RESUMO
UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
In some countries where the Model for End-Stage Liver Disease (MELD) score is used for graft allocation, selected patients with hepatocellular carcinoma (HCC) receive a fixed number of exception points at listing, and increasing priority on the list by accruing additional exception points at regular time intervals. This system originally aimed at balancing the risks of HCC patients of developing contraindications and of non-HCC patients of dying before transplantation, is not ideal because it appears to offer an advantage to HCC patients, regardless of tumor characteristics and response to loco-regional treatment. Scores modulated by HCC characteristics have been proposed. They are based on a more refined estimate of the risk of pretransplant drop-out or of the posttransplant transplant benefit expressed as the life-years gained for each graft. This review describes the newly proposed systems, and discusses their advantages and drawbacks. We believe that the current exception points allocation should be revised and that drop-out-equivalent or transplant benefit-equivalent models should be studied further. As with all policy changes, these should be done under close monitoring that allows subsequent revisions.
Assuntos
Carcinoma Hepatocelular/cirurgia , Alocação de Recursos para a Atenção à Saúde , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Estudos de Casos e Controles , Humanos , Pacientes Desistentes do TratamentoRESUMO
OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Adulto , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/epidemiologia , Biópsia por Agulha Fina , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/epidemiologia , Diagnóstico por Imagem , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Cirrose Hepática/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/complicações , Colangiocarcinoma/mortalidade , Feminino , Seguimentos , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor. METHODS: This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity. RESULTS: Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months. CONCLUSION: Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/tratamento farmacológico , Pirrolidinonas/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Feminino , Humanos , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Pirrolidinonas/efeitos adversos , Quinolinas/efeitos adversos , RetratamentoRESUMO
Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.
Assuntos
Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Europa (Continente)/epidemiologia , Hepatite B/complicações , Hepatite B/mortalidade , Hepatite C/complicações , Hepatite C/mortalidade , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Programas de Rastreamento/métodos , Vigilância da População/métodos , Vacinação/estatística & dados numéricosAssuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Gastroenterologia/normas , Saúde Global , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Sociedades Médicas/normas , Carcinoma Hepatocelular/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologiaRESUMO
Hepatocellular carcinoma is one of the major cancer killers. It affects patients with chronic liver disease who have established cirrhosis, and currently is the most frequent cause of death in these patients. The main risk factors for its development are hepatitis B and C virus infection, alcoholism and aflatoxin intake. If acquistion of risk factors is not prevented and cirrhosis is established, the sole option to improve survival is to detect the tumor at an early stage when effective therapy may be indicated. Early detection plans should be based on hepatic ultrasonography every 6 months, whereas determination of tumor markers is not efficient. Upon detection of a hepatic nodule, there is a need to establish unequivocal diagnosis, either through biopsy or through the application of non-invasive criteria based on the specific radiology appearance of the tumor: fast arterial uptake of contrast followed by venous washout. Effective treatment for liver cancer includes surgical resection, liver transplantation and percutaneous ablation. These options provide a high rate of complete responses and are assumed to improve survival that should exceed 50% at 5 years. If the tumor is diagnosed at an advanced stage, the sole option that improves survival is transarterial chemoembolization. Ongoing research should further advance the time at diagnosis and identify new and effective options targeting molecular pathways governing tumor progression.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgiaRESUMO
The objective of this study was to assess the efficacy of contrast-enhanced ultrasonography (CEUS) with SonoVue to evaluate the response to percutaneous treatment (ethanol injection/radiofrequency) of hepatocellular carcinoma in comparison with spiral computed tomography (CT) immediately and 1 month after treatment. Forty-one consecutive cirrhotic patients with early stage tumor (not suitable for resection) were included. Spiral CT and CEUS were performed in all patients before treatment, in the following 24 h, and 1 month later. The results of each examination were compared with the 1-month spiral CT, considered the gold standard technique. The 24-h CEUS and the 24-h spiral CT sensitivity to detect residual disease were 27% and 20%, respectively. The 24-h CEUS and the 24-h spiral CT positive predictive value of persistent vascularization detection were 75% and 66%, respectively. The 1-month CEUS detected partial responses in ten out of 11 cases (91% sensitivity, 97% specificity, 95% accuracy). Spiral CT and CEUS performed in the 24 h following treatment are slightly useful to evaluate therapeutic efficacy. The 1-month CEUS has a high diagnostic accuracy compared with spiral-CT in the usual assessment of percutaneous treatment response.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Ablação por Cateter , Aumento da Imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Microbolhas , Ultrassonografia de Intervenção/métodos , Administração Cutânea , Idoso , Carcinoma Hepatocelular/cirurgia , Depressores do Sistema Nervoso Central/uso terapêutico , Etanol/uso terapêutico , Reações Falso-Positivas , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosfolipídeos/administração & dosagem , Fosfolipídeos/metabolismo , Estudos Prospectivos , Sensibilidade e Especificidade , Hexafluoreto de Enxofre/administração & dosagem , Hexafluoreto de Enxofre/metabolismo , Fatores de Tempo , Tomografia Computadorizada Espiral , Resultado do Tratamento , Carga TumoralRESUMO
Hepatocellular carcinoma is a frequent neoplasm that usually develops in patients with liver cirrhosis. Because it is the main cause of death in these patients, they should be included in a surveillance program in order to identify these tumors at an early stage and be able to indicate curative treatment (liver transplantation, surgical resection or percutaneous ablation therapy) and to reduce mortality. Surveillance should include determination of alpha-fetoprotein and abdominal ultrasound every 6 months. This strategy should only be applied to patients suitable to receive curative treatment if diagnosed of hepatocellular carcinoma. Using this approach, 40-80% of tumors identified are solitary at diagnosis, although only half of these patients can benefit from curative treatment.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/etiologia , Diagnóstico Precoce , Humanos , Neoplasias Hepáticas/etiologia , Vigilância da População , Fatores de RiscoRESUMO
Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.
