Cirrhosis Carcinoma Research Articles

Predictive factors of survival and intrahepatic recurrence of hepatocellular carcinoma in cirrhosis after percutaneous ethanol injection: analysis of 71 patients

Background/Aims: This study was undertaken to determine the factors predicting survival and intrahepatic recurrence in hepatocellular carcinoma patients treated with percutaneous ethanol injection. Methods: Seventy-one patients with cirrhosis and hepatocellular carcinoma underwent percutaneous ethanol injection (54 males/17 females; median age 66 years; Child a 54/B 17). Fifty-two patients had a single nodule ≤5 cm and 19 had multiple nodules, up to three, each one ≤4 cm. Follow-up ranged from 2–63 months (median 26). Results: Overall survival rates were 89%, 54% and 24% and new lesions recurrence rates 32%, 73% and 81% at 1, 3 and 5 years, respectively. At univariate analysis, monofocal tumor ( p<0.05), absence of ascites ( p<0.05), complete tumor necrosis at CT-scan or MIR ( p<0.01), post-treatment α-fetoprotein ≤10 ng/ml ( p<0.05) and Child A class in patients with a single nodule ( p<0.05) were associated with higher survival. Presence of tumor capsule at imaging ( p<0.05), complete tumor necrosis at CT-scan or MRI ( p<0.01) and post-treatment α-fetoprotein ≤10 ng/ml ( p<0.01) were associated with lower recurrence rates. At multivariate analysis, basal α-fetoprotein ( p=0.040) and tumor number ( p=0.032) significantly affected survival; stepwise analysis revealed basal α-fetoprotein, tumor number and serum albumin ( p=0.0012) as the best combination predicting survival. No variable reliably predicted recurrence by multivariate analysis. Conclusions: In patients with cirrhosis and hepatocellular carcinoma, treated with percutaneous ethanol injection, survival depends on: the severity of the underlying liver disease, uni/multifocality of the tumor and basal α-fetoprotein. Presence of a tumor capsule is associated with lower recurrence rates. At post-treatment evaluation, both survival and recurrence rates are positively affected by complete tumor necrosis and α-fetoprotein ≤10 ng/ml.

Hepatitis C virus infection in the development of hepatocellular carcinoma in cirrhosis

Background/Aims: The role of hepatitis C virus replication and different genotypes in the progression of cirrhosis to hepatocellular carcinoma is examined on the basis of a prospective follow-up of 1438 patients with histologically proven cirrhosis. Methods: The presence of HCV RNA, anti-HCV and characterisation of virus genotypes were determined in 72 cases who developed hepatocellular carcinoma after a median follow-up of 5.3 years range 1 to 16) and compared to 72 controls who had cirrhosis only, after a median follow-up of 4.8 hears (range 1 to 16). Patients in the hepatocellular carcinoma group and controls were matched, one to me, for age, sex, nationality, HBsAg seropositivity, duration of follow-up and aetiology of cirrhosis. Results: HCV RNA was detected in 31 of 72 (44%) patients who developed hepatocellular carcinoma, significantly more frequently than in 17 of 72 (23%) controls with cirrhosis (odds ratio 2.4, 95% confidence interval 1.2 to 5.0; p=0.013). When cirrhosis of different aetiologies was analysed, hepatitis C virus replication was more frequently detected in patients developing hepatocellular carcinoma in association with cryptogenic cirrhosis ( p=0.007), alcoholic cirrhosis ( p=0.043) and hepatitis B virus seronegative cirrhosis ( p=0.05). Hepatitis C virus genotypes 1b and 4 were the most prevalent; they were found in 53% and 25%, respectively, of the patients studied, but were equally distributed between cirrhosis progressing to hepatocellular carcinoma and controls. Conclusions: Persistent hepatitis C virus replication is closely associated with hepatocellular carcinoma development in cirrhosis, and there is no preferential role of individual hepatitis C virus genotypes.

Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience.

The objective of our work was to evaluate the long-term results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. A total of 184 cirrhotic patients with HCC underwent PEI as the only anticancer treatment over an 8-year period. Patients were followed after therapy by means of clinical examinations, laboratory tests, and US and CT studies performed at regular time intervals. Survival rates were determined according to the Kaplan-Meier method. The overall survival was 67% at 3 years, 41% at 5 years, and 19% at 7 years. The 3-, 5-, and 7-year survival rates of patients with single HCC < or = 3 cm (78, 54, and 28%, respectively) were significantly higher (p < 0.01) than those of patients with single HCC of 3.1-5 cm (61, 32, and 16, respectively) or multiple HCCs (51, 21, and 0%, respectively). Survival of Child-Pugh A patients (79% at 3 years, 53% at 5 years, and 32% at 7 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (50% at 3 years, 28% at 5 years, and 8% at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and single HCC < or = 3 cm had a 7-year survival of 42%. Long-term survival of cirrhotic patients with HCC treated with PEI is comparable to that reported in published series of matched patients submitted to surgical resection.

