We searched Medline, Embase, and the Cochrane Library (from January, 2000, to November, 2011) with the terms “hepatocellular carcinoma”, “liver cancer”, and “primary liver carcinoma”. We also searched and reviewed the reference lists of retrieved publications for other relevant papers. We only considered papers published in English and Spanish. We selected publications largely from the past 5 years, but we did not exclude commonly referenced and highly regarded older publications.
SeminarHepatocellular carcinoma
Introduction
Hepatocellular carcinoma is the sixth most common neoplasm and the third most frequent cause of cancer death.1 More than 700 000 cases of this malignant disease were diagnosed in 2008, with an age-adjusted worldwide incidence of 16 cases per 100 000 inhabitants.1 Hepatocellular carcinoma is the leading cause of death among patients with cirrhosis.2 Here, we update our 2003 Lancet Seminar3 to include major advances in prevention, detection, diagnosis, and treatment that have happened since then.
Section snippets
Risk factors and prevention
In most cases, hepatocellular carcinoma develops within an established background of chronic liver disease (70–90% of all patients).4 The worldwide heterogeneous incidence reflects variations in the main risk factors (table 1).1, 5 Most cases of hepatocellular carcinoma (80%) arise in eastern Asia and sub-Saharan Africa, where the dominant risk factor is chronic infection with hepatitis B virus (HBV), together with exposure to aflatoxin B1. By contrast, in North America, Europe, and Japan,
Molecular pathogenesis
Hepatocarcinogenesis is a complex multistep process in which many signalling cascades are altered, leading to a heterogeneous molecular profile.28, 29 The main mutations include the tumour suppressor gene TP53 (present in about 25–40% of cancers, depending on tumour stage), and the gene for β catenin, CTNNB1 (about 25%, predominantly in HCV-related hepatocellular carcinoma). Other mutations are less frequent. Chromosomal amplifications (1q, 6p, 8q, 17q, and 20q) and deletions (4q, 8p, 11q, 13q,
Molecular classification of hepatocellular carcinoma
Molecular profiling is relevant in cancers such as those of breast, lung, colon, and melanoma, and in some instances molecular subclasses and response to treatment are linked—eg, amplification of ERBB2 and response to trastuzumab. Outcome prediction depends on both tumour profiling (defining Wnt subclass, tumour growth factor β [TGF β], and epithelial cell adhesion molecule [EPCAM] and inflammation class)29, 35 and gene expression of adjacent non-tumoral tissue.36, 37 Transfer of this
Surveillance and diagnosis
Surveillance for hepatocellular carcinoma aims to reduce disease-related mortality. In uncontrolled studies, survival seemed to be improved with surveillance but these studies are affected by biases of lead time (the apparent improvement in survival that comes from the diagnosis being made early in the course of a disease) and length time (the apparent improvement in survival that arises because surveillance preferentially detects slow-growing cancers).38 One randomised controlled trial of
Staging and prognosis assessment
Assessment of prognosis is a crucial step in management of patients with hepatocellular carcinoma. Years ago, most affected individuals were diagnosed at an advanced symptomatic stage, when treatment was not feasible and short-term prognosis was dismal. Diagnosis has now advanced, and effective early treatment of patients is associated with median survival beyond 5 years. Any attempt to assess prognosis should account for tumour stage, degree of liver function impairment, and presence of
Treatment
For treatment to be most effective, patients should be selected carefully and the treatment applied skilfully. 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. By contrast with other highly prevalent cancers, the level of evidence for most therapeutic options for
Future perspectives
Treatment of hepatocellular carcinoma has changed greatly within the past decade and has become a major area for research. Patients diagnosed with this malignant disease can benefit from effective options that will improve their survival, whatever the evolutionary stage at which they have been diagnosed. Obviously, improvement in several areas is still needed. Recurrence after ablation or resection is a major drawback, and effective preventive agents are needed. Also, progression after
Search strategy and selection criteria
References (127)
- et al.
Hepatocellular carcinoma
Lancet
(2003) - et al.
Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality
Gastroenterology
(2006) - et al.
Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma
Gastroenterology
(2004) - et al.
Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma
J Hepatol
(2005) - et al.
Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22 707 men in Taiwan
Lancet
(1981) - et al.
Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”?
Hepatology
(2001) - et al.
Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review
J Hepatol
(2010) - et al.
Hepatocellular carcinoma in cirrhosis: incidence and risk factors
Gastroenterology
(2004) - et al.
Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis
Clin Gastroenterol Hepatol
(2010) - et al.
Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C
Gastroenterology
(2011)
Angiogenesis in liver disease
J Hepatol
Principles of cancer screening: lessons from history and study design issues
Semin Oncol
Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis
Am J Med
Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis
Am J Gastroenterol
Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status
J Hepatol
Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma
Gastroenterology
Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma
Gastroenterology
Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival
J Hepatol
Optimization of imaging diagnosis of 1-2 cm hepatocellular carcinoma: an analysis of diagnostic performance and resource utilization
J Hepatol
A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis
Gastroenterology
A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System
J Hepatol
Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival
Hepatology
Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial
Lancet Oncol
The evolving role of radiation therapy in hepatocellular carcinoma
Cancer Radiother
Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes
Gastroenterology
Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies
J Hepatol
Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma
Gastroenterology
A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma
Gastroenterology
Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients
Gastroenterology
Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics
J Hepatol
Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy
J Hepatol
Adjuvant interferon therapy after curative therapy for hepatocellular carcinoma (HCC): a meta-regression approach
J Hepatol
Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis
Hepatology
Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference
J Hepatol
Waiting list removal rates among patients with chronic and malignant liver diseases
Am J Transplant
A model to predict survival in patients with end-stage liver disease
Hepatology
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Int J Cancer
Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection
Aliment Pharmacol Ther
Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis
Semin Liver Dis
Trends in mortality from hepatocellular carcinoma in Europe, 1980–2004
Hepatology
Hepatocellular carcinoma
N Engl J Med
A Joinpoint regression analysis of long-term trends in cancer mortality in Japan (1958–2004)
Int J Cancer
Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression
Gastroenterology
Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults
N Engl J Med
Coffee drinking and hepatocellular carcinoma: an update
Hepatology
Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level
JAMA
Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death
Gastroenterology
Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children
N Engl J Med
Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study
Hepatology
Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan
Ann Intern Med
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