Liver cancer: definition, symptoms, prognosis

Medically reviewed: 14, March 2024

Liver Cancer: An Insightful Overview

The human body hosts over five hundred distinct functions executed daily without conscious effort, many relying on organs obscured within our cores. Among them stands the unsung hero — the liver. Unseen yet vital, the liver manages detoxification, metabolism regulation, hormone production, nutrient storage, and so much more. However, when afflicted with malignancies like liver cancer, life can take a drastic turn.

This article will demystify liver cancer, equipping readers with understanding, compassion, and empowerment toward combatting this disease.

Definition and Function of the Liver

Anatomically positioned in the abdominal cavity’s superior region, partially protected by the ribcage, lies the largest solid organ inside us — the liver. Its unyielding consistency mirrors the multitude of pivotal roles it assumes each day. Structurally composed of two lobes—the left and right—this reddish-brown marvel weighs approximately three pounds in adults.

Connective tissue encases the entirety, housing blood vessels and bile ducts carrying oxygenated blood and digestion secretions, respectively.

Delving deeper into functionality, hepatocytes constitute nearly eighty percent of liver cells responsible for numerous chemical reactions involved in metabolism, protein synthesis, transformation of carbohydrates, lipids, and xenobiotic substances.

Simultaneously, Kupffer cells perform phagocytosis, eliminating potential hazards before entry into circulation. Cholangiocytes maintain bile composition ensuring optimal intestinal functioning while sinusoidal endothelial cells contribute to maintaining blood flow resistance and filtration of waste products. Lastly, stellate cells play a crucial role in extracellular matrix remodeling during injury repair.

Common Risk Factors and Causes of Liver Cancer

Regrettably, several variables may predispose individuals to liver cancer development. Preventative measures target diminishing exposure to known risks whenever feasible. Although certain causes remain beyond personal influence, gaining awareness remains imperative to prompt earlier detection and treatment initiation.

Liver Cirrhosis

Often regarded as the most significant precipitating factor, cirrhosis results from chronic liver damage leading to scarring, nodule formation, impaired structure integrity, hindered blood perfusion, and augmented regeneration susceptibility. Scarring progressively advances, culminating in fibrosis and potentially cancerous growths. Several diseases and conditions instigate cirrhosis, some avoidable. These include viral hepatitis B and C, alcohol abuse, non-alcoholic fatty liver disease, autoimmune disorders, drug toxicity, inherited metabolic disorders, among others.

Viral Hepatitis

Both hepatitis B and C viruses can induce persistent inflammation leading to DNA mutagenesis and eventual malignant conversion given prolonged infection. Vaccines exist for hepatitis B offering preventative protection, whereas no prophylactic option exists for hepatitis C necessitating cautious behavior around contaminated needles, syringes, sexual contact, or transfused blood products.

Alcohol Abuse

Excessive ethanol consumption inflicts direct cytotoxicity onto hepatocytes initiating compensatory proliferation ultimately fostering genomic alterations and neoplasm emergence after years of continued drinking. Reducing or ceasing alcohol ingestion significantly lowers associated cancer risks.

Non-Alcoholic Fatty Liver Disease (NAFLD)/Non-Alcoholic Steatohepatitis (NASH)

Rapid urbanization accompanied escalating obesity rates has led NAFLD prevalence surpass global epidemic proportions affecting nearly twenty-five percent of adult populations worldwide. Progression from steatosis (simple accumulation of triglycerides within hepatocytes) to NASH occurs due to insulin resistance, oxidative stress, mitochondrial dysfunction, gut microbiota imbalance, resulting in concurrent fibrosis aggravation raising overall liver cancer incidence.

Obesity

Beyond NALFD/NASH linkages, increased weight independently promotes tumorigenesis mechanisms involving insulin resistance, hyperglycemia, chronic inflammation, adipokine deregulation, DNA methylation patterns changes, and cell cycle modifications increasing hepatocellular carcinoma likelihood.