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study.

A prospective study was performed to establish whether infection with specific hepatitis C virus (HCV) genotypes was associated with an increased risk of development of hepatocellular carcinoma (HCC) in cirrhosis. A cohort of 163 consecutive hepatitis C virus antibody (anti-HCV)-positive cirrhotic patients was prospectively evaluated for the development of HCC at 6-month intervals by ultrasound (US) scan and alpha-fetoprotein (AFP) concentration. HCV genotypes were determined according to Okamoto. Risk factors associated with cancer development were analyzed by univariate and multivariate statistics. At enrollment, 101 patients (62%) were infected with type 1b, 48 (29.5%) were infected with type 2a/c, 2 (1.2%) were infected with type 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a mixed-type infection, and, in 8 patients (4.9%), genotype could not be assigned. After a 5- to 7-year follow-up (median, 68 months), HCC developed in 22 of the patients, 19 infected with type 1b and 3 with type 2a/c (P < .005). Moreover, HCC developed more frequently in males (P < .01), patients with excessive alcohol intake (P < .01), those over 60 years of age (P < .02), and in patients who did not receive interferon treatment (P < .02). Multivariate analysis showed that type 1b was the most important risk factor associated with tumor development (odds ratio 6.14, 1.77-21.37 95% confidence interval). Other independent risk factors were older age and male sex. Cirrhotic patients infected with HCV type 1b carry a significantly higher risk of developing HCC than patients infected by other HCV types. The latter may require a less intensive clinical surveillance for the early detection of neoplasia.

Unresectable hepatocellular carcinoma in cirrhosis: survival, prognostic factors, and unexpected side effects after transcatheter arterial chemoembolization.

To evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma, the prognostic factors, and the side effects, 72 patients undergoing 170 chemoembolizations with lipiodol-mediated injection of adriamycin were investigated. The 1-, 2-, and 3-year survivals are 83, 61, and 56%, respectively. Significant prognostic factors for survival (by Mantael-Haenszel) are Child-Pugh and Okuda status (p = 0.00001 and p = 0.01 respectively), number of TACE courses (p = 0.002) and of courses completed with embolization (p = 0.05), stabilization or reduction of alpha-fetoprotein (p = 0.003), and concurrent tamoxifen treatment (p = 0.04). Side effects included fever, pain, increased serum amylase and transaminase levels, and one liver abscess with death of liver failure. In addition, mild hyperglycemia was observed in 19% of patients and severe in 8% (with one hyperosmolar diabetic coma), in the absence of pancreatic damage. In conclusion, transcatheter arterial chemoembolization is useful in patients with unresectable hepatocellular carcinoma. Prognostic factors are Child-Pugh and Okuda status, number of TACE courses and of embolizations, changes of alpha-fetoprotein levels, and association with tamoxifen treatment. The development of mild to severe changes of glucose metabolism suggests that glucose tolerance should be evaluated before and glycemia strictly monitored after each TACE course.

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study

Silini, E; Bottelli, R; Asti, M; Bruno, S; Candusso, M E; Brambilla, S; Bono, F; Iamoni, G; Tinelli, C; Mondelli, M U; Ideo, G

Feasibility of intra-arterial chemotherapy followed by chemoembolization, every 28 days, in unresectable hepatocellular carcinoma

Encouraging response rates and survival have been reported with intra-arterial (i.a.) chemotherapy and chemoembolization, but limited data are available on the association of the two treatment modalities. We therefore started a feasibility study of i.a. chemotherapy plus chemoembolization, performed every 28 days for 3 cycles, according to the following schedule: L-leucovorin (100 mg/m(2) i.v.), fluorouracil (800 mg/m(2) i.a.), and carboplatin (250 mg/m(2) i.a.). Chemoembolization with mitoxantrone (10 mg/m(2)) plus ethiodized oil was performed immediately after this treatment, followed by gelatin powder. Fourteen patients entered the study and were evaluable for side effects. Main patient characteristics were: males 13, females 1; median age 65 yr (range 45-75); stage TNM II-III 10, IVA 4; Childs' A 8, Childs' B 6; elevated baseline alpha-fetoprotein, 11; cirrhosis 14. No drug-related deaths have been observed. Ten patients were able to complete the program. The reasons for discontinuing treatment were worsening of liver functions in 3 cases and grade IV neutropenia in 1 patient. Eight patients had grade I-II pain and 10 patients had grade I-II fever. In conclusion the study demonstrated that chemoembolization plus i.a. chemotherapy is feasible in patients with hepatocellular carcinoma in cirrhosis and deserves further investigation.

