Liver cirrhosis is a chronic disease deriving from a chronic inflammatory and/or degenerative process caused by several pathologies that lead to a morpho-functional deterioration of the liver during the years. It can progress to more advanced forms that affect the whole organism with the onset of decompensation and complications.
The term cirrhosis derives from a Greek words “kirrhòs” which means "yellowish", and “-osis” which means "condition", indicating precisely the appearance that the liver in the advanced stage of the disease.
In the progression of liver damage to cirrhosis, healthy liver tissue is replaced by fibrotic tissue which is associated with liver malfunction. It slows down the liver's ability to process nutrients, hormones, drugs and natural toxins. The production of proteins and other substances produced by the liver is also reduced.
Some of its main triggers are alcohol abuse, chronic viral hepatitis (HBV, HCV and HDV) and metabolic disease. In particular, an increase in the metabolic component is expected to be one of the causes of cirrhosis in the next few years. This is mainly due to unhealthy lifestyle and less-than-optimum nutrition that can lead to the development of non-alcoholic steatohepatitis or non-alcoholic fatty liver disease (NASH/NAFLD). The worsening of the disease over the years can lead to the progression of inflammatory and oxidative states, resulting in cirrhosis.
However, it should be noted that chronic liver diseases are preventable by a healthy lifestyle (e.g. reducing alcohol consumption and by having a balanced diet) controllable, or treatable. Therefore, liver cirrhosis can be effectively delayed or even blocked. Effective and safe drugs with direct antiviral action capable of eliminating the hepatitis C virus in over 80% of patients are available. However, treatment depends on the caused and stage of the cirrhosis.
In Italy, there are about 30-60 cases/year of cirrhosis per 100,000 inhabitants. Currently, it is estimated that there are 200-250,000 individuals affected by cirrhosis. According to the 2016 Italian multicentres recommendations proposed by several major Italian hepatology societies (AISF, AIOM, IT-IHPBA, SIC, SIRM, SITO), high-risk cirrhotic patients should be included in surveillance programs. According to the AISF EASL (European Association for the Study of the Liver) guidelines, this surveillance should be performed every six month for the majority of patients at risk, can be by ultrasound alone and ultrasound and Alpha fetoprotein(AFP) measurement that increases the sensitivity for 7-8%, or with CT (computed tomography,) and MRI (magnetic resonance imaging), if there are difficulties in performing the ultrasound.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer. It represents the sixth cancer by incidence with over 900,000 diagnosed cases every year, worldwide, with majority of cases (2/3) are in males (https://gco.iarc.fr/).
Among European countries, Italy ranks the first or the number of newly diagnosed liver cancer cases every year (https://gco.iarc.fr/) registering about 11,700 new cases and 9700 deaths/year. From epidemiological data of the Italian Association for the study of the liver, 90.4% of tumors arise in patients with cirrhosis, which is correlated with various factors of different origins. The main risk factor is still the chronic infection of hepatitis C virus (49%), despite the presence of new direct antiviral (DAA Direct Antiviral Agents ) able to eliminate the virus. In these patients, prolonged liver damage is developed in years, also without high viral load. The percentage of patients with cancer derived from alcoholic cirrhosis remains stable (19%), while in contrast, recently, liver cancer case is increased as the effect of "Nonalcoholic Fatty Liver Disease" (NAFLD). It is expected to become the leading cause of liver cancer in future.
In many cases, during early stages, liver cancer may be asymptomatic, thus periodic monitoring of patients with cirrhosis is required. During its progression, some pain in the abdominal area, weight loss, ascites, dyspepsia, abdominal swelling, anorexia, asthenia, hepatomagaly, fever up to the rarest acute abdomen and dyspnoea, might be noticed. Liver cancer is mainly diagnosed with imaging techniques (ultrasound, computed tomography, magnetic resonance imaging), since it is one of the few tumors in which biopsy is often not recommended.
Early liver cancer diagnosis allows clinicians to intervene with curative treatment to completely eliminate the malignant nodule, such as liver transplantation or liver resection. However, these treatments need a proper status of both liver and patient. Another valid treatment alternative for early stage is radiofrequency thermal ablation which uses heat to destroy the tumor mass. Some other treatments such as radiotherapy, radioembolization, laser ablation, alcoholization, can be also opted. One of the most common treatments, also for intermediate stages, is chemoembolization. It uses a catheter inserted through a blood vessel to release chemotherapy drugs targeting the cancer nodule. The simultaneous closure of the efferent vessels guarantees the permanence of the drug for a prolonged period so that it can be absorbed by the tumor cells. At the same time, it blocks the blood flow towards the tumor, and therefore limits nutrients and oxygen. In this way, it induces both ischemic necrosis and drug-derived cytotoxicity, reaching to a concentration 40 times higher in the tumor than in the surrounding untreated area.
The video showes an example of chemioembolization procedure.
The video showes an example of transarterial chemoembolization (TACE). The insertion of a small catheters through a blood vessel, a chemotherapeutic drug is released in proximity of the nodule. The drug is delivered through microspheres of biocompatible materials.
For liver cancer in advanced stages, there are latest generation targeted-therapy drugs that block tumor proliferation. In recent years, research in the field of cancer has focused both on the identification of molecules for early diagnosis and on the development of specific molecular target drugs to be adapted to the individual patient, in order to favour a personalized therapy rather than a generalized medicine.
Indicazioni pratiche per un modello di gestione condivisa tra Medico di Medicina Generale e Specialista Epatologo del paziente con cirrosi epatica ASSOCIAZIONE ITALIANA PER LO STUDIO DEL FEGATO
Raccomandazioni multisocietarie italiana (AISF, AIOM, IT-IHPBA, SIC, SIRM, SITO) per la gestione clinica integrata del paziente con epatocarcinoma.
Figure 1. Modified from: BruceBlaus (Adert traduzione), CC BY-SA 4.0 , via Wikimedia Commons
Figure 2. Amadalvarez, CC BY-SA 4.0 , via Wikimedia Commons
Figure 4. Signimu, CC BY-SA 3.0 , via Wikimedia Commons