Genetic Predisposition

Some patients bear hereditary traits enhancing liver cancer vulnerability despite absences of environmental triggers. Conditions exhibiting inheritable propensities comprise alpha-1 antitrypsin deficiency, Wilson’s disease, porphyria cutanea tarda, glycogen storage disorders, tyrosinemia, and hereditary hemochromatosis. Certain ethnic groups exhibit higher prevalence such as Asian descent suffering disproportionately higher mortality ratios compared to Western counterparts underscores genetic contributions.

Aflatoxin Exposure

Occasionally overlooked amidst industrialized nations, dietary habits rooted in agricultural societies expose consumers primarily Southeast Asia regions to fungal contamination called aflatoxins predominantly observed in corn, peanuts, rice, spices, nuts, dried fruits causing direct hepatic DNA damage triggering molecular events favoring neoplastic expansion. Eradicating foodborne mold colonization posits effective strategies reducing circulating levels thus decreasing related cancers risk.

Different Types of Liver Cancer

Liver cancer is a complex disease with several distinct types, each having different characteristics, causes, and treatment options. This article will provide a comprehensive overview of four major liver cancer types: hepatocellular carcinoma, intrahepatic cholangiocarcinoma, angiosarcoma & hemangiosarcoma, and hepatoblastoma.

Hepatocellular Carcinoma (HCC)

• Accounting for approximately 75-85% of primary liver cancers, hepatocellular carcinoma HCC arises from hepatocytes, which are the most common cells found in the liver. HCC usually affects individuals with chronic liver diseases like cirrhosis caused by hepatitis B or C virus, alcohol consumption, nonalcoholic steatohepatitis (NASH), or exposure to certain chemicals. Symptoms may vary widely, ranging from jaundice, abdominal pain, unexplained weight loss, or fatigue.

Diagnosis typically involves imaging techniques, blood tests, and biopsy confirmation. Treatment options depend on individual patient circumstances, including tumor stage, overall health condition, and underlying liver function, and might encompass surgery, local treatments (such as ablation, embolization, or radiation therapy), systemic therapies (targeted agents or immunotherapies), or liver transplantation.

Intrahepatic Cholangiocarcinoma (ICC)

This second most prevalent form of liver cancer develops within the bile ducts inside the liver, accounting for around 10-15% of primary liver malignancies. Risk factors often overlap with those associated with HCC; however, ICC has additional associations, such as primary sclerosing cholangitis or parasitic infestations (e.g., liver flukes).

Common symptoms consist of jaundice, dark urine, light stool color, or itching skin due to biliary obstruction. Imaging studies, along with lab work measuring tumor markers (like CA 19-9), aid diagnosis, which generally requires histological confirmation.

Curative approaches primarily rely on surgical resection when feasible or liver transplantation, whereas palliative measures incorporate chemotherapy, targeted drugs, or radiation therapy targeting both local progression and metastasis management.

Angiosarcoma & Hemangiosarcoma

These rare forms of liver cancer stem from endothelial cells lining blood vessels. Angiosarcoma originates in veins, while hemangiosarcoma emerges from arteries. Together, they account for less than 1% of primary liver malignancies. Rapid growth leads to nonspecific symptoms like abdominal discomfort, distension, or constitutional complaints (fever, weakness, or weight loss).

Unfortunately, diagnosis frequently occurs late because early signs remain subtle or absent. Computed tomography (CT) scans and magnetic resonance imaging (MRI) examinations facilitate identification, although biopsy remains indispensable for definitive assessment.

Due to aggressive behavior, complete surgical removal represents the sole chance for cure unless widespread dissemination mandates chemotherapy or palliative strategies aimed at symptom relief.

Hepatoblastoma

As the most frequent pediatric liver cancer, hepatoblastoma predominantly impacts children under five years old. Its origins trace back to embryonal liver tissue during fetal development. Presenting indicators tend to manifest as abdominal masses discovered either accidentally or following parental concerns about abnormal belly appearances.

Serum alpha-fetoprotein (AFP) levels rise significantly in nearly two-thirds of affected patients, serving as a valuable diagnostic marker. Ultrasound, CT scan, or MRI determine tumor extent, helping establish therapeutic plans centered around surgical excision supplemented by neoadjuvant or adjuvant chemotherapy regimens tailored to individual risk stratifications based on clinical trials’ results. Radiation therapy plays occasional roles depending on specific cases.

Recognizing the Signs: A Comprehensive Guide to Symptoms of Liver Cancer

The liver, located in the upper right quadrant of our abdomen, performs vital functions maintaining optimal well-being. However, liver cancer poses significant challenges globally, necessitating understanding and identifying possible warning signals promptly.

With varying presentations among adults, being knowledgeable about general symptoms becomes crucial for timely intervention and improved outcomes. Diving deep into the realm of liver cancer, we focus here on unmasking its varied manifestations to raise consciousness, enabling decisive action against concerning symptoms.

General Symptoms of Liver Cancer

Early detection elevates survival rates substantially across numerous solid organ cancers, including liver malignancies. Often asymptomatic in initial stages, some individuals experience vague signals potentially linked to emerging hepatic lesions requiring investigation. Such obscure alerts pose difficulties for healthcare providers in attributing them directly to liver cancer, resulting in delays between first indication occurrence and accurate diagnoses. Consequently, familiarity with the broad spectrum of signs helps equip concerned parties toward rapid consultation, enhancing prospects for favorable interventions.

Common Symptoms

While no universal checklist guarantees discovery of incipient liver tumors, there exist prevailing red flags indicating probable maladies impacting the largest internal accessory gland in humans. Some widespread indications comprise:

• Unintentional Weight Loss:

Progressive shedding of pounds without dietary modifications suggests altered physiology possibly triggered by occult illness. Although countless conditions precipitate involuntary slimming down, persistent unexplained decreases warrant evaluation, particularly focusing on visceral organs susceptible to discreet structural derangements.

• Fatigue:

Prolonged lethargy ranks high among frequent complaints reported worldwide. Similar to incidental body mass reductions, exhaustion accompanies various disorders, impeding straightforward linkage to subsurface liver cancers. Nevertheless, profound, prolonged weariness prompts rigorous exploration.

• Abdominal Discomfort or Distention:

Epigastric region soreness or swelling acts as another ubiquitous complaint necessitating thorough scrutiny. Accurate interpretation demands astute clinicians capable of distinguishing innocuous entities from severe intrabdominal insults. Pain escalation points towards likely organic etiologies requiring radiographic surveillance, serologic assessments, and multidisciplinary collaboration.

Specialized Manifestations

Beyond diffuse clues, peculiar bodily reactions offer insights hinting specifically at impending liver pathologies. These particular expressions entail:

• Jaundiced Appearance:

Elevated bilirubin causing yellowish pigmentation warrants consideration as obstructive cholestatic mechanisms advance via expanding central divider injuries sustained at microvascular levels. Once auscultatory findings support suspicion, urgent verification methods confirm structural barriers ultimately guiding prospective remedial tactics.

• Altered Bowel Movements:

Descending colon contents reflectupstream milieu influences, translating into characteristic variations of stool caliber, texture, consistency, and hue. Thus, pale fecal matter evokes suspicions of concealed icterus engendered by predisposing factors promoting stasis within biliary tracts consequential to developing neoplastic occlusive processes.

• Enhanced Appetite for Proteinaceous Foodstuffs:

Paraneoplastic phenomena unfolding in association with burgeoning epithelial tumefactions exert fascinating effects eluding conventional wisdom frameworks. One remarkable illustration embodied in Ace synthesis dysregulation contributes to pathologically augmented cravings for proteinaceous food groups heralding aberrant biological developments demanding subsequent invasive diagnostics.

Treatment options for Liver Cancer

Chemo for Liver Cancer

Although many anticancer compounds populate contemporary pharmacopeias, select prominent ones exhibit exceptional efficacy versus liver malignancies. Two key classes featuring regularly are:

• Anthracyclines: Agents derived from Streptomyces bacteria wield potent cytotoxicity targeting DNA integrity. Chief representatives encompass doxorubicin and epirubicin.
• Microtubule Inhibitors: Targeting tubulin proteins integral to cell division, taxanes (e.g., paclitaxel) and vinca alkaloids (e.g., vinblastine) disrupt mitotic spindle assembly impairing uncontrolled multiplication.

Impacts of Systemic Therapy Upon Liver Tumors

Chemotherapy works against cancer cells in two ways: first, by killing the dividing cells directly, and second, by changing how our immune system responds to cancer. Here’s what happens when chemotherapy goes to work:

1. Stopping cell division: Chemotherapy targets fast-dividing cells, like cancer cells, and stops them from multiplying. It does this by halting the cells in specific sensitive phases of their division process.
2. Triggering cell death: Chemotherapy damages cancer cells, causing them to self-destruct through a process called apoptosis. This helps clean up damaged and harmful cells in the body.
3. Boosting the immune system: During treatment, chemotherapy triggers damage signals in dying cancer cells. This sends messages to our immune system, alerting it to start attacking remaining cancer cells.

Managing Chemotherapy’s Good and Bad Effects

While chemotherapy kills cancer cells, it can sometimes affect healthy cells too, causing unwanted side effects. These problems may include nausea, hair loss, lowered counts of white and red blood cells, heart damage, nerve troubles, numbing or tingling feelings, and increased chances of getting an infection. Skilled doctors carefully monitor patients and give appropriate supportive care to minimize these issues while allowing the beneficial parts of chemotherapy to continue working.

Targeted Therapy in Liver Cancer Treatment: An In-depth Analysis

Targeted therapy refers to a specialized approach in treating cancers where drugs or other substances target specific cellular changes (mutations) found only in cancer cells. These medications block the growth and spread of tumors by interfering with specific receptors, proteins, or genes involved in the growth, progression, and metastasis of malignant cells. By focusing specifically on cancerous tissues rather than healthy ones, targeted therapy often results in fewer side effects compared to conventional chemotherapy or radiation.

Types of Targeted Therapy Available for Liver Cancer

In liver cancer, several types of targeted therapies have been approved by regulatory authorities based on proven clinical benefits. Some common options include:

1. Sorafenib (Nexavar): Approved by the U.S. Food and Drug Administration (FDA) since 2007, sorafenib inhibits several protein kinases implicated in angiogenesis and cancer cell proliferation, thereby slowing down disease progression.
2. Lenvatinib (Lenvima): Also an oral multi-kinase inhibitor, lenvatinib demonstrates non-inferiority to sorafenib in overall survival rates for unresectable hepatocellular carcinoma patients. It targets similar molecular pathways as sorafenib but shows superior response rates.
3. Regorafenib (Stivarga): Another oral multikinase inhibitor, regorafenib improves overall survival in patients who have previously received sorafenib. It works similarly to sorafenib but has added activity against additional enzymes associated with resistance mechanisms.
4. Cabozantinib (Cabometyx): Indicated for advanced HCC after prior systemic therapy, cabozantinib is a tyrosine kinase inhibitor that acts on several key signaling molecules contributing to tumor growth and invasiveness.

Mechanisms of Action of Targeted Therapies

These targeted therapies work primarily by blocking crucial signaling cascades required for tumor initiation, promotion, invasion, and metastasis. They interfere with vital biological functions such as angiogenesis (the formation of new blood vessels supporting tumor growth), cell cycle regulation, apoptosis (programmed cell death), and immune evasion strategies employed by malignancies.

Specifically, they disrupt vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), c-Kit, RET, and RAF family kinases, leading to reduced cancer cell viability and impaired tumor microenvironment interactions.

Comparative Efficacy vs Side Effects

Compared to traditional cytotoxic agents used in chemotherapy, targeted therapies generally offer improved therapeutic indices due to their selectivity towards neoplastic cells. Nonetheless, some common side effects observed across different classes of targeted therapies may include fatigue, hypertension, hand-foot skin reactions, diarrhea, and decreased appetite. Despite these manageable toxicities, targeted therapies have shown significant improvements in patient outcomes, extending overall survival and offering better quality of life compared to older modalities.

Liver Cancer Prognosis: What You Should Know About Each Stage

When dealing with liver cancer, knowing the meaning of “prognosis” and understanding its connection to the different stages of the illness are essential. Learning about the four main stages of liver cancer will help you grasp the implications of each stage, know which treatment plan suits best, evaluate possibilities for recovery, and realize why prevention matters more than ever.

Early Stage Liver Cancer (BCLC 0 and A)

At this stage, the liver cancer affects only one spot in the organ. Doctors may recommend removing or eliminating the affected tissue through operations like surgical resection, ablation techniques (using radiofrequency waves or ethanol injection), or liver transplantation. Successfully treated patients at this stage have a good chance of living for another five years (survival rate ranging from 28% to 55%). Post-treatment observation and regular check-ups play a crucial role in catching recurrences early.

Intermediate Stage Liver Cancer (BCLC B)

Progressing to this stage brings satellite nodules close to the original tumor. Although still eligible for removal, completely curing the cancer becomes less likely because of scattered foci outside the primary area. Treatments like chemoembolization, radioembolization, microwave ablation, or stereotactic body radiotherapy try to limit tumor growth and maintain optimal functioning. Anticipate median survivals around two years, given proper supervision to trace the disease’s development closely.

Advanced Stage Liver Cancer (BCLC C)

Mainly defined by extensive portal vein clots or external metastasis, this stage presents great difficulty due to reduced opportunity for intensive surgeries. Turning to systemic therapies, like immunotherapeutic antibodies combined with tyrosine kinase inhibitors, holds merit when tackling far-reaching affliction. Current estimates indicate approximately ten more months of life expectancy with these methods. Continuous exploration aims to significantly improve positive results, prolonging life and promoting enhanced longevity.

Terminal Stage Liver Cancer (BCLC D)

Unfortunately, reaching this last milestone implies severe decline in general wellness. Limited solutions remain aside from relieving suffering and retaining dignity through compassionate care provided by palliative services and hospices. Devoid of a cure, attentive attention must go towards easing burden and stress for everyone touched by this tragic circumstance. Life span averages merely three months, driving home the necessity of timely discovery and protective initiatives.

Liver Cancer: Essential Knowledge Points to Remember

Navigating information about liver cancer can feel overwhelming. Our goal here is to demystify complex concepts and provide you with clear key points worth remembering. Arming yourself with this knowledge empowers you to actively participate in shared decision-making discussions concerning diagnostic procedures and possible treatment plans.

There exist two major kinds of primary liver cancer: hepatocellular carcinoma (HCC), stemming from hepatocytes (major liver cells making up roughly 80% of the liver’s mass), and cholangiocarcinoma arising within bile duct epithelial cells constituting the remaining portion of the liver. Occasionally, hybrid tumors combine elements of both categories, known collectively as mixed hepatocellular-cholangiocarcinomas.

Common causes behind developing primary liver cancer comprise chronic viral hepatitis infections (primarily HBV and HCV), excessive alcohol consumption, exposure to certain chemicals and environmental pollutants, obesity, diabetes, and inherited genetic disorders impacting the liver, such as hemochromatosis and Wilson’s disease.

Concerning symptomatology, watch out for unexplained weight loss, jaundice, lack of appetite, fatigue, nausea, vomiting, and discomfort or pain felt in the upper right abdomen region. If detected earlier, there exists a higher likelihood of successfully managing liver cancer.

Doctors utilize staging systems—such as Barcelona Clinic Liver Cancer (BCLC), Okuda, Japan Integrated Staging (JIS), Chinese University Prognostic Index (CUPI), and Tokyo Score—to estimate prognosis and tailored treatment planning depending on severity and extent of the disease. Your healthcare team will guide you through interpretation and relevance of each system applicable to your situation.

Typically, imaging tests like ultrasound, CT scans, and MRIs serve as initial screening methods. Subsequent confirmatory evaluations involve biopsying suspicious tissue samples or applying liquid biopsy techniques measuring circulating tumor DNA, miRNA, or extracellular vesicles in bodily fluids to identify molecular alterations indicative of liver cancer presence.

Systemic therapies reach entire bodies to combat distant metastases and widely dispersed lesions insusceptible to direct intervention. Commonly prescribed agents include small-molecule inhibitors (e.g., sunitinib, sorafenib, lenvatinib), monoclonal antibodies (e.g., atezolizumab, ramucirumab, durvalumab plus tremelimumab combinations), adoptive cell transfer (ACT), or immune checkpoint inhibition therapy. Recent breakthroughs reveal notable success rates harnessing genetically modified lymphocytes programmed to recognize and eliminate malignant cells expressing specific surface markers expressed uniquely by them.