the synthetic function of the liver declines with worsening<unk>  since albumin is exclusively synthesized in the liver. * Prothrombin time increases, since the liver synthesizes clotting factors. * Globulins increase due to shunting of bacterial antigens away from the liver to lymphoid tissue. * Serum sodium levels fall(hyponatremia) due to inability to excrete free water resulting from high levels of ADH and aldosterone. * Leukopenia and neutropenia are due to splenomegaly with splenic margination. * Coagulation defects occur, as the liver produces most of the coagulation factors, thus coagulopathy correlates with worsening liver disease. * Glucagon is increased in<unk> . * Vasoactive intestinal peptide is increased as blood is shunted into the intestinal system because of portal hypertension. * Vasodilators are increased (such as nitric oxide and carbon monoxide) reducing afterload with compensatory increase in cardiac output, mixed venous oxygen saturation. * Renin is increased (as well as sodium retention in kidneys) secondary to a fall in systemic vascular resistance. FibroTest is a biomarker for fibrosis that may be used instead of a biopsy. Other laboratory studies performed in newly diagnosed<unk>  may include: * Serology for hepatitis viruses, autoantibodies (ANA, antismooth muscle, antimitochondria, anti-LKM) * Ferritin and transferrin saturation: markers of iron overload as in hemochromatosis, copper and ceruloplasmin: markers of copper overload as in Wilson's disease * Immunoglobulin levels (IgG, IgM, IgA) – these immunoglobins are nonspecific, but may help in distinguishing various causes. * Cholesterol and glucose * Alpha 1-antitrypsin Markers of inflammation and immune cell activation are typically elevated in<unk> rhotic patients, especially in the decompensated disease stage: * C-reactive protein (CRP) * Procalcitonin (PCT) * Presepsin * soluble CD14 * soluble CD163 * soluble CD206 (mannose receptor) * soluble TREM-1 A recent study identified15 microbial biomarkers from the gut microbiota. These could potentially be used to discriminate patients with liver<unk>  from healthy individuals. Pathology Micrograph showing<unk> , trichrome stainThe gold standard for diagnosis of<unk>  is a liver biopsy. This is usually carried out as a fine-needle approach, through the skin (percutaneous), or internal jugular vein (transjugular). Endoscopic ultrasound-guided liver biopsy (EUS), using the percutaneous or transjugular route, has become a good alternative to use. EUS can target liver areas that are widely separated, and can deliver bi-lobar biopsies. A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest<unk> . Furthermore, a small but significant risk of complications is associated with liver biopsy, and<unk>  itself predisposes for complications caused by liver biopsy. Once the biopsy is obtained, a pathologist will study the sample.<unk>  is defined by its features on microscopy: (1) the presence of regenerating nodules of hepatocytes and (2) the presence of fibrosis, or the deposition of connective tissue between these nodules. The pattern of fibrosis seen can depend on the underlying insult that led to<unk> . Fibrosis can also proliferate even if the underlying process that caused it has resolved or ceased. The fibrosis in<unk>  can lead to destruction of other normal tissues in the liver: including the sinusoids, the space of Disse, and other vascular structures, which leads to altered resistance to blood flow in the liver, and portal hypertension. File:Histopathology of mild zone 3 steatosis without fibrosis (van Gieson).No fibrosis, but mild zone 3 steatosis, in which collagen fibres (pink–red, arrow) are confined to portal tracts (P) (Van Gieson's stain) File:Histopathology of steatohepatitis with mild fibrosis in the form of fibrous expansion (van Gieson).Histopathology of steatohepatitis with mild fibrosis in the form of fibrous expansion (Van Gieson's stain) File:Histopathology of steatohepatitis with moderate fibrosis, with thin fibrous bridges (van Gieson).Histopathology of steatohepatitis with moderate fibrosis, with thin fibrous bridges (Van Gieson's stain) File:Histopathology of steatohepatitis with established<unk> , with thick bands of fibrosis (van Gieson).Histopathology of steatohepatitis with established<unk> , with thick bands of fibrosis (Van Gieson's stain) File:Cirrhosis of the liver (trichrome stain) (5690946257).Trichrome stain, showing<unk>  as a nodular texture surrounded by fibrosis (wherein collagen is stained blue). As<unk>  can be caused by many different entities which injure the liver in different ways, cause-specific abnormalities may be seen. For example, in chronic hepatitis B, there is infiltration of the liver parenchyma with lymphocytes. In congestive hepatopathy there are erythrocytes and a greater amount of fibrosis in the tissue surrounding the hepatic veins. In primary biliary cholangitis, there is fibrosis around the bile duct, the presence of granulomas and pooling of bile. Lastly in alcoholic<unk> , there is infiltration of the liver with neutrophils. Macroscopically, the liver is initially enlarged, but with the progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm, and if associated with steatosis the color is yellow. Depending on the size of the nodules, there are three macroscopic types: micronodular, macronodular, and mixed<unk> . In the micronodular form (Laennec's<unk>  or portal<unk> , regenerating nodules are under 3 mm. In macronodular<unk>  (post-necrotic<unk> , the nodules are larger than 3 mm. Mixed<unk>  consists of nodules of different sizes. File:Gross pathology of alcoholic liver<unk> .Micronodular<unk> , with diffuse areas of pallor. File:Wątroba marska (Ultima Thule).Pale macronodules of<unk> . File:Hepatocellular carcinoma 1.Cirrhosis leading to hepatocellular carcinoma (autopsy specimen)
Cirrhosis
Terry's nails
Hepatitis
Nephrotic syndrome  Nephrotic syndrome  1
Fatty liver disease
Alcoholic liver disease
Non-alcoholic fatty liver disease
Chronic liver disease