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Hepatocellular carcinoma is a primary malignant liver cell tumor. In most cases, it develops on the basis of liver cirrhosis or chronic hepatitis.

Definition

Hepatocellular carcinoma, abbreviated to HCC, is a malignant disease of the liver that develops directly from the liver cells. It is also referred to as primary liver cancer. As a rule, hepatocellular carcinoma is preceded by chronic liver cell damage. The symptoms are usually non-specific and the disease is often only diagnosed at a late stage. A liver resection or liver transplant is almost always the only curative treatment available. Often, only palliative measures can make the patient's life easier. Secondary liver tumors that spread from other primary foci are far more common than primary hepatocellular cancer. They are usually metastases of colorectal and other gastrointestinal carcinomas as well as breast or lung cancer. Secondary liver malignancies differ from primary liver tumors in terms of treatment and progression. The following text deals only with primary hepatocellular carcinomas.

Epidemiology

Hepatocellular carcinoma is the sixth most common malignant tumor disease worldwide. In 2018, more than 841,000 new primary liver malignancies were diagnosed, with 782,000 patients suffering a fatal outcome [1].

The incidence in the individual countries is heterogeneous due to the risk factors. Up to 80 percent of global cases are found in South-East Asian regions and countries on the African continent south of the Sahara. Although the incidence of HCC is much lower in Europe, the USA and Japan, a continuous increase has also been recorded here for years. For example, the incidence of hepatocellular cancer in the USA has tripled in the last four decades. This is due to chronic HCV infection-related liver cirrhosis as well as a significant increase in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty liver hepatitis (NASH) with advanced fibrosis or cirrhosis.

On average, men develop the disease at the age of 71, women at 74. Overall, one in 88 men and one in 190 women will develop a malignant liver tumor during their lifetime. This means that men are two to three times more likely to be affected by liver cancer than women. The relative 5-year survival rate for men and women is around 15 percent.

Risk factors

The most common risk factors for HCC in Germany are currently chronic infection with the hepatitis C virus (HCV) and alcohol abuse. According to studies, excessive alcohol consumption is responsible for 15 percent of new liver malignancies in women and 35 percent in men.

In South-East Asian regions and sub-Saharan African countries, the high number of cases is mainly due to chronic infections with the hepatitis B virus (HBV) and the consumption of food containing the mold toxin aflatoxin B1.

The most significant risk factors in the western world are chronic HCV infection-related liver cirrhosis as well as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty liver hepatitis (NASH) with advanced fibrosis or cirrhosis. The latter can be the result of diabetes mellitus or metabolic syndrome. Obesity is often the underlying cause.

Other risk factors are hereditary metabolic diseases such as haemochromatosis, porphyria or alpha-1-antitrypsin deficiency. In principle, every patient with liver cirrhosis - regardless of the underlying etiology - has an increased risk of HCC. The relative risk varies depending on the cause. Cohort studies show that around 1 to 8 percent of all patients with cirrhosis develop hepatocellular carcinoma (2% with HBV, 3-8% with HCV).

Causes

All hepatocellular cirrhosis is associated with an increased risk of HCC, regardless of the cause. The following causes are distinguished in the development of liver cirrhosis and thus also liver cancer:

Toxic:

  • chronic alcohol abuse (most common cause)
  • drugs that damage liver cells, for example cytostatics such as methotrexate, tetracyclines, phenothiazines, paracetamol and amiodarone, as well as long-term misuse of androgens
  • Environmental toxins such as aflatoxin (especially B1), areca nut (betel nut)
  • Nicotine abuse
  • organic solvents such as toluene and xylene
  • Exposure to hepatotoxic substances, for example tetrachloromethane (in metal processing), arsenic, N-nitrosamines, phosphorus and various ingredients in pesticides (especially dichlorodiphenyltrichloroethane, DDT)
  • certain plant and plant components (potentially liver-damaging are celandine, kava-kava, sea holly, gamander, lycopodium, chaparral, pole mint and mulberry as well as herbs and teas containing pyrrolizidine alkaloids)

