Liver cancer

Source: Wikipedia, the free encyclopedia.
Liver cancer
Other namesHepatic cancer, primary hepatic malignancy, primary liver cancer
Five-year survival rates ~18% (US);[2] 40% (Japan)[5]
Frequency618,700 (point in time in 2015)[6]
Deaths782,000 (2018)[7]

Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is

liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers.[3] Instances of liver cancer are increasing globally.[8][9]

Primary liver cancer is globally the sixth-most frequent cancer and the fourth-leading cause of death from cancer.[7][10] In 2018, it occurred in 841,000 people and resulted in 782,000 deaths globally.[7] Higher rates of liver cancer occur where hepatitis B and C are common, including Asia and sub-Saharan Africa.[3] Males are more often affected with hepatocellular carcinoma (HCC) than females.[3] Diagnosis is most frequent among those 55 to 65 years old.[2]

The leading cause of liver cancer is

tissue biopsy.[1]

Given that there are many different causes of liver cancer, there are many approaches to liver cancer prevention. These efforts include immunization against hepatitis B,[3] hepatitis B treatment, hepatitis C treatment, decreasing alcohol use,[8] decreasing exposure to aflatoxin in agriculture, and management of obesity and diabetes.[9] Screening is recommended in those with chronic liver disease.[3] For example, it is recommended that people with chronic liver disease who are at risk for hepatocellular carcinoma be screened every 6 months using ultrasound imaging.[8]

Because liver cancer is an

itching, weight loss and fever.[12]

Treatment options may include

embolization therapy or liver transplantation may be used.[1]

Classification

Liver cancer can come from the liver

immune cells[13]
There are many sub-types of liver cancer, the most common of which are described below.

Hepatocellular carcinoma

Main article: Hepatocellular carcinoma
Liver tumor types by relative incidence in adults in the United States (liver cancers in dark red color).[14]

The most frequent liver cancer, accounting for approximately 75% of all primary liver cancers, is hepatocellular carcinoma (HCC).[15] HCC is a cancer formed by liver cells, known as hepatocytes, that become malignant. In terms of cancer deaths, worldwide HCC is considered the 3rd most common cause of cancer mortalities.[16]

In terms of HCC diagnosis, it is recommended that people with risk factors (including known chronic liver disease, cirrhosis, etc.) should receive screening ultrasounds. If the ultrasound shows a focal area that is larger than 1 centimeter in size, patients should then get a triple-phase contrast-enhanced CT or MRI scan.[17] HCC can then be diagnosed radiologically using the Liver Imaging Reporting and Data System (LI-RADS).[18] There is also a variant type of HCC that consists of both HCC and cholangiocarcinoma.[19]

Intrahepatic cholangiocarcinoma

Main article:
Intrahepatic cholangiocarcinoma

Cancer of the bile duct (

CA-125.[21]

Angiosarcoma and hemangiosarcoma

Main article: Liver angiosarcoma

These are rare and aggressive liver cancers, yet are the third most common primary liver cancer making up 0.1-2.0% of primary liver cancer.

bleeding or hemorrhage and subsequent dying of tissue (necrosis)).[23] Biopsy with histopathological evaluation yields the definitive diagnosis.[22] While the cause is often never identified (75% are idiopathic), they are associated with exposures to substances such as vinyl chloride, arsenic, thorotrast (e.g. occupational exposure). Radiation is also a risk factor.[22] In adults, these tumors are more common in males; however, in children they are more common in females.[22]

Even with surgery prognosis is poor with most individuals not living longer than six months after diagnosis. Only 3% of individuals live longer than two years.[22]

Hepatoblastoma

Main article: Hepatoblastoma

Another type of cancer formed by liver cells is hepatoblastoma, which is specifically formed by immature liver cells.[20] It is a rare malignant tumor that primarily develops in children, and accounts for approximately 1% of all cancers in children and 79% of all primary liver cancers under the age of 15.[24][25] Most hepatoblastomas form in the right lobe.[26]

Metastasis to liver

Many cancers found in the liver are not true liver cancers but are cancers from other sites in the body that have spread to the liver (known as

renal cancer, prostate cancer
.

Children

The Children's Oncology Group (COG) has developed a protocol to help diagnose and manage childhood liver tumors.[27]

Causes

Viral infection

electron micrograph shows hepatitis B
virus "Dane particles", or virions.

