What is liver cancer? Are all liver cancers the same disease?

Liver cancer is defined by an abnormal and uncontrolled growth of cells within the liver. These malignant cells progressively substitute the normal cells, collapsing the normal function of the liver, and invading other organs. There are two main types of liver cancer: Primary liver cancer, which appears 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 that sends the disrupted cells to the liver, where are implanted. The treatment of liver metastases 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. Focusing on primary liver cancer, there are several types according to the type of cells that are altered. The most frequent, by far, is the hepatocellular carcinoma (HCC), 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. Close

Is hepatocellular carcinoma frequent?

HCC is one of the most frequent type of cancer worldwide. Recent studies have ranked the HCC as the sixth most frequent cancer, and it is particularly common in the Sub-Saharan Africa and the Eastern. More worrisome, HCC is recognized as the third most common cause of cancer-related death. Therefore, this cancer is a priority for the Health institutions and scientific communities. Close

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

HCC appears most frequently 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 consumption, the chronic infection by hepatic virus (mainly by hepatitis B and C viruses) and the metabolic syndrome (particularly obesity and dyslipidemia). Consequently, 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, avoiding overweighting, etc.), or treating them before the liver progresses to an overt cirrhosis (for instance, antiviral therapies if the liver is chronically infected by an hepatic virus).

HCC is a silent cancer that only produces symptoms (usually tiredness, weight lost, appetite decrease, jaundice, fluid retention, intestinal bleeding, etc.) when it is too advanced, and at that point, usually there are no effective therapies. Aimed to detect this disease at an asymptomatic early stage, when treatment is feasible and effective and taking into account that the presence of cirrhosis is the most important risk factor for HCC development, all the scientific societies recommend performing surveillance for HCC by periodical abdominal ultrasound (every 6-12 months) in those cirrhotic patients in whom any treatment could be applied if an HCC is detected. Close

Is a biopsy mandatory for confirming the diagnosis of HCC?

Once a liver nodule is detected by ultrasound, a dynamic imaging technique (computed tomography or magnetic resonance) should be performed for further characterization. If this nodule displays a specific vascular profile through the different phases of the dynamic study, a conclusive HCC diagnosis can be done without the need of a biopsy. Contrarily, if the vascular pattern is not the typical, a biopsy is recommended. 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 achieve the HCC diagnosis. Close

Which is the expected outcome of HCC?

A critical step in the management of HCC is the prognosis estimation. It helps physicians to inform patients and relatives about the expected outcome and to indicate the most appropriate treatment option. The prognosis prediction of HCC is very variable and depends on several factors. The first variable to take into account is the tumor extent (number, size and extension). In that regard, small solitary tumors can be successfully treated in most cases and long-term survivals are possible. Contrarily, the presence of tumor within a vessel or outside the liver indicates an advanced stage and worse prognosis; at that point only palliative therapies are available. Second, as previously highlighted, most cases of HCC appear within an underlying chronic liver disease. Therefore, the degree of liver function reserve determines not only the treatment options, but also the outcome. Finally, it is mandatory to assess the presence of cancer-related symptoms since it indicates an advanced disease and limits the tolerance and success of several treatment approaches. Close

Is treating patients with hepatocellular carcinoma easy?

Nowadays, we have several treatment options, but the decision of which is the best is based mainly on the tumor stage, the degree of liver function impairment and the presence of cancer-related symptoms. In order to obtain the best outcome, patients should be selected carefully and the treatment applied skillfully. In view of the complexity of hepatocellular carcinoma and the many potentially useful treatments, patients diagnosed with this malignant disease should be referred to multidisciplinary teams that include hepatologists, radiologists, surgeons, pathologists, and oncologists. Close

Is surgical resection feasible?