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: A case-control study

BACKGROUND & AIMS: Viral genotypes have been associated with different severity and outcome of hepatitis C virus (HCV)-related liver disease. The aim of this study was to determine whether HCV genotypes may influence the cirrhosis-related risk of the development of hepatocellular carcinoma (HCC). METHODS: Three groups of patients were studied: 593 patients with chronic hepatitis, 166 patients with HCC and cirrhosis, and 219 patients with cirrhosis but without HCC. A cross- sectional study of frequency distribution and a case-control analysis were performed. HCV genotypes were detected according to Okamoto. RESULTS: HCV type 1b infection was more prevalent among patients with HCC compared with patients with cirrhosis but without HCC (P < 0.01) and chronic hepatitis (P < 0.001). Age, male sex, and HCV type 1b significantly influenced the risk of cancer in cirrhosis by univariate analysis. A pairwise comparison performed on 162 patients with HCC and an equal number of patients with cirrhosis matched by age, sex, and Child's class showed that HCV type 1b was independently associated with HCC (odds ratio, 1.7; P = 0.026). CONCLUSIONS: HCV type 1b is overrepresented in patients with cirrhosis and HCC and significantly influences the risk of HCC in cirrhosis, independent of sex, age, and Child's class. (Gastroenterology 1996 Jul;111(1):199-205)

Liver transplantation for small hepatocellular carcinoma in cirrhosis: Report of the milan prospective trial: [formula omitted] Liver Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy

Liver transplantation for small hepatocellular carcinoma in cirrhosis: Report of the milan prospective trial: [formula omitted] Liver Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy

Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: A prospective study

Background/Aims : In humans, the role of liver cell dysplasia as a preneoplastic lesion is still debated. A prospective, long-term, multicenter study was performed to establish whether liver cell dysplasia in cirrhosis is associated with an increased risk for hepatocellular carcinoma (HCC). Methods : A cohort of 307 consecutive patients in whom liver cirrhosis was diagnosed by histology was investigated for development of HCC at 6-month intervals by ultrasonography and determination of α-fetoprotein levels. Results : At enrollment, liver cell dysplasia was found in 75 patients (24%) and in 53% ( P < 0.01) of those positive for hepatitis B surface antigen (HBsAg). After a mean follow-up of 46 months, HCC was detected in 45 cases, and it was significantly more frequent in patients with liver cell dysplasia ( P < 0.01) and HBsAg-serum positivity ( P < 0.01). Multivariate analysis showed that liver cell dysplasia was the most important risk factor correlated with HCC development. HBsAg positivity and age over 60 years were also independent risk factors for HCC. Conclusions : These results indicate that liver cell dysplasia is a major risk factor for HCC, and it should be looked for carefully by pathologists in liver biopsy specimens to identify patients requiring more intensive observation.

Comparable frequency of hepatocellular carcinoma in cirrhosis of different aetiology

Objective: To evaluate by multivariate analysis whether the risk of hepatocellular carcinoma (HCC) varies in cirrhosis of different aetiology. Design: Cohort study of patients monitored every 6 months by laboratory tests and ultrasonography. Setting: Three northern Italian hospitals. Patients: A total of 396 patients (285 men and 111 women; median age, 58 years) with cirrhosis (253 with Child's class A and 143 class B or C) attributable to alcohol abuse, chronic infection by hepatitis B or non-A non-B virus (hepatitis C virus in 79% of patients) and iron overload due to genetic haemochromatosis, were followed for 1–245 months (median, 50 months). Methods: Cox's regression model was used to evaluate sex, age, Child's class, and aetiology of cirrhosis as independent risk factors for HCC; interactions between aetiologic factors were also considered. Results: During follow-up, 143 patients died and 63 developed HCC. The cumulative probability of remaining free of HCC was 90, 80 and 68% at 2, 6 and 10 years. Age 58 years or more (hazard ratio, 4.26 versus age < 58 years; P< 0.001) and Child's class B or C (hazard ratio, 1.81 versus Child's class A; P<0.05) increased the risk of HCC. Conclusion: The aetiology of cirrhosis, when corrected for age, sex and the severity of cirrhosis, did not significantly affect the risk of HCC development.

Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study

Patients with cirrhosis have a high risk of hepatocellular carcinoma (HCC) but it is unclear how the etiology of liver disease influences tumor development. The authors evaluated hepatitis B and C virus (HBV, HCV) infection in cirrhosis in relation to the risk of HCC. Two hundred and ninety consecutive cirrhotic patients were followed prospectively with periodic ultrasound examination. At entry, patients were tested for markers of HBV and HCV to assess relation to tumor development during follow-up. Twenty and five-tenths percent of patients were hepatitis B surface antigen (HBsAg) positive and 68.9% were positive for HCV antibodies. Previous alcohol abuse was present in 26.2%. During follow-up (46.3 +/- 21.4 months), HCC developed in 32 patients (11.0%) (annual incidence approximately 3%) including 19.6% of HBsAg-positive patients, 12.2% of HCV antibody positive patients and 14.4% of patients with a history of alcohol abuse. The highest rate of HCC was in patients with dual HBsAg and anti-HCV positivity with or without previous alcohol abuse, whereas the lowest incidence (0%) was in cases without risk factors. By univariate analysis, age older than 59 years (P < 0.005), longer duration of cirrhosis (P < 0.005), serum alpha-fetoprotein levels higher than 20 ng/ml (P < 0.05), and dual HBsAg and HCV positivity (P < 0.02) appeared to be associated with HCC. By multivariate analysis, age (P < 0.01), positivity for HBsAg and HCV antibodies (P < 0.05), male sex (P < 0.05), and previous alcohol abuse (P < 0.08) were independently related to tumor appearance. These results, although confirming that male sex and previous alcohol abuse are risk factors for hepatocellular carcinoma in cirrhosis, indicate that concurrent hepatitis B and C virus infection determines the highest risk of developing hepatocellular carcinoma.

Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study

Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study

Screening for hepatocellular carcinoma in patients with Child's A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein

One hundred and forty-seven patients with Child's A cirrhosis and no evidence of hepatocellular carcinoma were followed up in an 8-year prospective surveillance program with testing by ultrasound and alphafetoprotein every 6 months. Eighteen of 147 patients were HBsAg positive. Anti-hepatitis C virus antibodies were found in 103 out of 133 cases tested. Sixteen patients had a history of heavy drinking. Thirty hepatocellular carcinomas were detected during follow up. At the time of diagnosis, ultrasound detected focal lesions in all the patients whereas alphafetoprotein was below diagnostic levels. The hepatocellular carcinoma was single in 26 patients and multiple in four. The overall 8-year cumulative tumor-free rate was 69% (95% confidence interval = 58-73). The yearly hepatocellular carcinoma incidence from 1985 to 1992 was respectively 2%, 1.5%, 2%, 3%, 5%, 4.8%, 7% and 10%. The initial value of AFP > 50 ng/ml and < 400 ng/ml was significantly related to the development of hepatocellular carcinoma. This series shows that the cumulative incidence of hepatocellular carcinoma in cirrhosis in Italy is higher than previously reported, but lower than that observed in Asiatic areas. A 6-month interval for ultrasound is reasonable to detect treatable tumors. Alphafetoprotein has no value for early diagnosis, although its intermediate values (> 50 and < 400 ng/ml) may indicate the presence of undetectable cancer which will appear during the follow up, and suggests that ultrasound should be employed more frequently in patients with these values.

A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis

To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that α-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, α-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody–positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection. (HEPATOLOGY 1993;18:47–53).

A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis

To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that alpha-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, alpha-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody-positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection.

Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival.

We analyzed the growth pattern of tumor masses and the survival of 39 asymptomatic Italian patients with a total of 59 small (less than or equal to 5 cm in diameter) hepatocellular carcinomas arising from cirrhosis. The total length of the observation period ranged from 90 to 962 days, with an average of 364 +/- 229 (mean +/- S.D.). Doubling time ranged from 27.2 to 605.6 days (mean +/- S.D., 204.2 +/- 135; median = 171.6 days). Three different growth patterns were recognized: (a) tumors with no or very slow initial growth pattern (doubling time greater than 200 days), 10 cases (37%); (b) tumors with declining growth rate over time, 9 cases (33.4%); and (c) tumors with almost constant growth rate, 8 cases (29.6%). Using the stepwise discriminant analysis, we found a score based on albumin, alcohol intake, number of nodules, echo pattern and histological type that allowed a correct prediction of short doubling time (less than or equal to 150 days) in 55.6%, medium doubling time (151 to 300 days) in 60% and long doubling time (greater than 300 days) in 100% of cases. The estimated survival rate of the 39 patients, calculated by the Kaplan-Meier method was 81% at 1 yr, 55.7% at 2 yr and 21% at 3 yr. Stepwise discriminant analysis showed that a score based on sex, HBsAg status, alcohol consumption, ascites, gamma-glutamyltranspeptidase, prothrombin time, Child-Pugh class and all the sonographical parameters could predict 2-yr survival in 100% of cases. We conclude that great variability of growth patterns exists among and within small hepatocellular carcinomas. Prediction of subsequent growth rate is unreliable in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Space-occupying lesions of the liver detected by ultrasonography and their relation to hepatocellular carcinoma in cirrhosis.

