Hepatocellular Carcinoma ( HCC ) is the most common type of primary liver cancer in adults, and is the most common cause of death in people with cirrhosis.
This occurs in the regulation of chronic liver inflammation, and is most closely associated with chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol or aflatoxin. Certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, significantly increase the risk of developing HCC. Metabolic syndrome and NASH are also increasingly known as risk factors for HCC.
As with cancer, the treatment and prognosis of HCC varies depending on the specific histology of the tumor, the size, how far the cancer has spread, and overall health.
Most liver cancers occur in Asia and sub-Saharan Africa, in countries where hepatitis B infection is endemic and many are infected at birth. The incidence of HCC in the United States and other developing countries is increasing due to an increase in hepatitis C virus infection. This is more common in men than women for unknown reasons.
Video Hepatocellular carcinoma
Signs and symptoms
Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may come with a worsening of symptoms or may be asymptomatic at the time of cancer detection. HCC can be present immediately with yellow skin, swollen stomach due to fluid in the abdominal cavity, easy bruising of blood clotting disorders, loss of appetite, unintentional weight loss, stomach pain, nausea, vomiting, or feeling tired.
Maps Hepatocellular carcinoma
Risk factors
HCC occurs mostly in people with cirrhosis of the liver, and therefore common risk factors include factors that cause chronic liver disease that can lead to cirrhosis. However, certain risk factors are much more related to HCC than others. For example, while heavy alcohol consumption is estimated to cause 60-70% of cirrhosis, most liver cancer occurs in cirrhosis associated with viral hepatitis (although there may be overlap). The recognized risk factors include:
- Chronic viral hepatitis (estimated cause of 80% of cases globally)
- Chronic hepatitis B (about 50% of cases)
- Chronic hepatitis C (about 25% of cases)
- Poison:
- Alcohol abuse: the most common cause of cirrhosis
- Aflatoxin
- Excess iron status (Hemochromatosis)
- Metabolic:
- Non-alcoholic steatohepatitis: up to 20% develops into cirrhosis
- Type 2 diabetes (possibly aided by obesity)
- Congenital disorders:
- Alpha 1-antitrypsin Deficiency
- Wilson's disease (controversial, while some theorize increases the risk, case studies are sparse and show otherwise when Wilson's disease can actually provide protection)
- Hemophilia, although statistically associated with higher HCC risks, is due to a chronic viral hepatitis infection simultaneously associated with recurrent blood transfusions over a lifetime.
The importance of these risk factors varies globally. In areas where hepatitis B infection is endemic, like southeastern China, this is a major cause. In populations that are largely protected by hepatitis B vaccination, such as the United States, HCC is most commonly associated with cirrhosis causes such as chronic hepatitis C, obesity, and alcohol abuse.
Certain benign liver tumors, such as hepatocellular adenomas, can sometimes be associated with a malignant HCC that coexists. There is limited evidence for the actual incidence of malignancy associated with benign adenomas; However, the size of the liver adenoma is considered appropriate with the risk of malignancy and larger tumors may be surgically removed. Certain adenoma subtypes, especially those with activation mutations of catena, are particularly associated with an increased risk of HCC.
Children and adolescents may not have chronic liver disease, however, if they suffer from congenital heart disorders, this fact increases the likelihood of developing hepatocellular carcinoma. In particular, children with biliary atresia, infantile colestasis, glycogen storage diseases, and other liver cirrhosis diseases tend to develop HCC in childhood.
Young adults who suffer from rare fibrolamellar variants of hepatocellular carcinoma may not have typical risk factors, namely cirrhosis and hepatitis.
Diabetes mellitus
The risk of hepatocellular carcinoma in type 2 diabetics is greater (from 2.5 to 7.1 times the risk of non diabetes) depending on the duration of diabetes and the treatment protocol. A person suspected of contributing to this increased risk is the concentration of insulin in circulation so that diabetics with poor insulin control or on treatments that increase their insulin output (both countries that contribute to higher circulating insulin concentrations) indicate a much greater risk of carcinoma hepatocellular rather than diabetics in treatments that reduce circulating insulin concentrations. On this note, some diabetics who engage in strict insulin control (by keeping it elevated) show a fairly low level of risk to be differentiated from the general population. This phenomenon is not isolated in type 2 diabetes mellitus because poor insulin regulation is also found in other conditions such as metabolic syndrome (especially, when evidence of non-alcoholic fatty liver disease or NAFLD is present) and again there is evidence of greater risk here. too. Despite claims that users of anabolic steroids are at greater risk (theorized for insulin and exacerbations of IGF), the only confirmed evidence is that users of anabolic steroids are more likely to have hepatocellular adenomas (benign forms of HCC) transformed into more dangerous hepatocellular carcinomas.
