Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients.

BACKGROUND: Morphological, haemodynamic and clinical stages of cirrhosis have been proposed, although no definite staging system is yet accepted for clinical practice. AIM: To investigate whether clinical complications of cirrhosis may define different prognostic disease stages. METHODS: Analysis of the database from a prospective inception cohort of 494 patients. Decompensation was defined by ascites, bleeding, jaundice or encephalopathy. Explored potential prognostic stages: 1, compensated cirrhosis without oesophago-gastric varices; 2, compensated cirrhosis with varices; 3, bleeding without other complications; 4, first nonbleeding decompensation; 5, any second decompensating event. Patient flow across stages was assessed by a competing risks analysis. RESULTS: Major patient characteristics were: 199 females, 295 males, 404 HCV+, 377 compensated, 117 decompensated cirrhosis. The mean follow-up was 145 ± 109 months without dropouts. Major events: 380 deaths, 326 oesophago-gastric varices, 283 ascites, 158 bleeding, 146 encephalopathy, 113 jaundice, 126 hepatocellular carcinoma and 19 liver transplantation. Patients entering each prognostic stage along the disease course were: 202, stage 1; 216, stage 2; 75 stage 3; 206 stage 4; 213 stage 5. Five-year transition rate towards a different stage, for stages 1-4 was 34.5%, 42%, 65% and 78%, respectively (P < 0.0001); 5-year mortality for stages 1-5 was 1.5%, 10%, 20%, 30% and 88% respectively (P < 0.0001). An exploratory analysis showed that this patient stratification may configure a prognostic system independent of the Child-Pugh score, Model for End Stage Liver Disease and comorbidity. CONCLUSION: The development of oesophago-gastric varices and decompensating events in cirrhosis identify five prognostic stages with significantly increasing mortality risks.

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection: a validated prognostic model.

OBJECTIVE: Percutaneous ethanol injection may prolong the survival of patients with small hepatocellular carcinoma associated with cirrhosis. The aim was to identify prognostic factors of survival and of local recurrence, as well as separate new lesions. METHODS: We performed Cox regression analysis in 115 consecutive patients with hepatocellular carcinoma (81 Child-Pugh class A, 34 Child-Pugh class B) treated by percutaneous ethanol injection. The validity of the model was tested by comparing predicted and observed survival in 105 independent patients from an external series. RESULTS: Overall survival rates were 89%, 63%, and 43% at 1, 2, and 3 yr, respectively. The 1-, 2-, and 3-yr survival rates were 96%, 78%, and 63%, respectively, for Child-Pugh class A patients and were 73%, 35%, 12%, respectively, for Child-Pugh class B. The albumin level was the only independent variable significantly associated with survival (p < 0.0001). The 3-yr rate of appearance of separate new lesions and local recurrence were 41% and 23%, respectively. The survival predicted by the model agreed with that observed in the independent patients. CONCLUSIONS: Survival of patients with hepatocellular carcinoma treated by percutaneous ethanol injection is related to baseline albumin level. The high rate of recurrence (both local and distant) points out the palliative role of this therapy.

Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study.

BACKGROUND: Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. AIMS: To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. METHODS: Prospective cohort study; prognostic analysis by the Cox proportional hazards model. RESULTS: A total of 218 consecutive cirrhotic patients (37 Child class A, 154 B, 27 C) were enrolled in the study Varices were obliterated in 139 (64%) patients in a mean of 5 (+/-2.6) sessions and recurred in 58/139 (41.7%) within one year. A total of 132 (60%) patients experienced 283 rebleeding episodes and 73 (33%) died. Bleeding from oesophageal ulcers was the most serious complication causing 14% of all rebleeding episodes. Significant prognostic indicators of sclerotherapy outcome were: Child-Pugh class for variceal obliteration; gastric varices and platelet count for recurrence of varices; failure to obliterate varices, variceal size and gastric varices for rebleeding; blood urea nitrogen and failure to obliterate varices for death. Presence of gastric varices was the only prognostic indicator for death in the 79 patients not achieving variceal obliteration. A mean of 10 endoscopies and of 6 hospital admissions were needed per each patient with an estimated cost of US dollars 7154 per patient during the first two years of therapy. CONCLUSIONS: Sclerotherapy is a very demanding and costly treatment, and is associated with frequent and serious side-effects. The probability of treatment failure is significantly higher in Child C patients with gastric varices. Alternative treatments should be considered for these patients.

Treatment of small hepatocellular carcinoma associated with cirrhosis by percutaneous ethanol injection. A trial with a comparison group.