Fifty-four patients with cirrhosis, found to have a space-occupying lesion in the liver by ultrasound (US), underwent US-assisted biopsy of the lesion and were then followed prospectively to define outcome and survival. Histologic examination revealed hepatocellular carcinoma in 26 patients, while five had liver cell dysplasia without hepatocellular carcinoma and 23 had no evidence of tumor or of dysplasia. All five patients with an initial diagnosis of dysplasia developed hepatocellular carcinoma during follow-up and their survival curve was similar to that of patients with liver cancer and significantly worse than that of patients without dysplasia or tumor. There were five false-negative cases of hepatocellular carcinoma among the patients with negative histology. Overall, US-assisted liver biopsy diagnosed malignancy with a sensitivity of 72%, which increased to 86% when dysplasia was considered a pre-neoplastic lesion.

Anti-HCV positive hepatocellular carcinoma in cirrhosis: Prevalence, risk factors and clinical features

Recent reports indicate that hepatitis C virus (HCV) may play a role in the pathogenesis of hepatocellular carcinoma in cirrhotics. Using an ELISA test, we evaluated the prevalence of anti-HCV antibodies in 97 patients with hepatocellular carcinoma (HCC) in cirrhosis and in a group of 223 patients, including: 49 patients with HBsAg-positive chronic liver disease (CLD), 42 with alcoholic CLD, 110 with cryptogenic CLD and 22 with post-transfusional HBsAg-negative CLD. All diagnoses were histologically confirmed. Overall, anti-HCV-positive HCC were 64% of the total, with no statistically significant difference with respect to CLD (60.9%). The prevalence of anti-HCV was higher in cryptogenic HCC (80%) than in HBsAg-positive (60%) or alcoholic HCC (42.8%) ( p < 0.005). When HCC and cirrhosis of similar putative etiology were considered, anti-HCV prevalence was significantly higher in HCC than in cirrhosis only in the groups of patients with alcoholic liver damage (60% in HCC vs. 38% in cirrhosis, p < 0.005). In HBsAg-positive patients, anti-HCV prevalence was twice as high in HCC than in CLD, but the difference was not statistically significant. Overall, anti-HCV prevalence in HCC was significantly higher than in alcoholic or HBsAg-positive CLD ( p < 0.001 and p < 0.01, respectively) but lower than in cryptogenic CLD ( p < 0.001). Association between anti-HCV and anti-HBc was significantly more prevalent in patients with CLD than in those with HCC. From the clinical point of view, multifocal lesions and lack of a history of previous liver disease were more frequent in anti-HCV-positive HCC ( p < 0.05) than in HBsAg-positive or alcoholic patients. Anti-HCV-positive HCC had a significantly worse prognosis ( p < 0.005 with the Generalized Wilcoxon-Breslow test), when survival in the different subgroups was examined with life table analysis. No statistically significant differences were observed with respect to the remaining parameters considered. In conclusion, HCV infection appears to be a frequent event in HCC and CLD, particularly in patients with cryptogenic liver disease but, with the exception of patients with alcoholic liver damage, the prevalence of anti-HCV appears to be similar in HCC and cirrhosis. This could indicate that the infection plays an important role only in specific subgroups of HCC patients. Anti-HCV-positive HCC is frequently diagnosed in a more advanced stage and has a worse prognosis but, since the clinical history of this subgroup of patients frequently makes its debut with HCC, in our opinion the prognosis is worse due to late diagnosis.

Liver cell dysplasia and risk of hepatocellular carcinoma in cirrhosis: a preliminary report.

In humans the premalignant nature of liver cell dysplasia is still controversial. Only prospective studies can establish whether patients with liver cell dysplasia have an increased risk of developing hepatocellular carcinoma. In 1984 we started a long term prospective study of a cohort of patients with cirrhosis of the liver. We report here the results of an interim analysis