Luisa Benvegnù

Sustained virological response to interferon-α is associated with improved outcome in HCV-related cirrhosis: A retrospective study†‡

The effect of achieving a sustained virological response (SVR) following interferon‐α (IFNα) treatment on the clinical outcomes of patients with HCV‐related cirrhosis is unknown. In an attempt to assess the risk of liver‐related complications, HCC and liver‐related mortality in patients with cirrhosis according to the response to IFNα treatment, a retrospective database was developed including all consecutive patients with HCV‐related, histologically proven cirrhosis treated with IFNα monotherapy between January 1992 and December 1997. SVR was an undetectable serum HCV‐RNA by PCR 24 weeks after IFNα discontinuation. HCC was assessed by ultrasound every 6 months. Independent predictors of all outcomes were assessed by Cox regression analysis. Of 920 patients, 124 (13.5%) were classified as achieving a SVR. During a mean follow‐up of 96.1 months (range: 6‐167) the incidence rates per 100 person‐years of liver‐related complications, HCC and liver‐related death were 0, 0.66, and 0.19 among SVR and 1.88, 2.10, and 1.44 among non‐SVR (P < 0.001 by log‐rank test). Multivariate analyses found that non‐SVR was associated with a higher risk of liver‐related complications (hazard ratio, HR, not applicable), HCC (HR 2.59; 95% CI 1.13‐5.97) and liver‐related mortality (HR 6.97; 95% CI 1.71‐28.42) as compared to SVR. Conclusion: Thus, in patients with HCV‐related, histologically proven cirrhosis, achievement of a SVR after IFNα therapy was associated with a reduction of liver‐related mortality lowering both the risk of complications and HCC development. Irrespective of SVR achievement, all patients should continue surveillance because the risk of occurrence of HCC was not entirely avoided. (HEPATOLOGY 2007;45:579–587.)

Management of hepatitis C.

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide and represents a major public health problem. Its epidemiology has been changing during the last decade and great progress has been made in the development of new diagnostic tests and treatment strategies thanks to the combined efforts of the academic and industry-sponsored research. However, there are still a number of issues that have not yet been completely solved, particularly in relation to the full understanding of the pathogenesis of liver disease and mechanisms leading to chronicity and to severe end stage. Therapy has improved in recent years and eradication of hepatitis C virus (HCV) by treatment is a reality in many chronically infected patients, but the issue of a substantial number of non-responders is still unsolved. This review addresses the main recent developments in the field of basic and clinical research on HCV, with particular reference to the clinical management of acute and chronic hepatitis C.

Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications

Background and aims: The natural history of initially compensated cirrhosis due to hepatitis B (HBV) or hepatitis C (HCV) virus is only partially defined. We have investigated morbidity and mortality rates and the hierarchy of complications in compensated viral cirrhosis over a long follow up period. Patients and Methods: A cohort of Italian patients with initially compensated cirrhosis of viral aetiology were followed up at six monthly intervals with laboratory tests to identify major complications (ascites, gastrointestinal bleeding, portal-systemic encephalopathy, hepatocellular carcinoma) and to assess the progression of Child’s stage and mortality rate due to liver related causes. Results: Between 1986 and 1996, 312 patients (43 HBV positive, 254 HCV positive, and 15 HBV and HCV coinfected) were included. During a median follow up of 93 (range 14–194) months, 102 (32.6%) patients developed at least one complication (HCV positive 31.1%; HBV positive 34.8%; HBV and HCV coinfected 53.3%). Overall, the most frequent complication was hepatocellular carcinoma which occurred in 65 (20.8%) cases, followed by ascites (61 cases, 19.5%), gastrointestinal bleeding (14 cases, 4.5%), and portal-systemic encephalopathy (six cases, 1.9%). Progression of Child’s stage was observed in 62 patients (19.8%). Death from liver disease occurred in 58 (18.6%) cases and in 70.7% this was due to hepatocellular carcinoma. Hepatocellular carcinoma was the first complication to develop in 59 cases and represented the most frequent first complication in both HCV and HBV/ HCV related cirrhosis. Conclusions: These results indicate significant morbidity and mortality during the first decade after diagnosis of compensated cirrhosis due to HBV and/or HCV, and identify hepatocellular carcinoma as the most frequent and life threatening complication, particularly in HCV positive cases.