Assuntos
Vírus da Hepatite B/genética , Neoplasias Hepáticas/virologia , Papillomaviridae/genética , Telomerase/genética , Neoplasias do Colo do Útero/virologia , Integração Viral , Sequência de Bases , Proteínas de Ligação a DNA , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/etiologia , Dados de Sequência Molecular , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/etiologiaRESUMO
The knowledge of the natural history of patients with hepatocellular carcinoma is important to estimate the prognosis at diagnosis and indicate the best therapy. Prognosis is related to tumour stage at diagnosis, degree of liver function impairment induced either by the tumour itself or by the underlying cirrhosis, general physical condition of the patients, and potential impact of therapy. Prognostic estimation should take into account all four aspects. Treatment is very relevant to be considered in patients with early stage tumours since surgical resection, transplantation or percutaneous ablation provide a high rate of complete responses and thus, improve survival. This might be as high as 50-75% at 5 years. Patients diagnosed at an intermediate/advanced stage will receive palliative treatment and prospective studies have recently redefined the outcome predictors of this stratum. Asymptomatic patients in whom the tumour has not invaded vessels or disseminated may reach a 50% survival at 3 years, while those with adverse predictors do not reach this time point. These data have to be taken into account not only in the conventional clinical practice, but also in the design and evaluation of prospective investigations that should be properly powered to reach an informative sample size. To achieve both aims, within the Barcelona Clinic Liver Cancer Group we have developed a staging system that combines prognosis prediction with decision making, thus becoming a useful tool both for practice and research.
Assuntos
Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Estadiamento de Neoplasias/métodos , PrognósticoRESUMO
BACKGROUND: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. AIMS: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. METHOD: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment-resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. RESULTS: Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8-6.1 months with an acceptable cost ($40,000/ year of life gained) for waiting lists > or = 1 year whereas it was not cost effective ($74,000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2-6.7 months with a marginal cost of approximately $20,000/year of life gained in all cases, remaining cost effective for all waiting times. CONCLUSIONS: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/economia , Listas de Espera , Carcinoma Hepatocelular/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Etanol/administração & dosagem , Humanos , Expectativa de Vida , Neoplasias Hepáticas/economia , Cadeias de Markov , Modelos Econômicos , Pacientes Desistentes do Tratamento , Sensibilidade e EspecificidadeRESUMO
Only a minority of patients with hepatocellular carcinoma (HCC) may benefit from curative treatments, whereas there is no standard therapy for the remaining patients. The objective of this multicentre, open label phase II study was to estimate the objective tumour response rate of a 28-day regimen of oral eniluracil/5-fluorouracil (5-FU) in patients with chemotherapy-naïve, or anthracycline-refractory, inoperable HCC. 45 patients received courses of twice daily oral 5-FU (1.0 mg/m(2)) and eniluracil (10 mg/m(2)) for the first 28 days of each 5-week course. Patients were assessed at regular intervals to determine the tumour response and to evaluate toxicity. Patients were followed-up for a minimum of 6 months. No patient showed a partial or complete tumour response, and 18 patients (40%) had a best response of stable disease (95% confidence interval (CI) 25%, 55%). The median duration of progression-free survival (PFS) was 13.7 weeks (95% CI 10.0-20.0 weeks), and the median duration of overall survival (OS) was 50.3 weeks (range 1.1-64.1+ weeks). The combination of eniluracil/5-FU was well tolerated and had an acceptable safety profile. Only 7 patients (16%) reported at least one adverse event (AE) of grade 3 or 4 intensity considered reasonably attributable to the study medication. In conclusion, oral eniluracil/5-FU had minimal, if any, activity in patients with inoperable HCC, but the safety profile was acceptable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Uracila/administração & dosagem , Uracila/efeitos adversos , Uracila/análogos & derivadosRESUMO
Interferon therapy may decrease the risk of hepatocellular carcinoma in patients with hepatitis C virus (HCV)-related liver cirrhosis. Interaction of the cellular protein kinase PKR with the PKR-binding domain (PKR-bd) of HCV-NS5A protein may affect cellular growth control and viral resistance to interferon therapy. Mutations within the PKR-bd, which comprises the interferon sensitivity determining region (ISDR), have been associated with interferon sensitivity. To determine whether or not there is an association between HCV heterogeneity and the presence of hepatocellular carcinoma, HCV-1b genomic regions were amplified and directly sequenced from serum samples obtained from 82 patients with liver cirrhosis, 53 with, and 29 without hepatocellular carcinoma. None of them had received antiviral therapy. When compared with the deduced consensus sequence, the median number of amino acid changes in the PKR-bd was higher among samples from patients with (4.22) than from those without hepatocellular carcinoma (1.62; P <.001), and isolates with 3 or more amino acid changes were significantly more common among the former (60%) than among the later (6%, P <.001). No such differences were observed in other viral regions, including Core, E2-HVR-1, E2-PePHD, NS3, and the 5' and 3' PKR-bd flanking regions. In addition, amino acid variation in viral regions other than HVR-1 did not accumulate over time in the analyzed sequential serum samples obtained from patients with or without hepatocellular carcinoma. Therefore, a mutated HCV-PKR-bd phenotype is very common in cirrhotic patients with hepatocellular carcinoma.