Inflammatory:

  • chronic viral infections with hepatitis virus B, hepatitis C or hepatitis D (second most common cause of liver cirrhosis)
  • all chronic biliary tract diseases with cholestasis such as primary biliary cholangitis and primary/secondary sclerosing cholangitis
  • Tropical diseases such as yellow fever or dengue fever
  • Immunoglobulin G4-associated cholangiopathy
  • Autoimmune hepatitis
  • bacterial infections such as brucellosis, BCG sepsis, listeriosis, lues III or typhoid fever
  • Mycoses, especially Candida infections and histoplasmosis
  • Parasites, for example after amoeba and echinococcus infestation
  • Schistosomiasis (liver fluke)
  • Malaria
  • Schistosomiasis
  • visceral leishmaniasis

Metabolic:

  • non-alcoholic fatty liver disease (NAFLD)
  • non-alcoholic fatty liver hepatitis (NASH)
  • Diabetes mellitus type II,
  • Obesity
  • Dyslipidemia
  • α1-antitrypsin deficiency
  • Haemochromatosis
  • Wilson's disease
  • Tyrosinemia type I
  • Cystic fibrosis
  • Hereditary fructose intolerance
  • Porphyrin accumulation in porphyrias such as acute hepatic porphyria, cutaneous porphyria or congenital erythropoietic porphyria (Günther's disease)
  • Glycogen accumulation in glycogenoses, for example von Gierke's disease, Forbes' disease or Pompe's disease

Chronic congestion of the hepatic veins:

  • Budd-Chiari syndrome (hepatic vein obstruction due to thrombosis)
  • Cirrhosis cardiaque (hepatic vein congestion in right heart failure)
  • Osler's disease (pseudocirrhosis due to fibrous septa, arteriovenous fistulas and hemorrhagic telangiectasia)

Cryptogenic genesis:

  • hitherto unclear aetiology

Recent studies indicate that microbiota also play a role in carcinogenesis. Biomarkers in the intestinal microbiome could even represent potential non-invasive tools for the early detection of HCC.

Pathogenesis

In most cases, liver cancer develops on the basis of liver cirrhosis. During hepatocarcinogenesis, proliferation and growth of hepatocytes change. DNA sequence changes in the form of mutations influence the resistance of the cells to apoptosis. This allows altered tumor cells to proliferate without being destroyed by the programmed suicide program. Changes in the p53 tumor suppressor gene are found in up to 50 percent of all hepatocellular carcinomas. In more than 60 percent, a loss of heterozygosity can be detected in the gene that codes for the insulin-like growth factor receptor 2 (IGFR2). As a result, the proliferation-inhibiting effect of this receptor is reduced, which leads to overexpression of IGF2 and hyperproliferation of the tumor cells. In 80 percent of cases, other regulatory mechanisms that inhibit cell proliferation are also defective. One of these is the retinoblastoma (Rb) signaling pathway. This results in overexpression of the oncoprotein gankyrin, which inhibits the tumor suppressor protein Rb protein and the tumor suppressor gene p53. Other molecular changes affect replicative cell ageing and thus the senescence program. The shorter the telomeres become with each cell division, the less protected the chromosomal DNA is. In addition, mutated oncogene (MYC, PI3K/Akt, PTEN) and developmental signaling pathways (Wnt, Hedgehog, MET) are found. The molecular changes in HCC are not always the same; rather, they depend on the underlying liver disease.

Spread and growth of HCC

Hepatocellular carcinoma shows three growth patterns:

  • Unifocal: solitary, usually massive tumor findings
  • Multifocal: multiple malignant tumor cell nests that can occur throughout the entire liver structure
  • Diffuse infiltrative: diffuse growth of tumor cells over the entire liver

Hepatocellular carcinomas often grow rapidly into surrounding blood vessels, such as the portal veins or inferior vena cava. HCC also frequently forms metastases, particularly in the regional lymph nodes as well as in the adrenal glands, lungs and skeletal system.