Pathogenesis
Hepatocellular carcinomas, like other cancers, develop when there are epigenetic changes and mutations that affect cellular machinery that cause cells to replicate at a higher rate and/or produce cells that avoid apoptosis.
In particular, chronic infections of hepatitis B and/or C may help the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack liver cells, some of which are infected by viruses, others are just observers. Active immune cell inflammatory cells release free radicals, such as reactive oxygen species and reactive species of nitric oxide, which in turn can cause DNA damage and cause mutations of the carcinogenic gene. Reactive oxygen species also cause epigenetic changes at the site of DNA repair.
While a constant damage cycle followed by improvement may cause errors during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, currently, for hepatitis C. Chronic hepatitis C causes HCC through the cirrhosis stage. However, in chronic hepatitis B, integrating viral genomes into infected cells can directly induce liver non-cirrhosis to develop HCC. Or, repeated consumption of ethanol in large quantities can have the same effect. Aflatoxin toxin from certain fungal species is a carcinogen and helps carcinogenesis of hepatocellular cancer by building in the liver. The combined high prevalence of aflatoxin and hepatitis B in settings such as China and West Africa has resulted in a relatively high rate of hepatocellular carcinoma in the region. Other hepatitis viruses such as hepatitis A do not have the potential to become chronic infections and thus are not associated with hepatocellular carcinoma.
Diagnosis
The diagnostic method at HCC has evolved with the improvement of medical imaging. The evaluation of both asymptomatic patients and those with symptoms of liver disease involves blood testing and imaging evaluation. Although historically tumor biopsy is necessary to prove the diagnosis, imaging (especially MRI) findings may be conclusive enough to eliminate histopathologic confirmation.
Screening
HCC remains associated with high mortality rates, partly related to the initial diagnosis that is usually at an advanced stage of the disease. Like other cancers, significant results improve if treatment begins earlier in the disease process. Since most HCC occurs in people with certain chronic liver diseases, especially those with cirrhosis, liver screening is generally recommended in this population. Specific screening guidelines continue to evolve over time as evidence of its clinical impact becomes available. In the United States, the most commonly observed guidelines are those published by the American Association for the Study of Liver Diseases (AASLD). The AASLD recommends screening people with ultrasound cirrhosis every 6 months, with or without blood-pressure measurement of AFP tumor markers. Increases in AFP levels are associated with active HCC disease, although not consistently reliable. At the & gt; 20 sensitivity was 41-65% and specificity was 80-94%. However, at the & gt; the sensitivity of 200 is 31, the specificity is 99%.
In the US, HCC often appears as small hypoechoic lesions with unclear boundaries and irregularly rough internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fat changes, and calcification. This heterogeneity can look similar to cirrhosis and the surrounding liver parenchyma. A systematic review found that the sensitivity was 60 percent (95% CI 44-76%) and the specificity was 97 percent (95% CI 95-98%) compared with pathologic examination of the liver that was detonated or resected as a reference standard. Sensitivity increased to 79% with AFP correlation.
There is still some controversy about the most effective screening protocol. For example, while there are data to support a reduction in mortality associated with screening in people with hepatitis B infection, the AASLD notes that "no randomized [screening test] in Western populations with cirrhosis secondary to chronic hepatitis C or fatty liver disease, and with so there is some controversy surrounding whether supervision really leads to a reduction in mortality in the patient population with cirrhosis. "
High-risk people
In someone where there is a higher suspicion of HCC, such as someone with abnormal blood symptoms or tests (ie, alpha-fetoprotein and des-gamma carboxyprothrombin levels), evaluation requires liver imaging with CT or MRI scans. Optimally, this scan is performed by intravenous contrast in several phases of liver perfusion to improve accurate detection and classification of any liver lesions by the interpreting radiologist. Because of the characteristic blood flow patterns of HCC tumors, specific perfusion patterns of any liver lesions detected can conclusively detect HCC tumors. Alternatively, scanning can detect uncertain lesions and further evaluation can be done by obtaining a physical sample of the lesion.
Imaging
Ultrasound, CT scan, and MRI can be used to evaluate the liver for HCC. In CT and MRI, HCC can have three different growth patterns:
- Large single tumor
- Some tumors
- Unclear tumors with infiltrative growth patterns
A systematic review of CT diagnosis found that the sensitivity was 68 percent (95% CI 55-80%) and specificity was 93 percent (95% CI 89-96%) compared with liver pathologic examination extracted or resected as a reference standard.. With triple-phase helical CT, the sensitivity is 90% or higher, but this data has not been confirmed with autopsy studies.