Surgical resection is the first treatment option to be considered when we face a patient with HCC. Regrettably, since this neoplasia appears mainly associated with a chronic liver disease, resection is, in most cases, contraindicated because of impaired liver function. The best results are obtained in those patients with solitary tumors and well-preserved liver function. The outcome of surgical resection is hampered by the high rate of tumor recurrence, which may achieve 50-70% at 5 years. Disappointingly, there is not so far any proven adjuvant therapy for preventing or at least delaying the recurrence. Close

I have heard that liver transplantion is a treatment option for hepatocellular carcinoma. Is that true?

If surgical resection is not feasible because of liver function impairment or multiple nodules, the next option to be considered is liver transplantation. This approach not only allows to completely removing the tumor, but also the impaired liver. Unfortunately, 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. Close

If surgical treatments are not feasible, are there any other potential curative options?

Definitively, yes. There are several loco regional 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. The most widespread technique is the percutaneous ablation. It is based in the tumor destruction by injection of substances (for instance, ethanol or acetic acid) or by changing the intratumoral temperature (for instance, delivering heat by radiofrequency or microwave 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. In the case of radiofrequency or microwave ablation, the hospital admission is usually one day, the rate of complications is very low and the rate of success is very high. Similar to surgical resection, percutaneous ablation is hampered by a high rate of tumor recurrence. Close

Is percutaneous ablation feasible in all cases?

Regrettably percutaneous ablation is not effective in large tumors or with multiple foci. For those cases we can consider transarterial procedures. Those treatments are based on the almost exclusive arterial vascularization of the HCC compared to the mixed (arterial and venous) of the normal liver. Accordingly, those procedures allow delivering chemotherapy or radiotherapy at high doses directly into the tumor and also to selectively block the vascular feeding. The universally accepted transarterial procedure 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 TACE and we have witnessed several technical improvements associated with a better tolerance and survival. Other treatment option under active investigation is radioembolization. It is based in the intra-arterial injection of microscopic spheres containing Yttrium-90, a radioactive agent that allows a selective delivery of high dose of radioactivity within the tumor, trying to spare the surrounding liver parenchyma. This approach has shown preliminary promising results but it is not still widely accepted. Close

Is chemotherapy useful in HCC?

Several chemotherapeutical agents, alone or in combination, have been assessed in HCC. Regrettably, mainly due to the frequent association between HCC and cirrhosis, all these drugs have shown a limited efficacy and an inadmissible rate of adverse effects. Accordingly, standard chemotherapy is not recommended for HCC. Fortunately, in the last years we have been witness of important advancements in the knowledge of the disrupted molecular pathways associated with the cancer initiation and progression. This knowledge has allowed the development of 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 and widely accepted therapy in patients with advanced HCC. Furthermore, in 2016 a new drug, called Regorafenib, was approved for the treatment of hepatocellular carcinoma en second line after progression under sorafenib for those patients who are tolerant to sorafenib. There are other molecular targeted therapies under investigation in HCC, and in some of them, promising results in preliminary studies have been obtained. Consequently, 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 that will allow improving the survival and the quality of life of patients affected with HCC. Close

When standard therapies are not feasible or fail, are there other treatment options?

Yes. There is the possibility to be evaluated to enter a clinical trial. For this purpose, you must fulfill the inclusion criteria ordered by the study protocol. In this kind of studies the effect of a drug is investigated in patients. In some of these studies, two treatments are usually compared: the one that is already known as effective and the one that is under study. In other trials, new drugs are compared to placebo effect. These treatments are assigned randomly so that neither patients nor physicians choose the arm of treatment. If you join a research study, you will be watched closely and data on your case will be carefully recorded. You may receive more examinations and tests than are usually given. During the course of a study, if it is clear that a treatment is not in your best interest, you will be removed from the study and you can discuss other options with your physician. On the other hand, you may also leave the study at any time. Randomized clinical trials are mandatory to obtain the Health Authorities approval for new drugs since this kind of research is the most strict and reliable. This way, the effective dose, the efficacy, the safety and the adverse events of the study drugs, can be known. Close