Upon discovery of a liver tumor, the main issue in the workup is to determine whether the tumor is benign or malignant. Many imaging modalities are used to aid in the diagnosis of malignant liver tumors. For the most common of these, hepatocellular carcinoma (HCC), these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.

Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders..

Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.

Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders.

Ultrasonography of liver tumors involves two stages: detection and characterization. Tumor detection is based on the performance of the method and should include morphometric information (three axes dimensions, volume) and topographic information (number, location specifying liver segment and lobe/lobes). The specification of these data is important for staging liver tumors and prognosis. Tumor characterization is a complex process based on a sum of criteria leading towards tumor nature definition. Often, other diagnostic procedures, especially interventional ones are no longer necessary. Tumor characterization using the ultrasound method will be based on the following elements: consistency (solid, liquid, mixed), echogenicity, structure appearance (homogeneous or heterogeneous), delineation from adjacent liver parenchyma (capsular, imprecise), elasticity, posterior acoustic enhancement effect, the relation with neighboring organs or structures (displacement, invasion), vasculature (presence and characteristics on Doppler ultrasonography and contrast-enhanced ultrasound (CEUS).

There are no specific blood tests that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of cholangiocarcinoma.

Ultrasound of the liver and biliary tree is often used as the initial imaging modality in patients with suspected obstructive jaundice. Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma. Computed tomography (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.

The most common method of testing for hepatoblastoma is a blood test checking the alpha-fetoprotein level. Alpha-fetoprotein (AFP) is used as a biomarker to help determine the presence of liver cancer in children. At birth, infants have relatively high levels of AFP, which fall to normal adult levels by the first year of life. The normal level for AFP in children has been reported as lower than 50 nanograms per milliliter (ng/ml) and 10 ng/ml. An AFP level greater than 500 (ng/ml) is a significant indicator of hepatoblastoma. AFP is also used as an indicator of treatment success. If treatments are successful in removing the cancer, the AFP level is expected to return to normal.

Prevention of cancers can be separated into primary, secondary, and tertiary prevention. Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination against the hepatitis C virus is currently unavailable. Other forms of primary prevention are aimed at limiting transmission of these viruses by promoting safe injection practices, screening blood donation products, and screening high-risk asymptomatic individuals. Aflatoxin exposure can be avoided by post-harvest intervention to discourage mold, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.

Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible. Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.

Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs and antiviral drugs.

Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas. Other liver findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. An enlarged spleen (splenomegaly), which normally measures less than 11–12 cm in adults, is suggestive of cirrhosis with portal hypertension, in the right clinical context. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension, and Budd-Chiari syndrome (by assessing flow in the hepatic vein).

Cirrhosis is diagnosed with a variety of elastography techniques. Because a cirrhotic liver is generally stiffer than a healthy one, imaging the liver's stiffness can give diagnostic information about the location and severity of cirrhosis. Techniques used include transient elastography, acoustic radiation force impulse imaging, supersonic shear imaging and magnetic resonance elastography. Compared to a biopsy, elastography can sample a much larger area and is painless. It shows a reasonable correlation with the severity of cirrhosis.

Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI (MRCP).

Blood tests should be done, importantly liver-function series, which will give a good impression of the patient's broad metabolic picture.

A complete blood test can help distinguish intrinsic liver disease from extrahepatic bile-duct obstruction. An ultrasound of the liver can reliably detect a dilated biliary-duct system,

it can also detect the characteristics of a cirrhotic liver.Computerized tomography (CT) can help to obtain accurate anatomical information, in individuals with hepatomegaly.

A number of liver function tests (LFTs) are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins, serum albumin, serum globulin,

alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time.

Imaging tests such as transient elastography, ultrasound and magnetic resonance imaging can be used to examine the liver tissue and the bile ducts. Liver biopsy can be performed to examine liver tissue to distinguish between various conditions; tests such as elastography may reduce the need for biopsy in some situations.

Gastroscopy (endoscopic examination of the esophagus, stomach, and duodenum) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. If these are found, prophylactic local therapy may be applied (sclerotherapy or banding) and beta blocker treatment may be commenced.

Rarely are diseases of the bile ducts, such as primary sclerosing cholangitis, causes of cirrhosis. Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) may aid in the diagnosis.

Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:

- By using steroid-based drugs in autoimmune hepatitis.

- Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis.

- Wilson’s disease, a condition where copper builds up in the body, can be managed with drugs which bind copper allowing it to be passed from your body in urine.

- In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid (URSO, also referred to as UDCA) may be given.

Surgical removal of the tumor, adjuvant chemotherapy prior to tumor removal, and liver transplantation have been used to treat these cancers. Primary liver transplantation provides high, long term, disease-free survival rate in the range of 80%, in cases of complete tumor removal and adjuvant chemotherapy survival rates approach 100%. The presence of metastases is the strongest predictor of a poor prognosis.

Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. This is variable as, due to obstruction, jaundice may present early and compel the patient to seek help. Complete resection of the tumor offers hope of long-term survival, and of late there has been renewed interest in liver transplantation from deceased donors along with add on therapy. Prognosis remains poor.

Approximately 15,000 new cases of liver and biliary tract carcinoma are diagnosed annually in the United States, with roughly 10% of these cases being Klatskin tumors. Cholangiocarcinoma accounts for approximately 2% of all cancer diagnoses, with an overall incidence of 1.2/100,000 individuals. Two-thirds of cases occur in patients over the age of 65, with a near ten-fold increase in patients over 80 years of age. The incidence is similar in both men and women.