However, MRI has the advantage of providing liverless images without high resolution without ionizing radiation. HCC appears as a high-intensity pattern on T2-weighted images and low intensity patterns on a weighted T1 image. The advantage of MRI is that it has increased sensitivity and specificity when compared with US and CT in cirrhotic patients with whom it is difficult to distinguish HCC from regenerative nodules. A systematic review found that the sensitivity was 81 percent (95% CI 70-91%) and specificity was 85 percent (95% CI 77-93%) compared with pathologic examination of the liver that was detonated or resected as a reference standard. Sensitivity increases further when enhanced and diffusion gadolinium contrast imaging is combined.
MRI is more sensitive and specific than CT.
Liver Image Reporting and Data System (LI-RADS) is a classification system for reporting liver lesions detected on CT and MRI. Radiologists use this standardized system to report suspicious lesions and provide possible alleged malignancies. Categories range from LI-RADS (LR) 1 to 5, in order to concern for cancer. A biopsy is not necessary to confirm the diagnosis of HCC if certain imaging criteria are met.
Pathology
Macroscopically, liver cancer presents as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). The tumor nodule is round to oval, gray or green (if the tumor produces bile), well constrained but not encapsulated. The diffuse type is less restricted and infiltrated the portal vein, or hepatic vein (rare).
Microscopically, there are four architectural and cytology types (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular (adenoid), pleomorphic (cell giant) and clear cell. In well-differentiated form, tumor cells resemble hepatocytes, forming trabeculae, ropes, and nests, and may contain bile pigment in the cytoplasm. In less undifferentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, gigantic. Tumors have a slight stroma and central necrosis due to poor vascularization.
Staging
The prognosis of HCC is influenced by tumor staging and liver function due to cirrhosis of the liver.
There are a number of staging classifications for available HCC; However, because of the unique nature of carcinoma to fully encompass all features affecting HCC categorization, the classification system should combine; size and number of tumors, presence of vascular invasion and extrahepatic spread, liver function (serum bilirubin and albumin levels, presence of ascites and portal hypertension) and general patient health status (determined by ECOG classification and presence of symptoms).
Of all the staging classification systems available classification of cancer Barcelona Heart Clinic (BCLC) includes all the above characteristics. This staging classification can be used to select people for treatment.
The essential features that guide the treatment include the following:
- size
- spread (stage)
- involvement of the liver vessels
- the presence of a tumor capsule
- the presence of extrahepatic metastases
- the existence of child nodules
- tumor vascularity
MRI is the best imaging method for detecting the presence of tumor capsules.
The most common metastatic sites are the lungs, abdominal lymph nodes, and bones.
Prevention
Because hepatitis B or C is one of the leading causes of liver cancer, prevention of this infection is key to then preventing liver cancer. Thus, vaccination of children against hepatitis B can reduce the risk of liver cancer in the future.
In the case of patients with cirrhosis, alcohol consumption should be avoided. Also, screening for hemochromatosis may be helpful for some patients.
It is not clear whether screening them with chronic liver disease for hepatocellular carcinoma improves outcomes.
Treatment
Treatment of hepatocellular carcinoma varies based on the stage of the disease, the likelihood of a person to tolerate surgery, and the availability of liver transplantation:
- Curative intent: for a limited disease, when the cancer is confined to one or more areas of the liver, surgery removing malignant cells may be curative. This can be done by resection of the affected part of the liver (partial hepatectomy) or in some cases by orthotopic liver transplant from all organs.
- "Bridging" the intention: for a limited illness qualified for a potential liver transplant, the person may undergo targeted treatment for some or all of the known tumors while waiting for donor organs to be available.
- "Downstaging" intent: for advanced moderate disease that has not spread beyond the liver, but is too advanced to qualify for healing treatment. The person can be treated with targeted therapy to reduce the size or number of active tumors, with the goal of once again eligible for liver transplant after this treatment.
- Palliative intent: for more advanced illnesses, including the spread of cancer outside the liver or in people who can not tolerate surgery, treatment is intended to reduce the symptoms of the disease and maximize the duration of survival.
Loko-regional therapy (also referred to as liver-directed therapy) refers to one of several minimally invasive treatment techniques to focally target HCC in the liver. These procedures are an alternative to surgery, and may be considered in combination with other strategies, such as liver transplant later in life. Generally, this treatment procedure is performed by a radiologist or intervention surgeon, in coordination with a medical oncologist. Loko-regional therapy may refer either to percutaneous therapy (eg cryoablation), or arterial catheter-based therapy (chemoembolization or radioembolization).