Viral infection with hepatitis C virus (HCV) or Hepatitis B virus (HBV) is the chief cause of liver cancer in the world today, accounting for 80% of HCC.[28][29][30] Men with chronic HCV or HBV are more likely to develop HCC than women with chronic HCV or HBV; however, the reasons for this gender difference is unknown. HBV infection is also linked to cholangiocarcinoma.[31] The role of viruses other than HCV or HBV in liver cancer is much less clear, even though there is some evidence that co-infection of HBV and hepatitis D virus may increase the risk for HCC.[32]

HBV and HCV can lead to HCC, because these viral infections cause massive

signal transduction pathways. By doing this, the viruses can prevent cells from undergoing a programmed form of cell death (apoptosis) and promote viral replication and persistence.[28][34]

HBV and HCV also induce malignant changes by causing DNA damage and

genomic instability. This involves the generation of reactive oxygen species, expression of proteins that interfere with DNA repair enzymes, and HCV induced activation of a mutator enzyme.[35][36]

Cirrhosis

alcohol use disorder
– the cause of cirrhosis in this case.

In addition to virus-related

primary biliary cirrhosis.[38]

Aflatoxin

epigenetic alterations,[42] is likely a common cause of aflatoxin-induced carcinogenesis
.

Nonalcoholic steatohepatitis (NASH) and Nonalcoholic fatty liver (NAFL)

NASH and NAFL is beginning to be called a risk factor for liver cancer, particularly HCC.[43] In recent years, there has been a noted increase in liver transplantations for HCC that was attributable to NASH.[39] More research is needed in this area and NASH/NAFL.[43]

Other risk factors in adults

Children

Childhood liver cancer is uncommon.[27] The liver cancer sub-types most commonly seen in children are hepatoblastoma, hepatocellular carcinoma, embryomal sarcoma of liver, infantile choriocarcinoma of liver, and biliary rhabdomyosarcoma.[27] Increased risk for liver cancer in children can be caused by Beckwith–Wiedemann syndrome (associated with hepatoblastoma),[49][50] familial adenomatous polyposis (associated with hepatoblastoma),[50] low birth weight (associated with hepatoblastoma),[26] Progressive familial intrahepatic cholestasis (associated with HCC)[51] and Trisomy 18 (associated with hepatoblastoma).[50]

Diagnosis

Further information: Hepatocellular carcinoma § Diagnosis

Many

computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, large lesions are likely to be HCC (e.g., a mass greater than 2 cm has more than 95% chance of being HCC).Given the blood flow to the liver, HCC would be most visible when the contrast flows through the arteries of the liver (also called the arterial phase) rather than when the contrast flows through the veins (also called the venous phase).[17] Sometimes doctors will get a liver biopsy, if they are worried about HCC and the imaging studies (CT or MRI) do not have clear results.[17] 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.[52]

CA125). These tumor markers are found in primary liver cancers, as well as in other cancers and certain other disorders.[53][54]

Prevention

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

hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.[56]

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 can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.[56]

Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of surgical interventions, chemotherapy drugs, and antiviral drugs.[56]

Treatment

General considerations

Like many cancers, treatment depends on the specific type of liver cancer as well as stage of the cancer. The main way cancer is staged is based on the TMN staging systems. There are also liver cancer specific staging systems, each of which has treatment options that may result in a non recurrence of cancer, or cure[57][58] [59] (see Radio Frequency Ablation) For example, for HCC it is common to use the Barcelona Clinic Liver Cancer Staging System.[39]

Treatments include surgery, medications, and ablation methods, which are described in the sections below. There are many chemotherapeutic drugs approved for liver cancer including:

hepatobiliary cancers.[61]

Recent advances in liver cancer treatment are exploring T cells engineered with chimeric antigen receptors (CARs) targeting glypican-3 (GPC3), such as GAP T cells, showing potential in addressing GPC3-positive tumors, especially in pediatric liver cancers.[62][63]

Hepatocellular carcinoma

King Saud Medical Complex, Riyadh, Saudi Arabia

Partial

5-year survival rates after resection have massively improved over the last few decades and can now range from 41 to 74%.[39] However, recurrence rates after resection can exceed 70%, whether due to spread of the initial tumor or formation of new tumors .[64] Liver transplantation can also be considered in cases of HCC where this form of treatment can be tolerated and the tumor fits specific criteria (such as the Milan criteria
). In general, patients who are being considered for liver transplantation have multiple hepatic lesions, severe underlying liver dysfunction, or both.

Percutaneous ablation is the only non-surgical treatment that can offer cure. There are many forms of percutaneous ablation, which consist of either injecting chemicals into the liver (

radio frequency ablation, microwaves, lasers or cryotherapy. Of these, radio frequency ablation has one of the best reputations in HCC, but the limitations include inability to treat tumors close to other organs and blood vessels due to heat generation and the heat sink effect, respectively.[65][66]
In addition, long-term of outcomes of percutaneous ablation procedures for HCC have not been well studied. In general, surgery is the preferred treatment modality when possible.

