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.

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.

Although most patients present without any known risk factors evident, a number of risk factors for the development of cholangiocarcinoma have been described. In the Western world, the most common of these is primary sclerosing cholangitis (PSC), an inflammatory disease of the bile ducts which is closely associated with ulcerative colitis (UC). Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is on the order of 10%–15%, although autopsy series have found rates as high as 30% in this population.

Certain parasitic liver diseases may be risk factors as well. Colonization with the liver flukes "Opisthorchis viverrini" (found in Thailand, Laos PDR, and Vietnam) or "Clonorchis sinensis" (found in China, Taiwan, eastern Russia, Korea, and Vietnam) has been associated with the development of cholangiocarcinoma. Patients with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or hepatitis C), alcoholic liver disease, or cirrhosis of the liver due to other causes, are at significantly increased risk of cholangiocarcinoma. HIV infection was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether HIV itself or other correlated and confounding factors (e.g. hepatitis C infection) were responsible for the association.

Infection with the bacteria "Helicobacter bilis" and "Helicobacter hepaticus" species can cause biliary cancer.

Congenital liver abnormalities, such as Caroli's syndrome (a specific type of five recognized choledochal cysts), have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma. The rare inherited disorders Lynch syndrome II and biliary papillomatosis have also been found to be associated with cholangiocarcinoma. The presence of gallstones (cholelithiasis) is not clearly associated with cholangiocarcinoma. However, intrahepatic stones (called hepatolithiasis), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma. Exposure to Thorotrast, a form of thorium dioxide which was used as a radiologic contrast medium, has been linked to the development of cholangiocarcinoma as late as 30–40 years after exposure; Thorotrast was banned in the United States in the 1950s due to its carcinogenicity.

In addition to virus-related cirrhosis described above, other causes of cirrhosis can lead to HCC. Alcohol intake correlates with risk of HCC, and the risk is far greater in individuals with an alcohol-induced cirrhotic liver. There are a few disorders that are known to cause cirrhosis and lead to cancer, including hereditary hemochromatosis and primary biliary cirrhosis.

The most common physical indications of cholangiocarcinoma are abnormal liver function tests, jaundice (yellowing of the eyes and skin occurring when bile ducts are blocked by tumor), abdominal pain (30%–50%), generalized itching (66%), weight loss (30%–50%), fever (up to 20%), and changes in the color of stool or urine. To some extent, the symptoms depend upon the location of the tumor: patients with cholangiocarcinoma in the extrahepatic bile ducts (outside the liver) are more likely to have jaundice, while those with tumors of the bile ducts within the liver more often have pain without jaundice.

Blood tests of liver function in patients with cholangiocarcinoma often reveal a so-called "obstructive picture," with elevated bilirubin, alkaline phosphatase, and gamma glutamyl transferase levels, and relatively normal transaminase levels. Such laboratory findings suggest obstruction of the bile ducts, rather than inflammation or infection of the liver parenchyma, as the primary cause of the jaundice.

Aflatoxin exposure can lead to the development of HCC. The aflatoxins are a group of chemicals produced by the fungi "Aspergillus flavus" (the name comes from "A. flavus" toxin) and "A. parasiticus". Food contamination by the fungi leads to ingestion of the chemicals, which are very toxic to the liver. Common foodstuffs contaminated with the toxins are cereals, peanuts and other vegetables. Contamination of food is common in Africa, South-East Asia and China. Concurrent HBV infection and aflatoxin exposure increases the risk of liver cancer to over three times that seen in HBV infected individuals without aflatoxin exposure. The mechanism by which aflatoxins cause cancer is through genetic mutation of a gene required for the prevention of cancer: p53.

The disease is typically progressive, leading to fulminant liver failure and death in childhood, in the absence of liver transplantation. Hepatocellular carcinoma may develop in PFIC-2 at a very early age; even toddlers have been affected.

There is a 2-3:1 male-to-female predilection in primary sclerosing cholangitis. PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of inflammatory bowel disease (IBD). PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences. There is relatively little data on the prevalence and incidence of primary sclerosing cholangitis, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, it is likely that the risk is higher in populations where UC is more common. In the United States, an estimated 29,000 individuals have PSC.