Surgical resection
Surgical removal of the tumor is associated with a better prognosis of cancer, but only 10-15% of patients are suitable for surgical resection due to illness or liver function. Surgery is only considered if the entire tumor can be removed safely while keeping the functional liver sufficient to maintain normal physiology. Thus, pre-operative imaging assessments are essential to determine both HCC levels and to estimate the remaining amount of liver remaining after surgery. To maintain liver function, residual liver volume should exceed 25% of total liver volume in non-ailing liver, more than 40% in liver cirrhosis. Surgery in a diseased liver or cirrhosis is commonly associated with higher morbidity and mortality. The overall recurrence rate after resection is 50-60%. The Singapore Liver Cancer Recurrence score (SLICER) can be used to estimate the risk of recurrence after surgery.
Liver transplant
Liver transplant, replacing liver diseased with cadaver or live donor liver, plays an increasing role in HCC treatment. Although the results after liver transplant were initially poor (20% -36% survival rate), results have improved significantly with improvements in surgical techniques and adoption of Milan criteria at US transplant centers. The expanded Shanghai criteria in China have resulted in overall disease-free survival and disease-free survival similar to those achieved using the Milan criteria. Studies from the late 2000s gained a higher survival rate, ranging from 67% to 91%.
In diseases that have spread beyond the liver, systemic therapy can be a consideration. In 2007, sorafenib, an oral multicinase inhibitor, was the first systemic agent approved for advanced HCC first-line treatment. Experiments have found modest improvements in overall survival: 10.7 months vs. 7.9 months and 6.5 months vs. 4.2 months.
The most common side effects of sorafenib include hand-foot skin reactions and diarrhea. Sorafenib is thought to work by blocking the growth of tumor cells and new blood vessels. Many other molecular target drugs are being tested as the first and second alternative treatment for advanced HCC.
More
- Portal Vein Embolization (PVE): This technique is sometimes used to increase the volume of a healthy liver, to increase the likelihood of survival after surgical removal of a diseased liver. For example, embolization of the right main portal vein will result in compensatory hypertrophy of the left lobe, which may qualify the patient for partial hepatectomy. Embolization was performed by an interventional radiologist using a percutaneous transhepatic approach. This procedure can also serve as a bridge for transplantation.
- High intensity focused ultrasound (HIFU) (compared with diagnostic ultrasound) is an experimental technique that uses high-powered ultrasound waves to destroy tumor tissue.
- The systematic review assessed 12 articles involving a total of 318 patients with hepatocellular carcinoma treated with radioembolization of Yttrium-90. Excluding one patient's only study, postoperative CT CTT evaluation showed a response ranging from 29 to 100% of patients evaluated, with all but two studies showing a response of 71% or greater.
Prognosis
The usual result is bad, because only 10-20% of hepatocellular carcinoma can be fully removed using surgery. If the cancer can not be completely eliminated, the disease is usually lethal in 3 to 6 months. This is partly due to the late presentation with tumors, but also the lack of expertise and medical facilities in areas with high HCC prevalence. However, survival may vary, and sometimes people will last longer than 6 months. The prognosis for metastatic or inoperable hepatocellular carcinoma has recently increased due to the approval of sorafenib (NexavarÃ,®) for advanced hepatocellular carcinoma.
Epidemiology
HCC is one of the most common tumors in the world. HCC epidemiology shows two major patterns, one in North America and Western Europe and one in non-Western countries, such as in sub-Saharan Africa, Central and Southeast Asia, and the Amazon basin. Men are more affected than the usual and most common women between the ages of 30 and 50, hepatocellular carcinoma accounts for 662,000 deaths worldwide per year about half in China.
Africa and Asia
In some parts of the world, such as sub-Saharan Africa and Southeast Asia, liver cancer is the most common cancer, commonly affecting males more than females, and with the onset of age between late adolescents and 30s. This variability is partly due to the different patterns of hepatitis B and hepatitis C transmission in different populations - infection in or around birth affects cancer earlier than if people were infected later. The time between hepatitis B infection and development into HCC can be years, even decades, but from HCC diagnosis to death, the average survival period is only 5.9 months according to a Chinese study during 1970-1980, or 3 months ( time of average survival) in Sub-Saharan Africa according to Manson's textbook on tropical diseases. HCC is one of the most deadly cancers in China where chronic hepatitis B is found in 90% of cases. In Japan, chronic hepatitis C is associated with 90% of HCC cases. Foods infected with Aspergillus flavus (especially nuts and corn stored during prolonged wet seasons) that produce aflatoxin cause other risk factors for HCC.