Histology

Depending on the cytology and cytoarchitecture, hepatocellular carcinomas are differentiated according to the following histopathological features:

  • Solid-trabecular HCC: Liver tissue with a trabecular and sinusoidal structure, the regular lobular architecture is abolished. The tumor cells show trabecular growth with a shifted nuclear-cytoplasmic relation, basophilia of the cytoplasm and nuclear accumulation. The trabeculae are usually more than three cell layers wide.
  • Acinar/pseudoglandular HCC: The tumor cells often grow as a single-row formation and show PAS-positive material in the clearing.
  • Compact HCC type: The tumor cells grow in solid formations, so that the trabecular structure is often no longer or only poorly recognizable. The tumor cells are often less differentiated than in the trabecular form.
  • Fibrolamellar HCC: Special form, accounts for around 1 percent of all hepatocellular carcinomas; characterized by broad fibrolamellar septa of collagenous connective tissue in which the tumour cells are "walled in". Fibrolamellar HCC occurs predominantly in younger patients without liver cirrhosis.

Symptoms

Initially, liver cancer usually causes no symptoms. If the hepatocellular carcinoma becomes symptomatic, the symptoms are often non-specific and the tumor is already at an advanced stage.

The following symptoms may indicate HCC:

  • Pain in the right upper abdomen or a feeling of pressure due to expansion of the liver capsule
  • palpable swelling under the right costal arch
  • Ascites
  • Inappetence
  • Nausea and vomiting
  • increased temperature of unknown origin
  • Weakness
  • Reduced performance
  • unintentional weight loss, later tumor cachexia
  • Jaundice
  • Signs of decompensated liver cirrhosis with oesophageal variceal bleeding, hepatic encephalopathy and hepatopulmonary syndrome

Diagnostics

Liver cancer is suspected on the basis of the patient's medical history, clinic and physical examination. This is followed by blood and urine tests. Alpha-fetoprotein (AFP) is a tumor marker for the early detection and later monitoring of hepatocellular carcinoma. All liver function parameters are also determined.

The type and spread of the tumor is determined using imaging techniques (with and without contrast agent). These may include

  • Sonography
  • Computed tomography (CT) of the thorax and abdomen
  • Magnetic resonance imaging (MRI) with contrast medium
  • Liver puncture with biopsy and conventional histopathology
  • Confirmation of the diagnosis by means of immunohistological and/or molecular pathological examinations
  • Skeletal scintigraphy
  • if secondary tumors are suspected: gastroscopy and/or colonoscopy

Classification and tumor staging

Hepatocellular carcinoma is usually classified according to the TNM scheme and UICC staging. Internationally, grading is based on the WHO system and the Edmondson and Steiner grading system. Treatment regimes and prognostic predictions are primarily based on the Barcelona Classification (BCLC).

BCLC classification

In addition to tumor size, the Barcelona classification includes the patient's general condition according to performance status (PS) and liver function based on the CHILD score. The stage-appropriate treatment and prognosis of HCC is based on this. The general or performance status was defined by the WHO and the ECOG (Eastern Cooperative Oncology Group):

  • 0: Normal everyday activity, no restrictions
  • 1: Restrictions on physical exertion, patient is able to walk, light physical work is feasible
  • 2: Patient is able to walk, self-care still possible but unable to work, patient can stand up for more than 50% of waking time
  • 3: Self-care only possible to a limited extent, the patient is forced to spend 50% of waking time sitting or lying down
  • 4: Complete dependency on care, self-care no longer possible, patient spends the entire day and night sitting or lying down
  • 5: Death

The BCLC stages are defined as follows:

  • Stage 0: WHO/ECOG 0, single primary tumor < 2 cm or carcinoma in situ, no liver cirrhosis or maximum CHILD A
  • Stage A (early stage): WHO/ECOG 0, small singular primary tumor, liver cirrhosis without symptoms
    • Stage A1: WHO/ECOG 0, solitary primary tumor < 5 cm, no portal hypertension (HPVG < 10mmHg), bilirubin normalo
    • Stage A2: WHO/ECOG 0, solitary primary tumor < 5 cm, portal hypertension, normal bilirubin
    • Stage A3: WHO/ECOG 0, solitary primary tumor < 5 cm, portal hypertension, bilirubin elevatedo
    • Stage A4: WHO/ECOG 0, ≤ 3 primary tumors < 3 cm, CHILD A or B
  • Stage B (intermediate stage): WHO/ECOG 0, multilocular involvement, tumor foci > 3 cm, CHILD A or B
  • Stage C (advanced stage): WHO/ECOG 1-2, same as B plus additional vascular invasion or distant metastases, CHILD A or B
  • Stage D (terminal stage): WHO/ECOG 3-4, all higher grade findings, CHILD C

Therapy

Without vascular invasion and without distant metastases, three curative treatment methods are available for HCC (BCLC stages A and B):

  • Surgery or surgical resection
  • orthotopic liver transplantation
  • Tumor ablation

The individual treatment regimen depends on the size, location and number of tumors, residual liver function, general condition and any accompanying comorbidities. The decision for an optimal treatment strategy should be made in an interdisciplinary tumor conference, taking into account surgical, local ablative and system therapeutic options. In addition to a radiologist experienced in interventional oncology and a surgeon experienced in hepatobiliary surgery, the presence of hepatologists/oncologists, pathologists and radiation oncologists is advisable.

Surgery

Hepatocellular carcinoma responds poorly or not at all to conventional cytostatics. For this reason, hepatocellular carcinomas are treated with stage-dependent surgical intervention.

If the hepatocellular carcinoma is not based on liver cirrhosis, surgical resection is the treatment of choice. If the tumor tissue can be completely resected with a sufficient safety margin in healthy tissue, curative therapy is likely to be successful - however, the recurrence rates after such interventions are quite high. With all forms of therapy (with the exception of liver transplantation), recurrences or second tumors occur in up to 80 percent of cases within five years, even in early tumor stages.

Before an operation, liver function should generally be checked on an interdisciplinary basis and the risk of postoperative liver failure should be taken into consideration. In the case of liver cirrhosis, there is often not enough functioning residual tissue remaining after a potentially curative tumor resection to maintain liver function.

A hepatocellular carcinoma diagnosed at an early stage can be treated surgically under certain circumstances, even with concomitant liver cirrhosis. For some patients, a subsequent liver transplant is a suitable option. This not only eliminates the tumor, but also the liver cirrhosis.

Liver transplantation

Patients with curatively treatable hepatocellular carcinoma should be referred to a liver transplant center. However, liver transplantation is only indicated as long as there is no extrahepatic manifestation (cN0M0) and no macrovascular invasion of the liver vessels (cV0).

In stage BCLC A, the recurrence rates after transplantation are low at around 10 to 12 percent. This results in the best long-term survival rates (with adequate patient selection). Transplantation is therefore the most effective of the available treatment options.

The exact indication for liver transplantation is based on the Milan criteria. For example, the singular HCC focus must be smaller than 5 cm. Otherwise, a maximum of three HCC foci may be present, which do not measure more than 3 cm in diameter at their largest extent. In order to achieve the Milan criteria, an attempt can be made to reduce the size of the tumor prior to a transplant. Such downstaging is usually performed using local ablation (RFA), liver resection or a transarterial procedure (TACE, TARE).

If a transplant is not an option, it must be checked whether the carcinoma can be surgically removed at all. This depends on the size of the tumor, its location, liver function, the presence of portal hypertension and the patient's general condition.