The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population. Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.

PSC is strongly associated with inflammatory bowel disease (IBD), in particular ulcerative colitis (UC) and to a lesser extent Crohn's disease. As many as 5% of patients with IBD are co-diagnosed with PSC and approximately 70% of people with PSC have IBD. Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital.

Various forms of gallbladder disease such as gallstones and gallbladder polyps are also common in those with PSC. Approximately 25% of people with PSC have gallstones. Ultrasound surveillance of the gallbladder every year is recommended for people with PSC. Any person with PSC who is found to have a mass in the gallbladder should undergo surgical removal of the gallbladder due to the high risk of cholangiocarcinoma. Osteoporosis (hepatic osteodystrophy) and hypothyroidism are also associated with PSC.

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.

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).

Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years.

Possible causes:

- pregnancy

- androgens

- birth control pills

- antibiotics (such as TMP/SMX)

- abdominal mass (e.g. cancer)

- biliary atresia and other pediatric liver diseases

- biliary trauma

- congenital anomalies of the biliary tract

- gallstones

- acute hepatitis

- cystic fibrosis

- intrahepatic cholestasis of pregnancy (obstetric cholestasis)

- primary biliary cirrhosis, an autoimmune disorder

- primary sclerosing cholangitis, associated with inflammatory bowel disease

- some drugs (e.g. flucloxacillin and erythromycin)

Drugs such as gold salts, nitrofurantoin, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, cimetidine, erythromycin, estrogen, and statins can cause cholestasis and may result in damage to the liver.

Caroli disease is typically found in Asia, and diagnosed in persons under the age of 22. Cases have also been found in infants and adults. As medical imaging technology improves, diagnostic age decreases.

Liver tumors or hepatic tumors are tumors or growths on or in the liver (medical terms pertaining to the liver often start in "hepato-" or "hepatic" from the Greek word for liver, "hepar"). Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant (cancerous). They may be discovered on medical imaging (even for a different reason than the cancer itself), or may be present in patients as an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction.

Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications.

Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.

Liver disease can occur through several mechanisms. A common form of liver disease is viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012 NICE publication, "about 85% of hepatitis B infections in newborns become chronic". In occult cases, Hepatitis B virus is present by HBV DNA, but testing for HBsAg is negative. High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. In the earlier stages of alcoholic liver disease, fat builds up in the liver's cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease. Approximately 3–10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma.

According to Tilg, et al., gut microbiome could very well have an effect, be involved in the pathophysiology, on the various types of liver disease which an individual may encounter.

There are more than a hundred different kinds of liver disease. Symptoms may include jaundice and weight loss. These are some of the most common:

- Fascioliasis, a parasitic infection of liver caused by a Liver fluke of the "Fasciola" genus, mostly the "Fasciola hepatica".

- Hepatitis, inflammation of the liver, is caused by various viruses (viral hepatitis) also by some liver toxins (e.g. alcoholic hepatitis), autoimmunity (autoimmune hepatitis) or hereditary conditions.

- Alcoholic liver disease is a hepatic manifestation of alcohol overconsumption, including fatty liver disease, alcoholic hepatitis, and cirrhosis. Analogous terms such as "drug-induced" or "toxic" liver disease are also used to refer to disorders caused by various drugs.

- Fatty liver disease (hepatic steatosis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells. Non-alcoholic fatty liver disease is a spectrum of disease associated with obesity and metabolic syndrome.

- Hereditary diseases that cause damage to the liver include hemochromatosis, involving accumulation of iron in the body, and Wilson's disease. Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency and glycogen storage disease type II.

- In transthyretin-related hereditary amyloidosis, the liver produces a mutated transthyretin protein which has severe neurodegenerative and/or cardiopathic effects. Liver transplantation can give a curative treatment option.

- Gilbert's syndrome, a genetic disorder of bilirubin metabolism found in a small percent of the population, can cause mild jaundice.

- Cirrhosis is the formation of fibrous tissue (fibrosis) in the place of liver cells that have died due to a variety of causes, including viral hepatitis, alcohol overconsumption, and other forms of liver toxicity. Cirrhosis causes chronic liver failure.

