Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance (original) (raw)
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Hepatitis C and hepatocellular carcinoma
Current Treatment Options in Oncology, 2001
Chronic hepatitis C virus infection is a well-recognized risk factor for occurrence of hepatocellular carcinoma (HCC). In Europe, Oceania and America, chronic hepatitis C and alcoholic cirrhosis are the main risk factors for HCC. In Latin America, a few retrospective and one prospective study have also shown the predominant role played by hepatitis C in this setting. Furthermore, the incidence of HCC has been increasing in industrialized countries in the last decades; partially as a consequence of the increase in HCV-related cirrhosis (as the long-term sequel of the peak of infections occurring 2-4 decades ago). The main risk factor for HCC development in patients with hepatitis C is the presence of cirrhosis. Among patients with hepatitis C and cirrhosis, the annual incidence rate of HCC ranges between 1-8%, being higher in Japan (4-8%) intermediate in Italy (2-4%) and lower in USA (1.4%). Some studies have also found that HCC may be the first complication to develop and the more frequent cause of death in the compensated HCV-associated cirrhosis. Other risk factors for HCC occurrence are older age at infection, male gender, decreased platelet count, esophageal varices, presence of porphyria cutanea tarda, liver steatosis or diabetes, infection with genotype 1b, coinfection with hepatitis B virus or with HIV and chronic alcoholism. Many studies and also meta-analysis have reported that antiviral therapy based on interferon may reduce the incidence of HCC in chronic hepatitis C, especially in patients with sustained virologic response. Patients with HCV-related cirrhosis should undergo surveillance for HCC.
Hepatology, 2002
This systematic review addresses the following questions: (1) What is the efficacy of using screening tests for hepatocellular carcinoma (HCC) in improving outcomes in chronic hepatitis C, and (2) what are the sensitivity and specificity of screening tests for HCC in chronic hepatitis C? The search strategy involved searching Medline and other electronic databases between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Articles were eligible for review if they reported original human data from studies of screening tests that used virological, histological, pathologic, or clinical outcome measures. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis C or B or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45% to loo%, with a specificity of 70% to 95%, for a threshold of between 10 and 19 ng/mL. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. In conclusion, screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves c h i d outcomes. (HEPATOLOGY 2002;36:S84S92.) H epatocellular carcinoma (HCC) is one of the most common non-dermatologic cancers in the world. Incidence rates vary regionally with rates reported in Asia as high as 80 per 100,OOO.l The incidence Abbreviations: HCC, hepatocellular carcinoma: HCK hepatitis C virus: HBK
Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study
European Journal of Gastroenterology & Hepatology, 1996
approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to establish tients can usually be achieved by screening with noninvasive whether infection with specific hepatitis C virus (HCV) techniques, such as ultrasound (US) scan and serum a-fetogenotypes was associated with an increased risk of protein (AFP) concentration. 5,6 development of hepatocellular carcinoma (HCC) in cir-Over the years, several lines of experimental evidence indirhosis. A cohort of 163 consecutive hepatitis C virus anticated that male sex, age, and alcohol consumption 4,7,8 were body (anti-HCV)-positive cirrhotic patients was proclosely associated with the development of HCC in cirrhotic spectively evaluated for the development of HCC at patients. The identification of additional variables associated 6-month intervals by ultrasound (US) scan and awith an increased risk of developing HCC would be particufetoprotein (AFP) concentration. HCV genotypes were larly important to optimize preventive medical programs in determined according to Okamoto. Risk factors associthis setting. Recent studies suggested a possible role for HCV ated with cancer development were analyzed by univarigenotype in chronic liver disease outcome and, specifically, ate and multivariate statistics. At enrollment, 101 pa-HCV type 1 was more frequently found in advanced liver tients (62%) were infected with type 1b, 48 (29.5%) were disease, such as cirrhosis and HCC, 9-11 and was associated infected with type 2a/c, 2 (1.2%) were infected with type with a more rapid deterioration of liver histology in chronic 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a hepatitis. 