Intraductal papillary mucinous neoplasms can come to clinical attention in a variety of different ways. The most common symptoms include abdominal pain, nausea and vomiting. The most common signs patients have when they come to medical attention include jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), weight loss, and acute pancreatitis. These signs and symptoms are not specific for an intraductal papillary mucinous neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have an intraductal papillary mucinous neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal dilatation of the pancreatic duct or one of the branches of the pancreatic duct. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

IPMN forms cysts (small cavities or spaces) in the pancreas. These cysts are visible in CT scans (X-ray computed tomography). However, many pancreatic cysts are benign (see Pancreatic disease).

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (i.e. undergoing an ultrasound, CT or MRI scan) for another reason. Up to 6% of patients undergoing pancreatic resection did so for treatment of incidental IPMNs.

In 2011, scientists at Johns Hopkins reported that they have developed a gene-based test that can be used to distinguish harmless from precancerous pancreatic cysts. The test may eventually help patients with harmless cysts avoid needless surgery. Bert Vogelstein and his colleagues discovered that almost all of the precancerous cysts (intraductal papillary mucinous neoplasms) of the pancreas have mutations in the KRAS and/or the GNAS gene. The researchers then tested a total of 132 intraductal papillary mucinous neoplasms for mutations in KRAS and GNAS. Nearly all (127) had mutations in GNAS, KRAS or both. Next, the investigators tested harmless cysts such as serous cystadenomas, and the harmless cysts did not have GNAS or KRAS mutations. Larger numbers of patients must be studied before the gene-based test can be widely offered.

On microscopic examination of liver biopsy specimens, PBC is characterized by interlobular bile duct destruction. These histopathologic findings in primary biliary cholangitis include the following:

- Inflammation of the bile ducts, characterized by intraepithelial lymphocytes, and

- Periductal epithelioid granulomata.

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Chronic liver diseases like chronic hepatitis, chronic alcohol abuse or chronic toxic liver disease may cause

- liver failure and hepatorenal syndrome

- fibrosis and cirrhosis of liver

Cirrhosis may also occur in primary biliary cirrhosis. Rarely, cirrhosis is congenital.

This remains a challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. Several clinical scales such as CIOMS/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. CIOMS/RUCAM scale involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), “probable” (score 6-8), “possible” (score 3-5), “unlikely” (score 1-2) and “excluded” (score ≤ 0). In clinical practice, physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in amoxycillin-clauvonic acid ).

Treatment of hepatomegaly will vary depending on the cause of the liver enlargement and hence accurate diagnosis is the primary concern. In the case of auto-immune liver disease, prednisone and azathioprine may be used for treatment.

In the case of lymphoma the treatment options include single-agent (or multi-agent) chemotherapy and regional radiotherapy, also surgery may be an option in specific situations.Meningococcal group C conjugate vaccine are also used in some cases.

In primary biliary cirrhosis ursodeoxycholic acid helps the bloodstream remove bile which may increase survival in some affected individuals.

Biochemical markers include a normal GGT for PFIC-1 and -2, with a markedly elevated GGT for PFIC-3. Serum bile acid levels are grossly elevated. Serum cholesterol levels are typically not elevated, as is seen usually in cholestasis, as the pathology is due to a transporter as opposed to an anatomical problem with biliary cells.

Serous cystic neoplasms can come to clinical attention in a variety of ways. The most common symptoms are very non-specific and include abdominal pain, nausea and vomiting. In contrast to many of the other tumors of the pancreas, patients rarely develop jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), or weight loss. These signs and symptoms are not specific for a serous cystic neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have serous cystic neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal a cystic mass within the pancreas. The cysts do not communicate with the larger pancreatic ducts. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason.

Malignant neoplasm of liver and intrahepatic bile ducts. The most frequent forms are metastatic malignant neoplasm of liver)

- liver cell carcinoma

- hepatocellular carcinoma

- hepatoma

- cholangiocarcinoma

- hepatoblastoma

- angiosarcoma of liver

- Kupffer cell sarcoma

- other sarcomas of liver

Benign neoplasm of liver include hepatic hemangiomas, hepatic adenomas, and focal nodular hyperplasia (FNH).

To diagnose PBC, it needs to be distinguished from other conditions with similar symptoms, such as autoimmune hepatitis or primary sclerosing cholangitis (PSC).

- Abnormalities in liver enzyme tests are usually present and elevated gamma-glutamyl transferase and alkaline phosphatase (ALP) are found in early disease. Elevations in bilirubin occur in advanced disease.

- Antimitochondrial antibodies are the characteristic serological marker for PBC, being found in 90%-95% of patients and only 1% of controls. PBC patients have AMA against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria. Those people who are AMA negative but with disease similar to PBC have been found to have AMAs when more sensitive detection methods are employed.

- Other auto-antibodies may be present:

- Abdominal ultrasound, MR scanning (MRCP) or a CT scan is usually performed to rule out blockage to the bile ducts. This may be needed if a condition causing secondary biliary cirrhosis, such as other biliary duct disease or gallstones, needs to be excluded. A liver biopsy may help, and if uncertainty remains as in some patients, an endoscopic retrograde cholangiopancreatography (ERCP), an endoscopic investigation of the bile duct, may be performed.

Most patients can be diagnosed without invasive investigation, as the combination of anti-mitochondrial antibodies and typical (cholestatic) liver enzyme tests are considered diagnostic. However, a liver biopsy is needed to determine the stage of disease.