Impact of etiology of cirrhosis on the survival of patients diagnosed with hepatocellular carcinoma during surveillance (original) (raw)
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BMC Cancer, 2007
Aims: Hepatocellular carcinoma (HCC) represents O90% of primary liver neoplasms and develops mainly in patients with liver cirrhosis. Risk factor identification for the development of HCC in patients with cirrhosis possesses great clinical relevance due to its high incidence and poor prognosis when detected at advanced stages. The aim of this study was to identify HCC development-associated risk factors in a cohort of patients with hepatitis virus-related chronic liver disease and cirrhosis. Materials and methods: Patients with a diagnosis of hepatitis virus-related cirrhosis between January 1980 and January 2000 were included. Patients were followed with an abdominal ultrasound and the determination of alpha-fetoprotein levels, a physical examination, and routine biochemical tests every 3e6 months. The end point of the study was defined as the development of HCC. Liver histology was evaluated according to the French METAVIR Cooperative Study Group (METAVIR) score. Results: Two hundred and eighty-two patients met the inclusion criteria; most of these (86%) had a serologic diagnosis of hepatitis C virus, and only 14% had hepatitis B virus at the time of the diagnosis of cirrhosis, whereas 56 and 37% were classified as Child A and B, respectively, and only 7% as Child C. Histological activity was mild in 59% of patients, and moderate and severe in 41%. The mean annual incidence was 1.87%, and 22 and 35% of patients developed HCC at 10 and 15 years of follow-up, respectively. The diagnosis of HCC was made by histopathology in 37% and by tumoural lesionassociated alpha-fetoprotein elevation confirmed by imaging studies in 63%. In multivariate analysis, we found three variables associated with HCC: moderate to severe histological activity; a platelet count !105 3 10 3 /mm 3 , and alphafetoprotein O5 ng/ml. The patients were divided into two groups according to regression coefficient: low and high risk; patients assigned to the low-risk group showed 5-, 10-and 15-year HCC incidences of 3.4, 6.4 and 6.4%, respectively, in contrast to patients from the high-risk group, who showed incidences of 17.8, 33.5 and 56.8%, respectively. Conclusions: We found three HCC-associated variables: histological activity, platelet count and alpha-fetoprotein levels. Patients considered as high risk for developing HCC must be considered candidates for closer follow-up. Rodríguez-Díaz,
Clinical Gastroenterology and Hepatology, 2018
BACKGROUND & AIMS: Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. METHODS: In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64 years; range, 28-87 years; 60% male, 49% infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87% Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3-6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. RESULTS: During a median 25 months of follow up (range, 3-39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6% (95% CI, 4%-9%). Of patients with de novo HCC, 75% had a single tumor and 82% of these were Barcelona liver cancer stage 0-A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0-9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95% CI, 1.44-26.47; P [ .01), diabetes (HR, 2.52; 95% CI, 1.08-5.87; P [ .03), LSM (HR, 1.03; 95% CI, 1.01-1.06; P [ .01), and FIB-4 score (HR, 1.08; 95% CI, 1.01-1.14; P [ .01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3year cumulative probability for recurrence was 43% (95% CI, 20%-61%). In the 20 patients with HCC recurrence, 11 had a single tumor and 90% were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95% CI, 1.55-10.93; P [ .004).
Liver International, 2006
Abstract: Background: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies.Methods: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39±2 months.Results: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p=0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p=0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival.Conclusion: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.
Digestive and Liver Disease, 2011
Background: The aetiological factors of hepatocellular carcinoma may vary over time. Aims: The study assessed the potential impact of the aetiological factors on the effectiveness of surveillance in real-world patients. Methods: Multicentre, cross-sectional study enrolling consecutive hepatocellular carcinoma cases during a six month period. Results: 1733 cases (1311 prevalent and 422 incident) were recruited (mean age 68.6 years; 46.1% cases over 70 years; 73.9% males; 95.3% with cirrhosis); 63.0% were hepatitis C virus positive and 23.7% were virus negative. Amongst incident HCCs, 34.5% were single ≤3 cm and 54.4% met the Milan criteria; 61.6% were diagnosed during surveillance; virus negative patients showed the lowest rate of surveillance (51.0%). Surveillance was an independent predictor of detecting single HCCs ≤2 cm (O.R. = 5.4; 95% C.I. = 2.4-12.4) or HCCs meeting the Milan criteria (O.R. = 3.1; 95% C.I. = 1.9-5.2). Compared with an earlier Italian survey, there was a higher proportion of elderly subjects (P < 0.01), Child-Pugh class A cases (P < 0.01), of virus-negative patients (P < 0.01) and with single tumours ≤3 cm (P < 0.01) and a lower prevalence of hepatitis C virus positive individuals (P < 0.01). Conclusion: HCC is characterised by a growing prevalence of elderly patients and cases unrelated to hepatitis virus infections. The application of surveillance must be implemented, particularly amongst non-viral patients.
Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis
Journal of Cancer Research and Clinical Oncology, 1998
The incidence, risk factors, and clinical features of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC) have been a long-standing subject of interest. We took advantage of a large cohort of 1865 well-defined Chinese patients with PBC for whom follow-up was conducted for up to 20 years to study the incidence of HCC. Our goal was to address the incidence and prevalence of HCC in PBC and the risk factors, including hepatitis B virus (HBV) infection, and finally to compare the tumor characteristics of PBCrelated HCC, including size, location, mortality, and longterm outcomes, to that of HBV-related HCC. In this cohort, HCC occurred in 70 of 1865 PBC patients with a prevalence of 3.75 % and an incidence of 0.66 cases per 100 patientyears. The 5-and 10-year cumulative incidences were 2.6 % (95 % confidence interval (CI) 1.8-3.4) and 8.9 % (95 % CI 5.5-12.3), respectively. Age >54 years (odds ratio [OR]=5.5, 95 % CI 3.0-10.1, p=0.001), male sex (OR=2.2, 95 % CI 1.2-4.0, p=0.001), coexistence of diabetes mellitus (DM) (OR=3.1, 95 % CI 1.6-6.2, p=0.002), and previous HBV infection (OR=6.6, 95 % CI 3.7-11.9, p=0.001) were independently associated with the development of HCC. The tumor size, number, location, and 5-year survival were not significantly different in PBC-related HCC compared to HBVrelated HCC. Alpha-fetoprotein was elevated in only 20 % of the cases with PBC-related HCC. Although HCC was uncommon, occurring in fewer than 5 % of patients, the risk is significantly increased by age, sex, DM, and past HBV infection.
Hepatology, 1999
To see whether or not there is an association between the cause of cirrhosis and the number of hepatocellular carcinoma (HCC) nodules, we analyzed 178 consecutive patients in whom HCC was detected during a prospective screening by abdominal ultrasound (US). The relevant information was obtained from the database of the screening programs operating at four hospitals in the Milan area. One hundred twenty-nine (72%) patients had a single tumor nodule detected by US and 49 (28%) patients had multinodular disease. Ninety-eight (55%) patients had normal serum values of ␣-fetoprotein (AFP). Tumor staging with biphasic computed tomography (CT) scan or hepatic arteriography with lipiodol revealed that 101 (57%) patients had single tumor nodules and 77 (43%) patients had more than one HCC nodule. After staging, multinodular HCC was more common in patients with multiple risk factors than in the hepatitis C virus (HCV) carriers (56% vs. 38%, P ؍ .05). Interestingly, single tumors were as common in the 126 patients undergoing 6-month interval screening as in the 52 patients who were studied at yearly intervals. The former patients, however, had more small tumors than the latter ones (91% vs. 74%, P ϭ .04). The 22 patients who were alcohol abusers had normal levels of serum AFP more often than the hepatitis B virus (HBV) or HCV carriers or those with multiple risk factors (86% vs. 57%, P F .04; vs. 47%, P F .002; vs. 52%, P F .006, respectively). We concluded that multinodular HCC was underdetected by real time US; it prevailed among patients with multiple risk factors. In these patients, screening with US exams every 6 months may be inadequate for early detection of liver cancer. (HEPATOLOGY 1999;29:1704-1707
2023
Objectives Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis, but can also develop in noncirrhotic livers. In the present study we explored associated risk factors for HCC without cirrhosis and compared patient and tumor characteristics and outcomes in HCC patients with and without underlying cirrhosis. Methods Patients with HCC diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated. Patients were categorized according to the presence of cirrhosis on the basis of histology or combined radiological and laboratory features. Results In total, 19% of the 1221 HCC patients had no underlying cirrhosis. Noncirrhotic HCC patients were more likely to be female and to have nonalcoholic fatty liver disease or no risk factors for underlying liver disease, and less likely to have hepatitis C virus or alcohol-related liver disease than did cirrhotic HCC patients. HCCs in noncirrhotic livers were more often unifocal (67 vs. 48%), but tumor size was significantly larger (8 vs. 4 cm). Despite the larger tumors, more patients underwent resection (50 vs. 10%) and overall survival was significantly better than in cirrhotics. In multivariate analyses, absence of cirrhosis [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.38-0.63] and presence of hepatitis B (HR 0.68, 95% CI 0.51-0.91) were independent predictors for lower mortality, whereas hepatitis C virus was associated with higher mortality (HR 1.32, 95% CI 1.01-1.65). Conclusion HCC without cirrhosis was strongly associated with female sex and presence of nonalcoholic fatty liver disease or no risk factors for underlying liver disease. In absence of cirrhosis, resections were more often performed, with better survival despite larger tumor size.