Interventional treatment methods

Typical local procedures are

  • Tumour embolization as transarterial chemoembolization (TACE) or transarterial embolization (TAE)
  • Transarterial radioembolization (TARE) or selective internal radiotherapy (SIRT)
  • Radiofrequency ablation (RFA, RFTA, RITA)
  • Microwave ablation (MWA)Ablation with high-intensity focused ultrasound (HIFU)
  • Irreversible electroporation (IRE)Laser-induced thermotherapy (LITT)
  • High-frequency induced thermotherapy (HITT)
  • Percutaneous ethanol injection (PEI)
  • High-precision radiotherapy (SBRT)

In addition to the downstaging method, interventional procedures are also suitable as palliative measures to improve the patient's life situation.

Transarterial interventions (TACE, TAE and TAC): Transarterial chemoembolization (TACE) or transarterial embolization (TAE) and transarterial chemoperfusion (TAC) are local treatment procedures that combine the principles of embolization and chemotherapy. After local anesthetic treatment, a catheter is inserted from the groin to the hepatic artery supplying the tumor. A chemotherapeutic lipiodol emulsion is then injected, which is retained by the tumor cells. In addition, a temporary vascular occlusion occurs. The main effect of TACE appears to be based on tumour embolization.

It is also possible to apply so-called "drug-eluting beads" (DEB). The non-absorbable hydrogel spheres, which can be loaded with chemotherapeutic agents (mitomycin, doxorubicin or epirubicin), enable a delayed release of the chemotherapeutic agent. This increases the intratumoral concentration of the cytostatic drug while simultaneously occluding the tumor vessels. Conventional TACE and drug-eluting TACE can be regarded as equivalent procedures.

In addition, TACE can be combined with drug treatment (sorafenib) or other local ablative methods (e.g. RFA).

Chemoembolization is primarily used to treat multifocal tumour foci that cannot be removed surgically or by local ablation and which do not show any vascular invasion or distant metastases on imaging. Chemo-embolization delays tumour growth and improves survival. TACE should be repeated as long as patients respond to it and treatable hypervascularized tumour parts remain.

The method is only suitable for patients with sufficiently preserved liver function.

Transarterial radioembolization (TARE) or selective internal radiotherapy (SIRT): Transarterial radioembolization (TARE) or selective internal radiotherapy (SIRT) can be used instead of TACE in patients with preserved liver function in the intermediate stage of HCC as decided by the tumour board. In this local transvascular radiation treatment, tiny beads loaded with a radioactive substance (with a very short range) are introduced directly into the vessels that supply the liver tumor. A so-called ß-emitter (90 yttrium encapsulated in microspheres) is injected into the hepatic propria artery and its branches via the groin using a catheter. This exposes the malignant cells to a high local dose of radiation and closes off the vessels supplying the tumor. The radioactivity must be applied with pinpoint accuracy. A leakage of the radioactive microspheres into other abdominal blood vessels would cause considerable side effects.

Radiofrequency ablation (RFA): In radiofrequency ablation (= radiofrequency-induced thermotherapy/thermoablation: RFA, RFTA, RITA), electrodes are inserted into the tumor tissue via an ablation catheter. The malignant tumor is heated to over 100°C using pulsed high-frequency current. The malignant cells are killed as a result of heat necrosis. RFA is performed under ultrasound or CT control. The method is suitable for tumors between 3 and 5 cm in diameter. There is a very good chance of success, especially with fewer than four tumor foci > than 3 cm.

For tumors 3 to 5 cm in diameter, RFA can also be used in combination with TACE/TAE. In this case, the tumour is first marked and reduced in size by (chemo)embolization and the remaining tumour cells are then destroyed using RFA [18].

Microwave ablation (MWA): For a long time, radiofrequency ablation was established as the only standard method of percutaneous local ablation. Based on new studies, the current guideline now classifies microwave ablation (MWA) as equivalent. Compared to RFA, microwave ablation (MWA) can generate higher temperatures (up to 160°C). The procedure is therefore suitable for HCC foci that are located close to large, well-perfused vessels (portal vein, hepatic vein star).

