Interferon Alpha-2a Treatment for Post-Uveitic Refractory Macular Edema.

Purpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME).Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months.Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8-24] months with a follow-up of 17[10-38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] µm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] µm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events.Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.

Aqueous tap and rapid diagnosis of cytomegalovirus anterior uveitis: the Reggio Emilia experience.

PURPOSE: The diagnosis of cytomegalovirus (CMV) anterior uveitis in immunocompetent patients requires confirmation by polymerase chain reaction (PCR) analysis and/or intraocular antibody index (AI) assay. In this study, we analyzed the different contributions of PCR and AI to CMV diagnosis by performing one single aqueous tap. METHODS: A retrospective chart review was conducted of HIV-negative patients attending the Ocular Immunology Unit of Azienda Unità Sanitaria Locale - IRCCS, Reggio Emilia, Italy, from March 2015 to April 2018 with a diagnosis of hypertensive anterior granulomatous uveitis compatible with suspected CMV etiology. Diagnosis was confirmed by real-time PCR (RT-PCR) and intraocular antibody production against CMV on aqueous humor samples. Clinical features were compared to antibody titer and diagnostic delay. RESULTS: Twenty-three patients with suspected CMV uveitis (13 males, 10 females, mean age 48 ± 16 years) were included in the analysis. AI was positive in 20/23 (87%) samples, and PCR tested positive in 9/23 (39%). By combining both tests, the sensitivity was 100%. Median diagnostic delay was 29 months (IQR 9-107). Diagnostic delay and antibody titer were significantly associated with glaucoma (r = 0.714, p < 0.0001; r = 0.476, p = 0.02, respectively). CONCLUSIONS: Our data suggest that to improve the diagnostic accuracy of CMV anterior uveitis, PCR and AI are both useful and complimentary. In our series, AI was the most sensitive diagnostic tool. One single aqueous tap is sufficient to achieve 100% sensitivity in CMV diagnosis. Early diagnosis is necessary to prevent the development of glaucoma.

Clinical features and outcomes of hepatocellular carcinoma in Caucasian cirrhotic patients on long-term analogue therapy for hepatitis B.

BACKGROUND: Long-term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)-related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma (HCC) development. AIMS: To define the clinical features and outcomes of HCC in long-term NUC-treated HBV patients. METHODS: All HCCs developing between 2005 and 2016 in NUC-treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied. RESULTS: Seventy-six HCC patients were included. Median age was 67 (40-83) years, 84% males, 96% Caucasian, 95% HBeAg-negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1-3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6-57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first-line treatment, in 3 after the second-line treatment, in 2 after the third-line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7-144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3-53) months, and the cumulative 5-year liver-related survival was 74%. CONCLUSIONS: HCCs developing in patients under long-term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5-year survival rates.

Transarterial embolization with microspheres in the treatment of monofocal HCC.

BACKGROUND: Transarterial embolization using one permanent embolic agent alone enhances tumour ischaemia and spares patients with hepatocellular carcinoma form toxic chemotherapeutic drugs. PURPOSE: We assessed feasibility, tolerability and efficacy of transarterial embolization with microspheres in patients with a single node hepatocellular carcinoma. MATERIALS AND METHODS: Eighteen consecutive patients with compensated cirrhosis, hypervascularized single hepatocellular carcinoma, in whom liver transplantation was indicated (no.=3), or excluded from radical therapies (no.=15), received selective transarterial embolization with microspheres. Treatment was repeated every other month until complete devascularitazion was demonstrated by computed tomography, for a maximum of 3 cycles. RESULTS: Fifty transarterial embolization courses (mean: 2.8 courses, range 1-6) were administered, corresponding to a 100% applicability rates. Initial complete response was achieved in 16 (89%) patients and confirmed by histology in 2 transplanted patients. During 21-month follow-up (range 8-36), hepatocellular carcinoma recurred in 10 (62%) patients who achieved initial complete response, and de novo tumour nodes developed in 10 (56%). No patient required analgesics and none had liver function deteriorated following transarterial embolization. CONCLUSIONS: Transarterial embolization is a well-tolerated treatment for patients with early or intermediate hepatocellular carcinoma who are not suitable for radical treatment or await liver transplantation, but it allows to achieve a sustained complete response in a minority of patients.