12 We have studied the distribution of HCV genomixed-type infection, and, in 8 patients (4.9%), genotype types in a cohort of patients with cirrhosis prospectively folcould not be assigned. After a 5-to 7-year follow-up (melowed for early detection of HCC, and we performed multivardian, 68 months), HCC developed in 22 of the patients, iate analysis to evaluate the independent risk for tumor 19 infected with type 1b and 3 with type 2a/c (P õ .005). development associated with specific HCV types and with Moreover, HCC developed more frequently in males (P other variables, including interferon treatment, which has õ .01), patients with excessive alcohol intake (P õ .01), been recently reported to reduce the cancer risk in HCVthose over 60 years of age (P õ .02), and in patients who induced cirrhosis. 13 did not receive interferon treatment (P õ .02). Multivariate analysis showed that type 1b was the most important PATIENTS AND METHODS risk factor associated with tumor development (odds ra-Patients. Between January 1989 and December 1990, all cirrhotic tio 6.14, 1.77-21.37 95% confidence interval). Other indepatients (nÅ 501) attending the outpatient clinic were enrolled in a pendent risk factors were older age and male sex. Cirprospective study aimed at early recognition of HCC. Of these, 109 rhotic patients infected with HCV type 1b carry a were patients already included in a follow-up program, and 392 were significantly higher risk of developing HCC than panew referrals. The diagnosis of cirrhosis was confirmed histologically tients infected by other HCV types. The latter may reor based on clinical signs of portal hypertension as esophageal or quire a less intensive clinical surveillance for the early gastric varices, ascites, and splenomegaly. At enrollment, complete detection of neoplasia. (HEPATOLOGY 1997;25:754-758.) medical history and physical examination were obtained for each patient, and serological and biochemical screenings were performed, which included standard liver function tests, AFP, and hepatitis B Hepatitis C virus (HCV) is a major etiological agent associand delta virus markers. The Child-Turcotte score, modified by Pugh, ated with the development of cirrhosis. 1 HCV infection alone was also calculated. Aliquots of sera collected at entry were stored accounts for over 25% of all cases of cirrhosis in Italy, 2 a at 030ЊC for further serological and molecular analysis. When hepacondition that is associated with an increased risk of hepatotitis C virus antibody (anti-HCV) serology became available, sera cellular carcinoma (HCC), with a yearly incidence rate of from 472 of 501 patients were tested by second-generation enzyme immunoassay (Ortho Diagnostic Systems, Raritan, NJ), and 240 subjects (51%) were found to be anti-HCV-positive. Seventy-seven anti-HCV-positive patients were further excluded from the study Abbreviations: HCV, hepatitis C virus; HCC, hepatocellular carcinoma; US, ultrasound; according to the following criteria: 1) evidence for, or suspicion of, AFP, a-fetoprotein; anti-HCV, hepatitis C virus antibodies.
Journal of Medical Virology, 2001
The associations between types of HCV and tumor characteristics and recurrence and survival after treatment of small HCC were investigated. Viral genotype-speci®c antibodies were measured in sera obtained at the time of diagnosis of HCC, in 92 patients with HCC 2 cm in diameter who were treated between 1990 and 1998. The degrees of tumor differentiation and angiographically-evaluated hypervascularity were compared between patients infected with HCV type 1 and those with type 2. Survival, time to recurrence, and patterns of recurrence after initial treatment also were compared. On pathologic evaluation, 6 of 21 HCC (28.6%) in patients with HCV type 2 were well-differentiated, whereas 28 of 48 HCC (58.3%) in patients with HCV type 1 were well-differentiated (P 0.0229). HCC in patients with HCV type 2 showed hypervascularity more frequently than HCC in patients with HCV type 1, with tumor staining evident by digital subtraction arteriography in 17 of 22 patients with HCV type 2 (77.3%) vs. 20 of 50 in patients with HCV type 1 (40.0%, P 0.0036). Survival and overall recurrence rates were similar in patients infected with HCV type 1 and with HCV type 2 (P 0.5537). In the analyses of patterns of recurrence, recurrences in patients infected with HCV type 2 were relatively more likely to be intrahepatic metastases (P 0.0342), that was closely related to the differentiation of HCC. Multicentric occurrence of HCC was a more frequent type of recurrence in patients with HCV type 1 (P 0.1619), and infection of HCV type 1 was an independent factor for multicentric occurrence in multivariate analysis (P 0.0021). In HCC 2 cm in diameter, HCV type 2 is associated with more progression of HCC than HCV type 1, whereas patients with HCV type 1 may be at higher risk for multicentric HCC occurrence after the treatment of HCC.