Ablation with high-intensity focused ultrasound (HIFU): Ablation with high-intensity focused ultrasound (HIFU) enables targeted and gentle destruction of malignant tumor cells. Focused ultrasound waves are applied to the tumor tissue. As a result, the temperature in the tumor area rises to up to 80 degrees Celsius, which destroys the malignant cells. HIFU is particularly suitable for small HCC foci (less than 2-3 cm). So far, however, there are only very few centers in Germany that offer HIFU. Note: The procedure is not yet listed in the current guideline.

Irreversible electroporation (IRE): Irreversible electroporation (IRE) or non-thermal irreversible electroporation (NTIRE) is a relatively new, minimally invasive technique. In this non-thermal ablation procedure, strong, localized short-pulsed electric fields destroy the tumour cells in a targeted manner. More precisely, the phospho-dilipid layers of the cell membrane are damaged through nano-sized pores. Once a certain level of damage has been reached, the tumor cells are no longer viable and are eliminated by apoptosis. IRE does not permanently damage blood vessels or other structures. This is why this procedure is particularly suitable for complicated HCC. The use of IRE is also currently limited to only a few centers and offers a potential advantage for the treatment of HCC close to the bile ducts due to the low thermal effect - however, studies with a sufficient number of patients or long survival data are currently still lacking.

According to the current guideline, irreversible electroporation should not be used to treat hepatocellular carcinomas that are suitable for resection or thermal ablation with RFA/MWA due to the small number of clinical studies. The local recurrence rate after IRE is significantly higher for HCC > 2.5 cm than after treatment with RFA, MWA or resection.

Laser-induced thermotherapy (LITT) and high-frequency-induced thermotherapy (HITT): In laser-induced thermotherapy (LITT), laser light with a wavelength of 1064 nm is directed onto the malignant cells via a laser applicator placed in the tumor tissue using glass fibers. These are directly heated and destroyed under ultrasound or CT control. In high-frequency induced thermotherapy (HITT), high-frequency electric beams are used instead of laser beams. These generate a resistance heat of 70 to 100 degrees Celsius in the tumor tissue. As with LITT, the cancer cells are destroyed.

Due to a very small number of clinical studies, laser ablation should not be used to treat HCCs that are eligible for resection or thermal ablation with RFA/MWA.

Percutaneous ethanol injection (PEI): Percutaneous ethanol injection is the oldest clinically used percutaneous treatment method for HCC. In this method, 95% alcohol is injected into the tumor under ultrasound or CT guidance. This kills the tumor without damaging the surrounding healthy liver tissue. According to the new guideline, PEI is no longer recommended, as studies have shown the clear superiority of RFA [2].

High-precision radiotherapy (SBRT): High-precision radiotherapy (stereotactic body radiotherapy; SBRT) can be considered if alternative treatment methods are not possible ¬- for example, if there is a high probability of treatment failure, impaired liver function or technical obstacles [2].

Systemic therapy

In the majority of patients, the hepatocellular carcinoma is already so advanced at the time of diagnosis that surgery or local destruction of the tumor is no longer possible. Systemic chemotherapy is also not very promising for most HCC patients. This is where targeted drug therapies come into play. At the time of the last guideline, only sorafenib could be recommended based on evidence. There is now further evidence of efficacy in the treatment of advanced liver carcinoma.

First-line therapy

According to the current guideline, first-line therapy with the combination of the antibodies atezolizumab against PD-L1 and bevacizumab against VEGF (A+B) should be offered to HCC patients:

  • in Child-Pugh stage A and BCLC B or C
  • with distant metastases
  • a tumor location that cannot be controlled or resected locally.

If there is a contraindication for A+B, first-line therapy with one of the two tyrosine kinase inhibitors sorafenib or lenvatinib is an alternative.