Systemic

transarterial chemoembolization (TACE). In this procedure, drugs that kill cancer cells and interrupt the blood supply are applied to the tumor. Because most systemic drugs have no efficacy in the treatment of HCC, research into the molecular pathways involved in the production of liver cancer produced sorafenib, a targeted therapy drug that prevents cell proliferation and blood cell growth. Sorafenib obtained FDA approval for the treatment of advanced hepatocellular carcinoma in November 2007.[67] This drug provides a survival benefit for advanced HCC.[66]

Transarterial radioembolization (TRACE) is another option for HCC.[39] In this procedure, radiation treatment is targeted at the tumor. TRACE is still considered an add on treatment rather than the first choice for treatment of HCC,[39] as dual treatments of radiotherapy plus chemoembolization, local chemotherapy, systemic chemotherapy or targeted therapy drugs may show benefit over radiotherapy alone.[68]

Ablation methods (e.g. radiofrequency ablation or microwave ablation) are also an option for HCC treatment.[39][69] This method is recommended for small, localized liver tumors as it is recommended that the area treated with radiofrequency ablation should be 2 centimeters or less.[69]

A surgeon performing photodynamic therapy

Intrahepatic cholangiocarcinoma

Resection is an option in cholangiocarcinoma, but fewer than 30% of cases of cholangiocarcinoma are resectable at diagnosis. The reason the majority of intrahepatic cholangiocarcinomas are not able to be surgically removed is because there are often multiple focal tumors within the liver.

chemoradiation may benefit some cases.[46]

60% of cholangiocarcinomas form in the perihilar region and photodynamic therapy can be used to improve quality of life and survival time in these un-resectable cases.[48] Photodynamic therapy is a novel treatment that uses light activated molecules to treat the tumor. The compounds are activated in the tumor region by laser light, which causes the release of toxic reactive oxygen species, killing tumor cells.[71][73]

Systemic chemotherapies such as gemcitabine and cisplatin are sometimes used in inoperable cases of cholangiocarcinoma.[46]

bile flow, which can decrease the symptoms a patient experiences.[70]

Radiotherapy may be used in the adjuvant setting or for palliative treatment of cholangiocarcinoma.[74]

Hepatoblastoma

Removing the tumor by either

liver transplant can be used in the treatment of hepatoblastoma. In some cases surgery can offer a cure. Chemotherapy may be used before and after surgery and transplant.[75]

Chemotherapy, including cisplatin, vincristine, cyclophosphamide, and doxorubicin are used for the systemic treatment of hepatoblastoma. Out of these drugs, cisplatin seems to be the most effective.[76]

Angiosarcoma and hemangiosarcoma

Many of these tumors end up not being amenable to surgical treatment.[23] Treatment options include surgically removing parts of the liver that are affected.[22] Liver transplantation and chemotherapy are not effective for angiosarcomas and hemangiosarcomas of the liver.[22]

Epidemiology

Deaths from liver cancer per million persons in 2012
  6–18
  19–24
  25–32
  33–40
  41–50
  51–65
  66–72
  73–90
  91–122
  123–479

Globally, liver cancer is common and increasing.[10] Most recent epidemiological data suggests that liver cancer is in the Top 10 for both prevalence and mortality (noted to be the sixth-leading cause of cancer and fourth most-common cause of death).[43] The Global Burden of Disease Liver Cancer Collaboration found that from 1990 to 2015 the new cases of liver cancer per year increased by 75%.[10] Estimates based on most recent data suggest that each year there are 841,000 new liver cancer diagnoses and 782,000 deaths across the globe.[55] Liver cancer is the most common cancer in Egypt, the Gambia, Guinea, Mongolia, Cambodia, and Vietnam.[55] In terms of gender breakdown, globally liver cancer is more common in men than in women.[43][55]

Given that HCC is the most-common type of liver cancer, the areas around the world with the most new cases of HCC each year are Northern and Western Africa as well as Eastern and South-Eastern Asia.

alcohol use that are driving the high levels of HCC.[55]

In terms of intrahepatic cholangiocarcinoma, we currently do not have sufficient epidemiological data because it is a rare cancer. According to the United States National Cancer Institute, the incidence of cholangiocarcinoma is not known. Cholangiocarcinoma also has a significant geographical distribution, with Thailand showing the highest rates worldwide due to the presence of liver fluke.[47][78]

In the United States, there were 42,810 new cases of liver and intrahepatic bile duct cancer in 2020, which represents 2.4% of all new cancer cases in the United States.[79] There are about 89.950 people who have liver and intrahepatic liver cancer in the United States.[79] In terms of mortality, the 5-year survival rate for liver and intrahepatic bile duct cancers in the United States is 19.6%.[79] In the United States, there is an estimated 1% chance of getting liver cancer across the lifespan, which makes this cancer relatively rare.[79] Despite the low number of cases, it is one of the top causes of cancer deaths.[43]

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External links

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