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success. AIM: We evaluated plasma chromogranin A (CgA) as a marker of HCC. PATIENTS: CgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls. METHODS: CgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy). RESULTS: CgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21-145.9)U/L vs. 15.3 (10.9-29.25)U/L, p<0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p<0.005). CgA values significantly correlated with AFP levels (r(s)=0.42, p<0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66-82), with a sensitivity of 70% (CI 50.6-85.2) and a specificity of 67% (CI 55.9-76.3). CONCLUSIONS: Despite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.

Role of transjugular liver biopsy in the diagnostic and therapeutic management of patients with severe liver disease.

PURPOSE: This study sought to assess the diagnostic yield, the impact on treatment and the safety of transjugular liver biopsy. MATERIALS AND METHODS: We reviewed the medical records of 72 patients with severely impaired liver function who underwent transjugular biopsy at our department. Contraindications to percutaneous liver biopsy included thrombocytopenia, severe coagulopathy, marked ascites or a combination of the above. Patients were divided into four groups based on the clinically suspected cause of liver disease. Group 1 included 44 patients (58%) with acute abnormalities of liver function, whereas groups 2, 3 and 4 included patients with chronic abnormalities suspected to be due to infectious cirrhosis (12 patients, 16%), alcoholic cirrhosis (seven patients, 9%) and cirrhosis of unknown origin (13 patients, 17%), respectively. A Quick-Core (Cook, ProAct Ltd., State College, Pennsylvania, USA) needle allowing automated tissue sampling was used for all biopsies. RESULTS: Biopsy specimens were diagnostic in 69 out of 72 patients (91%). Biopsy findings influenced treatment in 34 out of 69 patients (49%). The most significant results were obtained in group 1, where the histological diagnosis differed from clinical suspicion in 25/39 patients. There was only one major complication and four minor complications. The major complication was an arteriovenous and arteriobiliary fistula with haemorrhage and anaemia, which was successfully embolised by the same team of interventional radiologists. CONCLUSIONS: Transjugular liver biopsy proved to be a safe procedure that provided important information for the clinical and therapeutic management of patients in whom treatment would have been either empirical or unfeasible.

Increased expression of vascular endothelial growth factor in small hepatocellular carcinoma.

Vascular endothelial growth factor (VEGF) is involved in both development and progression of several epithelial tumours, but its role in hepatocellular carcinoma (HCC) is unclear. Assessment of liver and blood levels of VEGF may provide further insights on angiogenesis in HCC. Tissue mRNA of VEGF-165, VEGF-189 and their receptor KDR was assessed by a semi-quantitative retro-transcriptase polymerase chain reaction, and expressed as target transcript/beta-actin ratio, in 29 patients with HCC, 26 with cirrhosis and 15 with chronic hepatitis. VEGF-165 was also measured by ELISA in plasma samples obtained from both hepatic and femoral veins in additional 58 patients, including 15 with HCC. The liver expression of mRNA of VEGF-165, VEGF-189 and KDR was higher in HCC than in chronic liver diseases (1.54 +/- 0.89 vs 0.62 +/- 0.47, P < 0.0001; 1.09 +/- 0.65 vs 0.64 +/- 0.54, P = 0.003; 1.30 +/- 1.09 vs 0.69 +/- 0.72, P = 0.014). VEGF-165 was higher in HCC tissue than in extra-tumoural tissues (1.44 +/- 0.31 vs 1.03 +/- 0.21, P = 0.0009) and in the cirrhotic tissue of HCC patients than in HCC-free cirrhosis (1.03 +/- 0.23 vs 0.45 +/- 0.45, P = 0.0002). Tissue VEGF-189 mRNA inversely correlated with tumour size and degree of tumour cell proliferation. The hepatic and femoral vein levels of VEGF-165 protein were significantly higher in HCC patients than in cirrhotic patients (66.7 +/- 57.1 vs 24.2 +/- 16.4 pg/mL, P = 0.0001 and 37.1 +/- 42.2 vs 13.5 +/- 9.6 pg/mL, P = 0.001). There was a gradient of VEGF-165 between hepatic and femoral veins in both HCC and cirrhosis. In conclusion, VEGF appears to be involved in the development of HCC and it could be a predictor of HCC development in patients with cirrhosis.

Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis.

BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Hepatocyte proliferation and risk of hepatocellular carcinoma in cirrhotic patients.

OBJECTIVES: High hepatocyte proliferation has been recently proposed as a risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess whether hepatocyte proliferation is an independent risk factor for HCC when considered together with clinical and demographic characteristics. METHODS: We retrospectively evaluated 97 consecutive patients with a histological diagnosis of cirrhosis and preserved liver function, enrolled in a surveillance program for early diagnosis of HCC. Hepatocyte proliferation was evaluated by flow-cytometric analysis in liver samples collected at the time of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum alpha-fetoprotein (AFP) assays every 6 months. RESULTS: During a mean follow-up of 53 months (range, 12-120 months), 12 patients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5%+/-1.6 in patients who developed HCC and 0.9%+/-0.6 in those who did not (p < 0.0001). By univariate analysis, S-phase fraction 1.8% or higher and AFP higher than 20 ng/ml were the only two variables significantly correlated with the development of HCC (p < 0.0001, p < 0.0001). Multivariate analysis found that both variables were independently associated with HCC development (p < 0.003 and p < 0.005, respectively), with hazard ratios of 8.0 and 7.3 (confidence intervals, 2.1-31.2 and 1.8-29.2). Among patients with high AFP and/or high S-phase fraction, 11 (39%) developed HCC, compared with only one (1%) with a low S-phase fraction and normal AFP, corresponding to HCC yearly incidences of 9.5% and 0.3% (p < 0.00009). CONCLUSIONS: Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surveillance program.

Computed tomographic colonography and conventional colonoscopy for colon diseases: a prospective, blinded study.

OBJECTIVES: Computed tomographic (CT) colonography or virtual colonoscopy is a new diagnostic method for the colon and rectum, developed on the basis of spiral computed axial tomography and employing virtual reality technology. The aim of this study was to determine the sensitivity, specificity, and diagnostic accuracy of CT colonography compared with colonoscopy in a prospective, blinded study in one single institution in Italy. METHODS: Ninety-nine patients randomly selected among those attending the open-access endoscopy unit for diagnostic colonoscopy underwent colonoscopy and spiral CT. The images obtained were transmitted to generate the virtual colonoscopy pictures. A supervisor compared the results with the findings of conventional colonoscopy. RESULTS: CT colonography diagnosed seven of eight tumors, one being missed because the patient had been inadequately prepared. In 28 patients, CT colonography identified 26 polyps of 45 (57.8% sensitivity, 92.6% specificity, 86.7% positive predictive value), regardless of their size. The sensitivity in detecting colonic polyps was 31.8% (7/22) in the first 25 cases and 91.6% (11/12) in the last 20 patients. CT colonography missed one flat adenoma, some angioectasias and colonic lesions because of portal hypertension in one patient, Crohn's disease ulcers in two patients, and ulcerative colitis lesions in three. CONCLUSIONS: CT colonography shows poor sensitivity for identifying colonic polyps and does not always detect neoplastic lesions. Flat lesions are impossible to see by this method.

Acute self-limiting jejunitis as the first manifestation of microscopic polyangiitis associated with Sjogren's disease: report of one case and review of the literature.

We report a case of acute self-limiting ulcerative jejunitis of unknown aetiology in a 72-year-old female patient in which a subsequent diagnosis of microscopic polyangiitis and Sjogren's syndrome was made. All known causes of jejunal ulceration and inflammation were excluded. Previously reported cases of acute self-limiting jejunitis are reviewed and the possibility that acute jejunitis in this patient had been the first manifestation of systemic vasculitis is discussed.

High prevalence of multinodular hepatocellular carcinoma in patients with cirrhosis attributable to multiple risk factors.

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 alpha-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 =.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 <.04; vs. 47%, P <.002; vs. 52%, P <.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.

Granulomatous gastritis presenting as gastric outlet obstruction: a case report.