Drug therapy after failure, intolerance or contraindications of first-line therapy

In the event of failure, intolerance or contraindications to first-line therapy with atezolizumab and bevacizumab, therapy with an approved tyrosine kinase inhibitor should be offered to HCC patients:

  • in Child-Pugh stage A and BCLC B or C
  • with distant metastases
  • a tumor location that cannot be controlled or resected locally.

For HCC patients with tumor progression under sorafenib in Child-Pugh stage A and ECOG 0-1, the two tyrosine kinase inhibitors regorafenib and cabozantinib or, with an alpha-fetoprotein value of ≥ 400 ng/ml, the VEGFR2 antibody ramucirumab are available.

In the event of treatment failure with lenvatinib, further tumor-specific therapy is possible. Certain recommendations cannot be made due to the currently insufficient data available. In principle, all substances that have been tested as effective in a phase III trial can be considered. According to the current status of approvals in Germany, treatment with sorafenib after lenvatinib is to be regarded as "in-label" therapy. The other approved active substances cabozantinib, ramucirumab and regorafenib are indicated after treatment with sorafenib according to the approval text.

Note: Now that several different drug-based tumor therapies are possible for hepatocellular carcinoma, treatment with a particular substance should not be continued beyond radiological progression. At the same time, the toxicity of the therapy should be closely monitored.

Immunotherapy with PD1/PDL1 inhibitors

For individual immunotherapy-naïve HCC patients with preserved liver function (Child-Pugh A stage), with distant metastases or a tumor location that cannot be controlled or resected locally and for whom no other approved therapy is available.for whom no other approved therapy is available, either an immune monotherapy with the anti-PD-1 antibodies nivolumab or pembrolizumab or a combination therapy with nivolumab and the CTLA-4 antibody ipilimumab can be offered.

Drug therapy for liver cirrhosis CHILD-Pugh B/C

For individual HCC patients in Child-Pugh stage B (up to 8 points), with distant metastases or a tumour location that cannot be controlled or resected locally and with an ECOG status of 0-1, systemic therapy with sorafenib or immunotherapy with an anti-PD-1 antibody can be offered. Systemic therapy is not recommended for HCC patients in the Child-Pugh C stage.

Prognosis

The prognosis for hepatocellular carcinoma depends on the stage of the cancer, the residual liver function and the patient's physical condition. Overall, the relative 5-year survival rate for men and women is around 15 percent. The prognosis is even less favorable only for malignant tumors of the pancreas.

For stage I tumors (single tumor, without blood vessel or lymph node involvement and without distant metastases), the relative 5-year survival is 62 percent (women) and 54 percent (men). In stage IV (lymph node involvement or distant metastases), however, only 2 percent survive the next five years. Furthermore, the prognosis correlates with the maximum tumor size, the number of tumor nodes and the underlying disease. Patients with HCC caused by alcohol-induced liver cirrhosis have a worse prognosis after curative resection than patients with HCC caused by non-alcoholic fatty liver disease, for example.

Prophylaxis

There is no reliable prophylaxis to prevent hepatocellular carcinoma. To date, there is no HCV vaccination. Dietary modifications have produced contradictory results in studies regarding their protective effect against the development of hepatocellular carcinoma.

However, a number of factors can be influenced to reduce the risk of hepatocellular carcinoma. These include

  • Hepatitis B vaccination, especially of risk groups in endemic areas
  • Limiting alcohol consumption or avoiding alcohol altogether
  • Weight reduction for non-alcoholic fatty liver hepatitis
  • careful control of diabetes
  • early causal treatment of hepatitis infections
  • Consume three or more cups of coffee a day in the case of chronic liver disease
  • early and regular treatment of underlying liver-damaging diseases, especially haemochromatosis
  • Participate in early detection of HCC, especially in the case of
    • Liver cirrhosis in Child-Pugh A and B stages
    • Patients with liver cirrhosis who are listed for liver transplantation
    • advanced liver fibrosis, regardless of the cause of the liver disease
    • chronic HCV infection
    • non-alcoholic steatohepatitis