Hepatoma Research
Aim: Hepatitis C virus (HCV) cirrhosis is an important cause of hepatocellular carcinoma (HCC). This study aimed to identify factors of HCC presence among HCV cirrhotic patients with and without small diameter HCC (≤ 3 cm). Methods: A case control transversal study between 1998 and 2003 including 93 patients: 31 with small diameter HCC and 62 without HCC. Groups were matched by age and gender. Multiple logistic regression analysis using Akaike Information Criteria to estimate the probability of HCC was performed. A model score was generated and bootstrap analysis was performed for internal validation. Results: Three significant laboratorial variables for HCC presence were found: alanine aminotransferase > 37 U/L [odds ratio (OR): 7.43 (1.61-34.19), P = 0.01], alpha-fetoprotein > 20 ng/mL [OR: 16.2 (4.17-63.01), P < 0.001] and platelet count < 100,000/mm 3 [OR: 3.62 (1.43-9.14), P = 0.007]. A model score with an area under curve of 0.79 (95% CI: 0.7-0.89) was built based on these variables. The negative predictive value of those classified as at low risk of HCC was 99.1%. Conclusion: An easy and practical model score was generated. It may be an auxiliary tool for identification of HCV patients with low probability of small diameter HCC at initial evaluation composed of three serum examinations used in routine outpatient clinical practice.
Journal of Clinical Gastroenterology, 2002
Background: The aim of this study was to determine whether hepatitis C virus (HCV) is an underlying cause of the increase in the incidence of hepatocellular carcinoma (HCC) in the United States. Study: The medical records of all patients who had received a pathologic diagnosis of HCC at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A., during 1993 through 1998 were reviewed. Only patients residing in the United States were analyzed. All patients were tested for HCV and hepatitis B virus serologic markers. Results: The number of patients with HCC referred to M.D. Anderson Cancer Center increased from 143 in 1993 through 1995 to 216 in 1996 through 1998. Twenty-six patients (18%) and 66 patients (31%) with anti-HCV antibodies were diagnosed with HCC from 1993 to 1995 and from 1996 to 1998, respectively, thus constituting a significant increase (p ס 0.01). Although the age distribution of these patients did not differ significantly between 1993 to 1995 and 1996 to 1998, the increase in HCV-associated HCC was greatest among patients 40 to 49 years old. Hepatitis B surface antigens (HBsAg) or anti-hepatitis B core antigens were found in 37 patients (26%) with HCC during 1993 to 1995 and in 37 patients (17%) with HCC during 1996 to 1998 (p ס 0.06). Moreover, a significant decrease in the prevalence of HBsAg from 1996 to 1998 (21 patients; 10%) compared with 1993 to 1995 (25 patients; 18%) was observed (p ס 0.03). Conclusion: Hepatitis C infection is the major viral factor contributing to the increase in HCC incidence observed in this large-scale, single-center United States-based experience.
Prevalence of Hepatocellular Carcinoma in Hepatitis C Patients
2018
Background: The major risk for HCC is HCV and HBV among developed and under developed countries. The utmost cause of liver transplant among US population with HCC was also considered to HCV. The fibrosis stage plays an important role among chronic HCV patients and associated to HCC risk. Although the annual incidence of HCC is high in cirrhotic cases and lessly developed in less fibrosis livers. Methods: This was an observation cohort study where a total of 100 HCV patents were screened for HCC and risk factors associated. The exclusion criteria include all the patients with Hepatitis B and renal failure, whereas the patients with chronic Hepatitis C (HCV) of both genders were included.. Results: The study cohort constitute of total of 100 patients, where all of them were HCV positive. The mean age of the patient was 42+8.9. 62(62%) of the patients were males and 38(38%) were females. Most of the HCC patients were with elevated AFP. AFP has sensitivity, specificity positive predicti...
Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death
Gut, 2000
Background-In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated. Design-From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 1998). The analysis used a three state disability model generalising the Cox model. Results-Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR 2.36; p= 0.008), decreased platelet count (HR 0.99; p=0.03), and bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001).