What is liver cancer?

Liver cancer is defined by an abnormal and uncontrolled growth of cells within the liver. These altered cells progressively substitute the normal cells, collapsing the normal function of the liver, and invading other organs. These events irremediably lead to the death of the patients affected from this disease. We should distinguish liver cancer from benign tumors, that are also the result of an altered cellular growth, but they lack the invasiveness capacities of the malignant tumors (cancer). Therefore, the prognosis of benign tumors is excellent and in the majority of cases there is no need of treating them.

A relative has been diagnosed with liver metastases. Is it liver cancer?

Briefly, there are two main types of liver cancer: Primary liver cancer, which appear from the cells that are normally located in the liver, and secondary liver cancer (also known as metastases), that is a cancer originated in other part of the body (in the lungs, breasts or in the colon, for instance) that sends the diseased cells to the liver, where are implanted. The treatment of this secondary liver cancer depends on the type of primary cancer from which is originated, and is mainly based in the use of pharmaceutical drugs commonly known as chemotherapy. We will focus our information on the primary liver cancer. There are several types of primary liver cancer according to the type of cells that are altered. The most frequent, by far, is the hepatocellular carcinoma (HCC), which is a cancer derived from the main cell of the liver called hepatocyte. There are other types of primary liver cancer such as intrahepatic cholangiocarcinoma (derived from the biliary cells), sarcomas, etc., that should also be taken into account.

Is primary liver cancer frequent?

Primary liver cancer is a very common cancer worldwide. Recent studies ranked the primary liver cancer as the sixth most frequent and it is particularly common in the Eastern and Sub-Saharian Africa. Therefore, this cancer is a priority for the Health institutions and scientific communities.

Is there any risk factor for its appearance? How can we prevent it?

HCC appears mainly in patients with a chronic liver disease, particularly when this liver disease is advanced and causes cirrhosis. There are several causes of liver disease, but the most important are the alcohol abuse and the chronic infection by hepatic virus (mainly by hepatitis B and C viruses). Accordingly, the most effective way to prevent the development of HCC is avoiding those agents that are able to damage the liver (for instance, universal vaccination for preventing the infection by hepatitis B virus, avoiding excessive alcohol consumption, etc.), or treating them eagerly before the liver develops cirrhosis (for instance, antiviral therapies if the liver is chronically infected by an hepatic virus).

Which kind of symptoms is associated with the development of HCC?

HCC produces symptoms when it is too advanced and at that point, usually there are no effective therapies. The most frequent symptoms are tiredness, weight lost, appetite decrease, and signs of liver failure such as jaundice, fluid retention, intestinal bleeding, etc.

If HCC is usually asymptomatic at the beginning, how can we detect it at early stages?

As we have pointed out, the presence of cirrhosis is the most important risk factor for HCC development. For that reason, all the scientific societies recommend performing a periodical abdominal ultrasound (every 6-12 months) in those cirrhotic patients in whom any treatment could be applied if an HCC is detected. The aim of this surveillance program is detecting the disease at early stages, when treatment is feasible and effective.

How can HCC be diagnosed?

Once a suspicious liver nodule is detected by ultrasound, it is recommended to perform a dynamic imaging technique (computed tomography or magnetic resonance) for further characterization. If this nodule displays a specific vascular profile through the different phases of the dynamic study, the HCC diagnosis can be confidently done without the need of a biopsy. Contrarily, if the vascular pattern is not the typical, the only way to confirm the diagnosis of HCC is by obtaining a biopsy. There is an active research in tumor markers that could help physicians to diagnose the disease at a very early stage, when imaging techniques and pathological assessment are unable to confidently perform the HCC diagnosis.

I have heard that the hepatocellular carcinoma is a cancer with a very bad prognosis. Is that true?

The prognosis of HCC is very variable and depends on several factors. First, the number, size and extension of the tumor. In that regard, the presence of tumor within a vessel or outside the liver indicates an advanced stage and poor prognosis; at that point only palliative therapies are available. Contrarily, small solitary tumors can be successfully treated in most cases and long-term survivals are possible.  Second, we have to keep in mind that in most cases HCC appears within an underlying chronic liver disease. Therefore, the degree of liver function reserve determines not only the treatment options, but also the outcome. Finally, the presence of symptoms indicates an advanced disease and limits the tolerance and success of several treatment approaches. As a summary, the prognosis of this cancer is very wide and your physician can inform you about the expectation and treatment possibilities.

Is surgery useful for HCC?

As stated previously, there are several treatment options, but the decision of which is the best is based mainly on the tumor stage and the degree of liver function impairment.  In the case of HCC, the first option is surgical resection. However, this approach is contraindicated in those patients with decompensated cirrhosis and the best outcome is obtained in those patients with solitary tumors and well-preserved liver function. If surgical resection is not feasible, the next option to be considered is liver transplantation. This approach not only allows to completely remove the tumor, but also the impaired liver. Lamentably, the scarcity of donors and the potential risk of tumor recurrence after liver transplantation determine that only those candidates with the best-expected outcome should be enlisted. In that regard, liver transplantation is contraindicated in those cases with vascular invasion or extrahepatic spread and in most centers there are a pre-established limits according to the size and number of nodules. In addition, advanced age and associated diseases may also constitute a contraindication for liver transplantation.

If surgery is not indicated, are there any other effective options?

Definitively, yes. There are several locoregional approaches that are designed for efficiently destroying the tumor without affecting the surrounding liver parenchyma. These treatments are potentially curative and allow increasing the survival.  One modality is the percutaneus ablation. It is based in the injection of substances (for instance, ethanol or acetic acid) or the change of the intratumoral temperature (for instance, delivering heat by radiofrequency or freezing the tumor by cryotherapy) using a device introduced through the skin by the guidance of an imaging technique, usually ultrasonography. This treatment modality is recommended in patients with small tumors in whom surgical treatments are not feasible or during the waiting time for liver transplantation. Regrettably, these treatments are not effective in large tumors or with multiple foci. Another strategy is the transarterial procedures. These treatments are based on the almost exclusive arterial vascularization of the HCC compared to the mixed (arterial and venous) of the normal liver. These procedures allow delivering chemotherapy or radiotherapy at high doses directly into the tumor and also to selectively block the vascular feeding. The most frequently transarterial therapy used worldwide is the transarterial chemoembolization (also known as TACE) and is habitually used in large tumors and/or multifocal. In the last years, there has been an active research in the field of locoregional therapies and they have become a cornerstone treatment modality for this disease.

Is chemotherapy useful in HCC?

Several chemotherapeutical agents, alone or in combination, have been evaluated in HCC. Regrettably, all these studies have shown a limited efficacy and an inadmissible rate of side effects, mainly due to the frequent association between HCC and cirrhosis. Accordingly, standard chemotherapy is not recommended for HCC. Luckily, in the last years, great advancements have been done in the knowledge of the disrupted molecular pathways associated with the cancer initiation and progression. These findings have allowed to design new agents that specifically and selectively block the altered pathways, minimizing the frequent side effects associated with conventional therapies. Among them, the only one that up to date has shown benefits in term of survival is sorafenib, an oral available multikinase inhibitor that acts mainly inhibiting the tumor proliferation and the formation of new vessels, freezing the tumor growth. The positive results obtained with sorafenib in several clinical trials have justified that this agent has become the standard therapy in patients with advanced HCC. There are other molecular targeted therapies under investigation in HCC, and in some of them, promising preliminary results have been obtained. Accordingly, it is highly recommended to participate in clinical trials that evaluate these novel agents. Undoubtedly, in the next years further treatment advancements will be in place, allowing to increase the survival and the quality of life of patients affected with HCC.

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