Natural history of hepatitis C

Ten years after the discovery of the hepatitis C virus (HCV) and its association with NANB hepatitis as a major cause of chronic liver disease worldwide, our knowledge of the natural history of hepatitis C is still limited. The asymptomatic course of the disease in most patients, its slow and silent progression and heterogeneous outcome and the widespread use of interferon therapy during the past decade explain why many questions are still unsolved. The changing epidemiological pattern of HCV and the significant contribution of several cofactors to the severity of liver disease also complicate the development of a general model describing the natural history of hepatitis C. Available data indicate that HCV infection may resolve without any clinical signs of liver disease in individuals exposed to low dose inoculum and that these cases may develop T cell immunity even in the absence of anti-HCV seroconversion. Rates of complete biochemical and virological resolution of acute hepatitis C range between 10 and 50%, and are probably affected by the route of infection, size and type of inoculum and acute phase clinical features. Chronic HCV infection may develop with or without ALT abnormalities and with or without chronic inflammation and increasing fibrosis in the liver. Studies conducted in patients who acquired hepatitis C by blood transfusion 15-25 years ago indicate that 20-30% of them have now progressed to cirrhosis, including 5-10% with end stage liver disease and 4-8% who died of liver-related causes. Similar studies conducted in patients infected by other routes have shown a more benign course of hepatitis C, with little evidence of cirrhosis and no liver-related mortality during the first two decades. Outcomes after longer follow-up need to be assessed. In patients presenting with chronic hepatitis C, fibrosis progression is extremely variable over time and can be partially predicted by the age at infection, disease duration, liver histologic activity and stage of fibrosis and by the ALT profile. However, it is often difficult to predict clinical outcomes in individual cases. In patients who have developed cirrhosis, the 5-year risk of decompensation is between 15 and 20% and that of hepatocellular carcinoma around 10%. Several variables have been shown to influence the natural course of shown C, the most significant being age at infection, alcohol consumption and coinfection with HBV and HIV Studies are being performed to assess the role of host genetics. Viral factors, such as the HCV type and load, seem to have inconsistent or marginal effects.

Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience).

OBJECTIVES:Surveillance of cirrhotic patients for early detection of hepatocellular carcinoma, based on ultrasonography and α1-fetoprotein determination, is a recommended practice. However, it has not been proved that this procedure can improve patient survival.METHODS:We conducted a multicenter retrospective study on 1051 consecutive patients with hepatocellular carcinoma. The criteria for eligibility were presence of underlying cirrhosis, and description of cancer stage and modalities of its diagnosis. Among 821 patients fulfilling these criteria, the tumor was detected during semiannual surveillance in 215 individuals (group 1), during annual surveillance in 155 (group 2), and as a result of symptoms or incidentally in 451 (group 3). Survival of patients under surveillance was corrected for lead time.RESULTS:Cancer stage was similar in groups 1 and 2 and was less advanced than in group 3 (p < 0.001). The frequency of ablative treatments or chemoembolization was similar in groups 1 and 2 and was greater than in group 3 (p < 0.001). Both surveillance programs doubled the prevalence of potential candidates for liver transplantation (68.5% and 62.5%) with respect to group 3 (32.3%, p < 0.001). However, only 15 patients underwent transplantation. In groups 1 and 2, the 5-yr survival was equivalent and was greater than in group 3 (p < 0.001). By segregating patients according to severity of cirrhosis, the benefit was confined to compensated cirrhosis (adjusted relative risk of death for patients under surveillance: 0.59 [95% CI = 0.45–0.78]).CONCLUSIONS:Semiannual and annual surveillance equally improve the survival of cirrhotic patients with hepatocellular carcinoma and greatly increase the amenability rate to liver transplantation. When access to liver transplantation is limited, this benefit is restricted to patients with a good cirrhosis-related prognosis.

Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?

BACKGROUND:The clinical usefulness of α-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable.OBJECTIVES:To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype.METHODS:A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor–nodes–metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity.RESULTS:Patients were divided into three AFP groups: normal (<20 ng/mL) [46%], elevated (21–400 ng/mL) [36%], and diagnostic (>400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (P = 0.0056), pain (P = 0.0025), Child-Pugh score (P = 0.001), tumor size, Okudas and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1–4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001).CONCLUSION:The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.

Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival

BACKGROUND & AIMS The current guidelines recommend the surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on liver ultrasonography repetition at either 6 or 12 month intervals, since there is no compelling evidence of superiority of the more stringent program. This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance. METHODS We analyzed the clinical records of 649 HCC patients in Child-Pugh class A or B, observed in ITA.LI.CA centers. HCC was detected in 510 patients submitted to semiannual surveillance (Group 1) and in 139 submitted to annual surveillance (Group 2). In Group 1 the survival was presented as observed and corrected for the lead time. RESULTS The cancer stage was less severe in Group 1 than in Group 2 (p<0.001), with more single tiny (2 cm) and less advanced tumors. Treatment applicability was improved by the semiannual program (p=0.020). The median observed survival was 45 months (95% CI 40.0-50.0) in Group 1 and 30 months (95% CI 24.0-36.0) in Group 2 (p=0.001). The median corrected survival of Group 1 was 40.3 months (95% CI 34.9-45.7) (p=0.028 with respect to the observed survival of Group 2). Age, platelet count, alpha-fetoprotein, Child-Pugh class, cancer stage, and hepatocellular carcinoma treatment were independent prognostic factors. CONCLUSIONS Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis.

Prevalence of liver disease in a population of asymptomatic persons with hepatitis C virus infection