The clinico-pathologic entity of idiopathic granulomatous gastritis is a form of granulomatous gastritis, distinct from Crohn's disease, sarcoidosis, infections, foreign bodies, malignancy or vasculitis. The case of a 61-year-old female is described who was admitted on account of progressive weight loss, diffuse abdominal pains, post-prandial vomiting. Gastroscopy revealed a pyloric stenosis managed surgically. Pathological examination of the resected stomach showed numerous non-caseating granulomas in the lamina propria. No definite aetiological factor could be detected. A diagnosis of idiopathic granulomatous gastritis was made. She remains well 5 years later and has not developed regional enteritis, sarcoidosis, or any other generalized diseases.

Portal hypertensive gastropathy: reproducibility of a classification, prevalence of elementary lesions, sensitivity and specificity in the diagnosis of cirrhosis of the liver. A NIEC multicentre study. New Italian Endoscopic Club.

OBJECTIVE: To classify elementary endoscopic lesions of portal hypertensive gastropathy, assess their reproducibility, prevalences, sensitivity and specificity in the diagnosis of cirrhosis of the liver. METHODS: 1) A classification of portal hypertensive gastropathy elementary lesions was defined. 2) Thirty-two endoscopists evaluated videotapes of endoscopic examinations of patients with liver cirrhosis to assess beyond-chance agreement (kappa). 3) Fifteen centres enrolled consecutive patients with or without cirrhosis of the liver and recorded portal hypertensive gastropathy pattern according to its location. RESULTS: 1) Four elementary lesions (Mosaic-Like Pattern, Red Point Lesions, Cherry Red Spots, Black-Brown Spots) were identified, and graded. 2) A fair to good beyond-chance agreement was obtained for all 4 lesions. 3) portal hypertensive gastropathy prevalence was higher in patients with cirrhosis of the liver (0.63, sensitivity) than in controls (0.17). Mosaic-like pattern was the most prevalent sign (0.54). Specificity of portal hypertensive gastropathy was 0.83. Portal hypertensive gastropathy was tentatively classified as mild or severe when mosaic-like pattern alone or red marks of any kind were present, respectively; this classification led to a further improvement in reproducibility. CONCLUSIONS: Our results suggest that a sufficient degree of agreement can be achieved in recording portal hypertensive gastropathy. Therefore, the New Italian Endoscopic Club classification should be used to evaluate the natural history of this condition.

Pseudoxanthoma elasticum: a rare cause of gastrointestinal bleeding.

Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder. The main clinical features of this condition are characteristic skin lesions, angioid streaks of the fundus oculi, and occlusive vascular disease. Gastric hemorrhage is a rare complication. A gastroscopic examination was performed on two patients with PXE who presented with upper gastrointestinal tract bleeding. The two patients had submucosal yellowish nodular lesions similar to the xanthoma-like skin lesions seen in the disease. We suggest that a diagnosis of PXE be considered for any patient with gastrointestinal hemorrhage, especially if routine clinical and endoscopic examination fail to reveal the cause, and if raised yellow plaque-like lesions are seen in the stomach by endoscopy.

The natural history of hepatocellular carcinoma.

Prospective studies of patients with cirrhosis who are at risk for developing hepatocellular carcinoma (HCC), have greatly improved our understanding of the natural history of this tumour. Despite many studies, the controversy of whether HCC originates from one or more than one clone of transformed liver cells is still unsettled. The natural history of HCC in many instances is an extension of that of the underlying cirrhosis, although the course of the tumour disease may vary from patient to patient and in different geographical areas. In Oriental and southern European patients with HCC, a longer time may elapse between diagnosis and death, than in African blacks. The information about tumour development in non-cirrhotic liver is scanty, due to the little known risk factors for this type of tumour which has impeded performing prospective cohort studies of high risk patients.

Hepatitis C virus and hepatocellular carcinoma.

Epidemiological, clinical and laboratory data point to a role of hepatitis C virus infection in hepatocellular carcinoma. The connection appears to be indirect and to be mediated by cirrhosis. Thus, geographical differences can be observed, based on the locally prevalent etiological factors for cirrhosis. In the end, prospective studies of hepatitis C virus infected persons will be needed to elucidate the role of this agent in liver cancer.

Hepatocellular carcinoma in Italian patients with cirrhosis.

BACKGROUND AND METHODS: Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months. RESULTS: Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery. CONCLUSIONS: In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors.