Hepatocellular carcinoma in primary biliary cirrhosis: Detection by α-fetoprotein estimation
Abstract
Serial estimations of serum α-fetoprotein in 130 white patients from the United Kingdom with primary biliary cirrhosis who were followed for periods of 1–52 mo revealed 5 cases of hepatocellular carcinoma; all were subsequently confirmed histologically. At the time α-fetoprotein was first noted to be elevated, none had signs or symptoms of tumor development. Of the 52 patients who died during the follow-up period, hepatocellular carcinoma was the cause of death in 3 (33%) of the 9 men, and 2 (5%) of the 43 women. Allowing for the marked predominance of women among patients with primary biliary cirrhosis, hepatocellular carcinoma may be no less frequent in primary biliary cirrhosis than in other types of cirrhosis.
References (13)
- S Sherlock
Primary biliary cirrhosis (chronic intrahepatic obstructive jaundice)
Gastroenterology
(1959) - DT Purtilo et al.
Cirrhosis and hepatoina occurring at Boston City Hospital (1917–1968)
Cancer
(1973) - WD Stone et al.
The natural history of cirrhosis
Q J Med
(1968) - HA Edmondson et al.
Neoplasms of the liver
- N Krasner et al.
Hepatocellular carcinoma in primary biliary cirrhosis: report of four cases
Gut
(1979) - J Roll et al.
The prognostic importance of clinical and histological features in asymptomatic and symptomatic primary biliary cirrhosis
N Engl J Med
(1983)
Cited by (80)
Hepatocellular carcinoma
2018, Practical Hepatic Pathology: A Diagnostic Approach: Second EditionLong-term Outcomes of Patients With Primary Biliary Cirrhosis and Hepatocellular Carcinoma
2012, Clinical Gastroenterology and HepatologyHepatocellular carcinoma (HCC) is an aggressive tumor that frequently develops in patients with primary biliary cirrhosis (PBC). We determined the mortality of patients with PBC who develop HCC, and which interventions (surgery, radiofrequency ablation, chemoembolization, alcohol injection, or transplantation) increase survival times. We investigated whether the Milan criteria predict outcomes of these patients and are effective in selection for liver transplantation.
We evaluated data from 38 patients who had a confirmed diagnosis of PBC and HCC between March 1993 and February 2011. Patients were grouped based on whether or not they met the Milan criteria. Survival was assessed using the Kaplan–Meier analysis.
Eighteen of the 38 patients (47.3%) died during the follow-up period; 49.4% survived for 5 years and 31.7% survived for 10 years. Thirty-five patients (92.0%) underwent one or a combination of interventions. Liver transplantation improved survival (risk ratio, 0.06; P < .0001), whereas surgery approached significance in causing deterioration (risk ratio, 2.87; P = .07). Mortality did not appear to be affected by meeting the Milan criteria (P = .84).
Five- and 10-year survival times for patients with PBC who developed HCC were 49.4% and 31.7%, respectively. Patients who meet the Milan criteria receive liver transplantation as often as those who do not; we did not observe a difference in survival time between groups. Patients with PBC who develop HCC appear to benefit from aggressive therapies.
Hepatocellular Carcinoma
2011, Practical Hepatic Pathology: A Diagnostic Approach A Volume in the Pattern Recognition Series, Expert Consult: Online and PrintPathogenesis of hepatitis B virus infection
2010, Pathologie BiologieThe adaptive immune response is thought to be responsible for viral clearance and disease pathogenesis during hepatitis B virus infection. It is generally acknowledged that the humoral antibody response contributes to the clearance of circulating virus particles and the prevention of viral spread within the host while the cellular immune response eliminates infected cells. The T cell response to the hepatitis B virus (HBV) is vigorous, polyclonal and multispecific in acutely infected patients who successfully clear the virus and relatively weak and narrowly focussed in chronically infected patients, suggesting that clearance of HBV is T cell dependent. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV has been proven by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBsAg specific CTL into HBV transgenic mice. Remarkably, the CTLs also purge HBV replicative intermediates from the liver by secreting type 1 inflammatory cytokines thereby limiting virus spread to uninfected cells and reducing the degree of immunopathology required to terminate the infection. Persistent HBV infection is characterized by a weak adaptive immune response, thought to be due to inefficient CD4+ T cell priming early in the infection and subsequent development of a quantitatively and qualitatively ineffective CD8+ T cell response. Other factors that could contribute to viral persistence are immunological tolerance, mutational epitope inactivation, T cell receptor antagonism, incomplete down-regulation of viral replication and infection of immunologically privileged tissues. However, these pathways become apparent only in the setting of an ineffective immune response, which is, therefore, the fundamental underlying cause. Persistent infection is characterized by chronic liver cell injury, regeneration, inflammation, widespread DNA damage and insertional deregulation of cellular growth control genes, which, collectively, lead to cirrhosis of the liver and hepatocellular carcinoma.
La réponse immunitaire acquise est vraisemblablement responsable de l’éviction de virus et des désordres pathologiques observés pendant l’infection par le virus de l’hépatite B (VHB). Il est généralement admis que la réponse humorale par les anticorps contribue à l’élimination des particules virales de la circulation sanguine et à la limitation de la propagation du virus dans l’hôte ; tandis que les cellules infectées sont éliminées par la réponse immunitaire cellulaire. La réponse immunitaire contre le virus de l’hépatite B (VHB) par les cellules T est vigoureuse, polyclonale et de large spécificité, en phase aiguë de l’infection, chez les patients qui résolvent l’infection avec succès ; alors qu’elle est relativement médiocre et étroitement focalisés chez les patients infectés de façon chronique, ainsi ces observations suggèrent que la résolution de l’infection par le VHB dépend des cellules T. Les capacités antivirales et pathogéniques de la réponse par les lymphocytes T cytotoxiques (LTC) contre le VHB ont été mises en évidence par le développement d’une sévère inflammation nécrosée du foie, suite au transfert adoptif de LTC spécifiques pour les HBsAg, par des souris transgéniques pour VHB. De façon remarquable, les intermédiaires de réplication du VHB sont aussi purgés du foie par les LTC grâce à la sécrétion de cytokines inflammatoires, en conséquence de quoi la propagation du virus aux cellules qui ne sont pas infectées est limitée et le degré d’immunopathogenèse, nécessaire pour mettre fin à l’infection, est réduit. L’infection persistante par VHB est caractérisée par une faible réponse immunitaire adaptative en raison, vraisemblablement, d’un amorçage défaillant de la réponse par les cellules T CD4+ à un stade précoce de l’infection et du développement ultérieur d’une réponse par les cellules T CD8+, qui est inefficace sur un plan quantitatif et qualitatif. Comme autres facteurs qui pourraient contribuer à ce que l’infection perdure figurent la tolérance immunologique, l’inactivation par des mutations aux niveaux des épitopes, l’antagonisme des récepteurs des cellules T, une réduction incomplète de la réplication et de l’infection par le virus de tissus qui présentent des propriétés de privilège immun. Cependant, ces éventualités ne deviennent uniquement décelables lorsque la réponse immunitaire est défaillante ; par conséquent, celle-ci en constitue la cause primaire. L’infection, lorsqu’elle persiste, est caractérisée par les lésions chroniques des cellules du foie, le renouvellement, l’inflammation, les atteintes généralisées de l’ADN et le dérèglement par l’insertion des gènes qui contrôlent la croissance cellulaire ; ce qui, conjointement, conduit à la cirrhose du foie et le développement de tumeurs cancéreuses hépatiques.
Natural history of primary biliary cirrhosis
2008, Gastroenterologia y HepatologiaLa cirrosis biliar primaria es una enfermedad colestásica crónica que aparece generalmente en mujeres de mediana edad y tiene un curso lento y progresivo, con el desarrollo final de cirrosis. La enfermedad tiene tres formas de presentación: silente, asintomática y sintomática. La forma silente se caracteriza por la presencia de anticuerpos antimitocondriales como única anomalía. Las formas silentes y asintomáticas son menos agresivas y tienen un curso más lento. En el transcurso de la enfermedad algunos pacientes permanecen asintomáticos y no se han identificado características diferenciales entre éstos y los que desarrollan síntomas. La supervivencia es mejor en los pacientes asintomáticos que en los sintomáticos, y excelente en los pacientes que permanecen asintomáticos. Desde la introducción del tratamiento con ácido ursodesoxicólico se ha modificado el curso natural de la enfermedad, que es mucho más prolongado y con una supervivencia comparable a la población general en los casos con buena respuesta terapéutica.
Las variables clínicas y analíticas asociadas a un mal pronóstico son la edad, la bilirrubinemia, la albuminemia, el tiempo de protrombina, la ascitis, la encefalopatía hepática y el estadio histológico avanzado. Asimismo, la aparición de varices y el desarrollo de carcinoma hepatocelular comportan un peor pronóstico. La bilirrubinemia es, sin embargo, la variable con mayor peso para establecer el pronóstico. Hay distintos modelos pronóstico matemáticos que predicen sensiblemente la probabilidad de supervivencia y tienen utilidad para determinar la gravedad de la enfermedad en un paciente concreto.
Primary biliary cirrhosis is a chronic cholestatic disease that generally appears in middle-aged women. The clinical course is slow and progressive, finally leading to cirrhosis. This disease has three forms of presentation: silent, asymptomatic and symptomatic. The silent form is characterized by the presence of antimitochondrial antibodies as the only abnormality. The silent and asymptomatic forms are less aggressive and have a slower clinical course. During the course of the disease, some patients remain asymptomatic. No distinguishing features between asymptomatic patients and those who develop symptoms have been identified. Survival is better in asymptomatic than in symptomatic patients and is excellent in patients who remain asymptomatic. The introduction of treatment with ursodeoxycholic acid has greatly prolonged the natural course of the disease. In patients with good therapeutic response, survival is similar to that in the general population. The clinical and laboratory variables associated with poor prognosis are age, bilirubinemia, albuminemia, prothrombin time, ascites, hepatic encephalopathy and advanced histological stage. Likewise, the development of varices and of hepatocellular carcinoma carries a poor prognosis. Bilirubinemia is, however, the most important variable to establish prognosis. There are distinct mathematical prognostic models that sensitively predict the probability of survival and are useful to determine disease severity in specific patients.
Tumors of the Liver—Pathologic Aspects
2006, Surgery of the Liver, Biliary Tract and Pancreas: Volumes 1-2, Fourth Edition