- Primary liver cancer most commonly manifests as hepatocellular carcinoma and/or cholangiocarcinoma; rarer forms include angiosarcoma and hemangiosarcoma of the liver. (Many liver malignancies are secondary lesions that have metastasized from primary cancers in the gastrointestinal tract and other organs, such as the kidneys, lungs.)

- Primary biliary cirrhosis is a serious autoimmune disease of the bile capillaries.

- Primary sclerosing cholangitis is a serious chronic inflammatory disease of the bile duct, which is believed to be autoimmune in origin.

- Budd–Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein.

There are several types of benign liver tumor.

Hemangiomas: These are the most common type of benign liver tumor, found in up to 7% of autopsy specimens. They start in blood vessels. Most of these tumors do not cause symptoms and do not need treatment. Some may bleed and need to be removed if it is mild to severe. A rare tumor is Infantile hemangioendothelioma.

Hepatic adenomas: These benign epithelial liver tumors develop in the liver and are also an uncommon occurrence, found mainly in women using estrogens as contraceptives, or in cases of steroid abuse. They are, in most cases, located in the right hepatic lobe and are frequently seen as solitary. The size of adenomas range from 1 to 30 cm. Symptoms associated with hepatic adenomas are all associate with large lesions which can cause intense abdominal pain. Over the last few decades there has been an increase with occurrences of this specific type of adenoma. The prognosis for these tumors has still not been mastered. Some correlations have been made such as malignant transformation, spontaneous hemorrhage, and rupture.

Focal nodular hyperplasia (FNH) is the second most common tumor of the liver. This tumor is the result of a congenital arteriovenous malformation hepatocyte response. This process is one in which all normal constituents of the liver are present, but the pattern by which they are presented is abnormal. Even though those conditions exist the liver still seems to perform in the normal range. Other types include nodular regenerative hyperplasia and hamartoma.

Recurrent pyogenic cholangitis is characterised by recurrent bouts of bacterial cholangitis with primary hepatolithiasis. It is prevalent in Hong Kong and East Asian including China, Taiwan, Korea, Japan, Indonesia and the Philippines. Apart from affecting humans it is also a common disease in cats.

Suppurative cholangitis, liver abscess, empyema of the gallbladder, acute pancreatitis, thrombophlebitis of hepatic or portal veins, and septicemia are acute complications of the disease, to which patients may succumb during the acute attacks.

Chronically, complications include cholangiocarcinoma and intraductal papillary neoplasm.

Diet and lifestyle are believed to play a large role in whether colorectal polyps form. Studies show there to be a protective link between consumption of cooked green vegetables, brown rice, legumes, and dried fruit and decreased incidence of colorectal polyps.

A portosystemic shunt (PSS), also known as a liver shunt, is a bypass of the liver by the body's circulatory system. It can be either a congenital (present at birth) or acquired condition.

Congenital PSS is a hereditary condition in dogs and cats, its frequency varying depending on the breed. The shunts found mainly in small dog breeds such as Shih Tzus, Tibetan Spaniels, Miniature Schnauzers and Yorkshire Terriers, and in cats such as Persians, British Shorthairs, Himalayans, and mixed breeds are usually extrahepatic (outside the liver), while the shunts found in large dog breeds such as Irish Wolfhounds and Labrador Retrievers tend to be intrahepatic (inside the liver).

Acquired PSS is uncommon and is found in dogs and cats with liver disease such as cirrhosis causing portal hypertension, which is high blood pressure in the portal vein.

Acute fatty liver of pregnancy is a rare condition and occurs in approximately one in 7,000 to one in 15,000 pregnancies. The mortality from acute fatty liver of pregnancy has been reduced significantly to 18%, and is now related primarily to complications, particularly DIC (Disseminated Intravascular Coagulation) and infections. After delivery, most mothers do well, as the stimulus for fatty acid overload is removed. The disease can recur in future pregnancies, with a calculated genetic chance of 25%; the actual rate is lower, however. Mortality of the foetus has also diminished significantly, but still remains 23%, and may be related to the need for premature delivery.