Context Many persons infected with hepatitis C virus (HCV) are asymptomatic. The extent of liver disease in these persons is unclear. Contribution The researchers tested 4820 apparently healthy persons in Italy for hepatitis C virus. Among the 116 (2.4%) who tested positive, 85 were viremic; only about half of these 85 patients had elevated alanine aminotransferase (ALT) levels. Liver biopsy showed substantial inflammation or fibrosis in 19% of persons with normal ALT levels and 61% of persons with abnormal ALT levels. Implications The substantial prevalence of abnormal liver histology among asymptomatic persons is a provocative but incomplete rationale for screening for HCV. The prevalence of infection and the effectiveness of treatment are also important considerations. The Editors Although new hepatitis C virus (HCV) infections have declined during the past decade in most developed countries (1), hepatitis C remains a major health problem because of the many persons infected before serologic testing became available (2, 3). Many persons with HCV infection are asymptomatic and unaware that they are infected. While it is clear that HCV contributes greatly to end-stage liver disease, the natural history of hepatitis C in asymptomatic individuals is poorly defined. Published studies indicate that the natural history of hepatitis C is heterogeneous. Several factors, including age at infection, alcohol use, and co-infection with hepatitis B virus or HIV, increase the risk for cirrhosis (4-8). Independent of these cofactors, prognosis is related to hepatic histopathology, particularly the type and amount of liver necroinflammation and fibrosis (9-11). Our understanding of the histology of hepatitis C in asymptomatic persons comes mainly from studies of blood donors (a selected population) (12-14). We report an investigation of the prevalence, histologic activity, and stage of HCV infection in 4820 otherwise apparently healthy adults living in northeastern Italy. Methods Patients We tested for serum anti-HCV in 4820 adults (2132 men and 2688 women; age range, 16 to 60 years) who were undergoing a screening program for cardiovascular risk factors. To be eligible for this program, persons had to be free of acute or chronic illness (based on history and clinical symptoms) at the time of evaluation. Telecom Italy proposed and promoted the screening program to employees and their relatives. Participation was voluntary. Participants lived in one of three regions (Veneto, Trentino-Alto-Adige, and Friuli-Venezia-Giulia) in northeastern Italy and included a wide range of socioeconomic strata (from employees in lower positions to senior managers and their relatives). All 4820 persons (1210 employees and 3610 relatives) gave written informed consent and underwent clinical evaluation and testing for anti-HCV by enzyme-linked immunosorbent assay (ELISA) (Ortho Diagnostic Systems, Raritan, New Jersey) at the initial visit. Within 1 month, we retested persons who were positive for anti-HCV by ELISA. Serum that was confirmed to be HCV positive was tested for HCV RNA by polymerase chain reaction (PCR) (Amplicor HCV Monitor test, Roche Diagnostics, Indianapolis, Indiana). We retested serum for HCV RNA after 1 and 3 months in confirmed anti-HCVpositive persons whose initial test results for HCV RNA had been negative. We monitored serum alanine aminotransferase (ALT) levels 1, 3, 6, and 12 months after anti-HCV detection. We proposed liver biopsy for all viremic persons. These biopsies were done 6 to 14 months after detection of anti-HCV; patients provided informed consent. Liver biopsy specimens were evaluated according to the METAVIR scoring system (15). We classified patients with METAVIR scores of F2 and higher or A2 and higher as having significant liver disease according to international guidelines (16). Statistical Analysis Prevalences of HCV infection and of liver disease were compared by using the Fisher exact test for 2 2 tables. The chi-square test for linear trend was used to compare prevalences in age subgroups. Role of the Funding Source The study protocol was developed by a Scientific Committee of the Italian National Research Council (CNR), approved by a National Ethical Committee, and directly funded by the Italian National Research Council. The Italian National Research Council had no role in the collection, analysis, and reporting of the study or in the decision to publish the manuscript. Results Prevalence of HCV Infection in the Screened Population Of the 4820 persons tested, 116 (2.4% [CI, 1.97% to 2.84%]) were repeatedly positive for anti-HCV by ELISA and 12 additional persons were initially positive but were negative on repeated testing. Samples confirmed to be anti-HCV positive were tested for HCV RNA; 75 of these were positive. The 41 persons who were initially positive for anti-HCV but negative for HCV RNA were tested for serum HCV RNA 1 and 3 months after anti-HCV detection; 10 were positive in both (n = 8) or one (n = 2) follow-up test. Thus, 85 of 116 anti-HCVpositive persons (73.3%), or 85 of 4820 screened individuals (1.76 % [CI, 1.39% to 2.14%]) were positive for HCV RNA. Among the 85 HCV RNApositive individuals, ALT levels were normal (<50 U/L) at all times (at 0, 1, 3, 6, and 12 months) in 39 persons (46%), elevated at all times in 37 persons (43.5%), and abnormal at least once in 9 patients (10.5%). The 10 persons with intermittent HCV RNA positivity had persistently normal ALT levels during follow-up. Liver Histology in HCV-Infected Persons Seventy-eight of the 85 persons who were positive for HCV RNA had liver biopsies; these 78 patients included 32 of 39 persons with persistently normal ALT levels and all 46 persons with elevated ALT levels. The Figure summarizes the histopathologic characteristics of the 78 HCV-positive persons according to the ALT profile during the observation period. Overall, 52% of patients with elevated ALT levels and 19% of patients with normal ALT levels had significant fibrosis (F2 to F4), whereas 24% of patients with elevated ALT levels and none with normal ALT levels had significant necroinflammatory activity (A2 to A3). Thus, on the basis of a fibrosis score of 2 or higher or an activity score of 2 or higher, moderate to severe chronic hepatitis was seen in 28 of 46 (61% [CI, 45.4% to 74.9%]) patients with elevated ALT levels and in 6 of 32 (19% [CI, 7.21% to 36.4%]) patients with normal ALT levels (P < 0.001). Both mean and peak ALT values during the 12-month follow-up period correlated with activity and fibrosis stage (Table). The percentage of patients with significant activity or fibrosis increased with increasing ALT levels (data not shown). Figure. Histologic activity and fibrosis stage of the 78 persons with normal or elevated alanine aminotransferase levels who were positive for hepatitis C virus. Table. Liver Histology during the 12-Month Follow-up Period in 78 Hepatitis C VirusPositive Persons Prevalence of HCV Infection and Liver Disease by Age Prevalence of HCV RNA positivity increased with age: 0.67% (CI, 0.23% to 1.57%) in persons age 16 to 30 years, 1.4% (CI, 0.93% to 2.08%) in persons age 31 to 45 years, and 2.4% (CI, 1.8% to 3.2%) in persons age 46 to 60 years (P = 0.003). The percentage of persons with persistently normal ALT levels was similar in the three age groups, but severity of liver disease increased with age. The prevalence of significant fibrosis (F2) was 20% in the persons age 16 to 30 years and 48% in the persons age 46 to 60 years. When only patients with abnormal ALT levels were considered, the corresponding figures were 33% in persons age 16 to 30 years, 50% in the persons age 31 to 45 years, and 79% in the persons age 46 to 60 years. HCV Genotypes Among the 85 persons positive for HCV RNA, 52 (61.2%) were infected with HCV genotype 1b, 5 (5.8%) with genotype 1a, 20 (23.5%) with genotype 2a/2c, and 8 (9.4%) with genotype 3. Four of 5 patients age 16 to 30 years were infected with genotype 3, and the fifth was infected with genotype 1a. Genotype in persons age 31 to 45 years and 46 to 60 years did not differ significantly. The HCV genotypes were not significantly associated with ALT levels or histologic features after adjustment for age (data not shown). Discussion It has been difficult to estimate precisely how many asymptomatic HCV-infected persons are at significant risk for progressive liver disease. This is a result of the limited available information on the actual burden of HCV in the general population and uncertainty about the natural course of HCV infection in asymptomatic individuals (16). Previous studies mainly considered blood donors screened for anti-HCV and rarely reported systematic data on liver histology. Our survey was conducted in a less highly selected population and might therefore better represent the burden of HCV in the general population. Limitations of our study include the uncertain generalizability to other geographic areas, the inclusion of only working adults and their relatives, and the lack of detailed information on risk factors in the screened population and of cofactors known to influence hepatitis C progression (use of alcohol or drugs; co-infection with hepatitis B virus or HIV) in the HCV-positive persons. Our data may underestimate the prevalence of HCV because of a healthy worker effect. Despite these limitations, our data indicate that progressive liver disease can be detected in a substantial proportion of apparently healthy, asymptomatic persons with HCV infection. Of note, almost 40% of individuals positive for HCV RNA, representing 0.70% of the general population cohort screened, had active inflammatory lesions or advanced fibrosis (as shown by liver biopsy results). These histologic features are considered the hallmark of progressive HCV infection and indications for antiviral therapies (16). Our findings would suggest that broader screening for HCV in the general population might be indi

Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma

Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score⩽1) was associated to lower MIB-1 labelling index, compared to cases with SCCA score ⩾2 (mean±s.d.: 2%±2.4 vs 7.5%±10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G351 to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score⩽1) was associated to lower MIB-1 labelling index, compared to cases with SCCA score ⩾2 (mean±s.d.: 2%±2.4 vs 7.5%±10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G351 to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.

Surveillance for hepatocellular carcinoma in elderly italian patients with cirrhosis: Effects on cancer staging and patient survival

OBJECTIVES:Surveillance of cirrhotic individuals for early detection of HCC, based on ultrasonography (US) and α1-fetoprotein (AFP) determination, is a recommended practice currently applied also to elderly patients. However, several age-related factors may jeopardize the results of surveillance in these patients. Aim of the study was to evaluate the benefit of surveillance for HCC in elderly individuals.METHODS:Multicenter retrospective study on 1,277 consecutive patients with HCC. The inclusion criteria were: underlying chronic liver disease, description of cancer stage, and modalities of its diagnosis. Among the 1,037 patients fulfilling these criteria, 363 aged ≥70 yr were considered.RESULTS:The tumor was detected during surveillance, based on US and AFP performed every 6–12 months, in 158 individuals (group 1), incidentally in 138 (group 2) and because of symptoms in 67 (group 3). Surveillance reduced the risk of dealing with an advanced cancer (odds ratio (95% Confidence Interval): 0.18 (0.09–0.37) vs group 3, and 0.29 (0.17–0.49) vs group 2). The frequency of effective treatments decreased from group 1 to group 3 (73%, 57%, and 31%, respectively). The main cause of death was HCC progression. The survival corrected for the lead time of group 1 (median: 24 months) was significantly better than the crude survival of group 3 (7 months; p= 0.003) and barely better than that of group 2 (21 months). The latter also showed a better prognosis with respect to group 3 (p= 0.018).CONCLUSIONS:Surveillance for HCC improves the survival of elderly cirrhotic patients by expanding the percentage of cancers amenable to effective treatments.