In the East Asian hemisphere, hepatocellular carcinoma (HCC) is the most common type of cancer. A common risk factor for HCC in Asia is a high diagnosis of Hepatitis B. However, in Japan the common risk factor is hepatitis C. Another factor is that causes HCC is a mycotoxin called aflatoxin. This mycotoxin is found in many regions of Asia with South China being an Asian country with the highest number of aflatoxins. Thus, China is the country with the highest HCC diagnosis in East Asia.
North America and Western Europe
The most common malignant tumors in the liver represent metastasis (spread) from tumors that originate from elsewhere in the body. Among the cancers that come from liver tissue, liver cancer is the most common primary liver cancer. In the United States, US surveillance, epidemiology and outcome (SEER) surveillance database programs show that HCC accounts for 65% of all cases of liver cancer. Because there are on-site screening programs for high-risk people with chronic liver disease, HCC is often found much earlier in Western countries than in developing regions such as Sub-Saharan Africa.
Acute and chronic liver porphyria (acute intermittent porphyria, cutanea tarda porphyria, hereditary coproporphyria, porphyria variegate) and type I tyrosinemia are risk factors for hepatocellular carcinoma. The diagnosis of acute hepatic porphyria (AIP, HCP, VP) should be sought in patients with hepatocellular carcinoma without risk factors typical of hepatitis B or C, alcoholic liver cirrhosis or hemochromatosis. Both active and latent genetic carriers of acute hepatic porphyry are at risk for this cancer, although latent genetic carriers have developed cancer at a later age than those with classic symptoms. Patients with acute hepatic porphyria should be monitored for hepatocellular carcinoma.
The incidence of HCC is relatively lower in the west than in East Asia. However, despite its low statistics, there is an increase in HCC in the West. The diagnosis of HCC has increased since the 1980s and continues to increase, making it one of the causes of increased cancer deaths. The common risk factors for HCC are hepatitis C, along with other health problems.
Research
Pre-clinical
Current research includes looking for unregulated gene in HCC, anti-heparanase antibodies, protein markers, non-coding RNA (such as TUC338) and other predictive biomarkers. Because similar studies produce results in other malignant diseases, it is hoped to identify deviant genes and the resulting protein may lead to the identification of pharmacologic interventions for HCC.
The development of a three-dimensional culture method provides a new approach to the preclinical study of cancer therapy using patient-derived organoids. This 'miniature organoid' avatar of patient tumors recapitulates some features of the original tumor, making them an attractive model for drug sensitivity testing and precision drugs for HCC and other types of primary liver cancer.
Furthermore, hepatocellular carcinoma (HCC) is a type of cancer that occurs in patients with liver disease. Biomarkers marked with six-MiRNAs allow for effective treatment in patients with HCC and are able to predict their recurrence at heart.
Clinical
JX-594, oncolytic virus, has an orphan drug designation for this condition and is undergoing clinical trials.
Hepcortespenlisimut-L (Hepko-V5), oral cancer vaccine also has the US FDA orphan drug labeling for hepatocellular carcinoma. Immunitor Inc. completed the Phase II trial, which was published in 2017.
A randomized trial of people with advanced HCC showed no benefit to the combination of everolimus and pasireotide.
Abbreviation
HCC, hepatocellular carcinoma; TACE, transarterial embolization/chemoembolization; PFS, progression-free survival; PS, appearance status; HBV, hepatitis B virus; PEI, percutaneous ethanol injection; RFA, radio frequency ablation; RR, response rate; MS, average survival.
See also
- Hemihipertropfi
- Oncovirus
- Portal hypertension
References
Further reading
- "Long-term outcome of liver transplantation for hepatocellular carcinoma: an update of the Padova University experience". September 23, 2013 . Retrieved February 6 2014 .
- Bruix, Jordi; Sherman, Morris; Committee on Practice Guidelines (November 2005). "Management of hepatocellular carcinoma". Hepatology . 42 (5): 1208-1236. doi: 10.1002/hep.20933. PMIDÃ, 25 16250051.
- Liu, Chi-leung, M.D., "Hepatic Rescue for Hepatocellular Carcinoma", Hong Kong Health Diary , Vol.10 No.12, December 2005 Medical Bulletin
External links
- NCI Liver Cancer Homepage
- Blue Faery: Adrienne Wilson's Liver Cancer Association
- Liver cancer picture from Mayo Clinic
Source of the article : Wikipedia
0 Comments