BACKGROUND: Ethanol injection has been reported to be effective in the treatment of hepatocellular carcinoma, but no controlled randomized trials have been performed. We therefore performed a trial comparing ethanol injection with an untreated, matched historical comparison group in the treatment of hepatocellular carcinoma. METHODS: From 1992 to 1993, 35 patients (14 Child's A and 21 Child's B cirrhosis) with small (< 4 cm) hepatocellular carcinoma associated with cirrhosis were treated by ethanol injection. Each patient was matched with an untreated case (followed up during the period 1984-89) for variables known to have independent prognostic value (age, Child's classification, number of lesions, alpha-fetoprotein, and modality of diagnosis). RESULTS: The 1-, 2-, and 3-year survival rates of ethanol-treated patients were 86% (95% confidence interval (CI), 69-94), 53% (95% CI, 34-68), and 33% (95% CI, 15-52), whereas the survival rates of the comparison group were 75% (95% CI, 56-85), 26% (95% CI, 13-41), and 14% (95% CI, 5-27) (P = 0.01). The 1-, 2-, and 3-year survival rates of Child's A were 100%. 87% (95% CI, 30-97), 71% (95 CI, 33-90), 71% (95% CI, 33-90) in the ethanol-treated patients and 92 (95% CI, 59-99), 43% (95% CI, 23-73), and 21% (95% CI, 23-72) in untreated patients. The 1-, 2-, and 3-year survival of Child's B patients were 76% (95% CI, 59-97), 32% (95% CI, 13-53), and 9% (95% CI, 0.8-33) in the treated group and 61% (95% CI, 40-83), 14% (95% CI, 3-32), and 9% (95% CI, 1-26) in the treated group. CONCLUSIONS: These data suggest that ethanol injection prolongs the life of patients with hepatocellular carcinoma associated with Child's A cirrhosis but seems not to influence the survival of Child's B patients.

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.

Ultrasound changes in abdominal echinococcosis treated with albendazole.

Fifty patients with 81 abdominal hydatid cysts were followed with ultrasound during and after treatment with albendazole. In 61 cysts (75%), regressive changes were observed after treatment. Detachment of the membrane and change to a solid pattern in anechoic cysts were observed. Disappearance of septa or change to a solid pattern in anechoic cysts with intracystic septation were also found. There was an increase of hyperechoic structures in cysts with a mixed pattern. Follow-up ultrasound examination showed disappearance of 7 cysts, while anechoic structures reappeared in five cases. In anechoic cysts, regressive changes due to albendazole seem to be permanent, but in cysts with a mixed pattern recurrences are sometimes observed.

Asymptomatic hepatocellular carcinoma in Child's A cirrhosis. A comparison of natural history and surgical treatment.

The present study deals with the natural history of 37 asymptomatic patients with cirrhosis and hepatocellular carcinoma, 25 with 2-9-cm tumors who were not surgically treated (first group) and 12 with tumors smaller than 4 cm who underwent resection (second group). All patients were in Child's A class. Two-year survival (according to life-table analysis by the Kaplan-Meier method) was 50% in the first group and 39% in the second group. This difference was not significant. In the first group no relation was found between survival and initial tumor size or alpha-fetoprotein levels. Ultrasound examinations at 3-mo intervals revealed the following patterns of tumor growth: (a) no significant growth during the follow-up (9 patients); (b) significant growth (tumor size at least doubling) only in the final stage of the disease (11 patients); (c) initial significant growth followed by a period of no increase in size (5 patients). These findings show that in our geographical area (a) 2-yr survival of untreated asymptomatic patients with hepatocellular carcinoma associated with cirrhosis does not differ from that of similar patients undergoing resection and (b) the tumor can exhibit long periods of no growth alternating with periods of exponential growth.

[Evolution of the echographic picture in primary liver tumor associated with cirrhosis]. / Evoluzione del quadro ecografico nel tumore primitivo del fegato associato a cirrosi.

To study the sonographic (US) evolution of hepatocellular carcinoma, 53 tumors in 45 untreated patients were observed regularly with real-time US for a period of 6 to 56 months. At the beginning, 25 tumors were hypoechoic, 18 isoechoic, 4 hyperechoic, and 6 had mixed hypo/hyper echo patterns. At the follow-up, 7 initially hypoechoic tumors had changed to hyperechoic or to mixed echo patterns; 8 hypoechoic tumors had become isoechoic; 9 of the 25 initially hypoechoic neoplastic lesions had maintained the same echo density. Ten of the 15 initially isoechoic tumors had changed to mixed echo patterns, and 5 had remained unchanged. Three initially isoechoic lesions and a hypoechoic one had turned into diffuse patterns; 2 initially hyperechoic neoplastic lesions had remained unchanged; 1 had switched into hypoechoic, and 1 changed to mixed echo pattern; 4 out of 6 tumors with echo pattern had remained unchanged, 1 had become hyperechoic and 1 hypoechoic. The current study has proven various tumors less than or equal to 3 cm phi to be isoechoic, and most tumors greater than 3 cm phi to have mixed hypo/hyper echo patterns. The echogenicity of small hepatocellular carcinomas increases with the tumor growth, and remains unchanged when they do not increase in size.

Early detection of hepatocellular carcinoma associated with cirrhosis by ultrasound and alfafetoprotein: a prospective study.

A prospective surveillance of hepatocellular carcinoma (HCC) associated with cirrhosis, using alfafetoprotein (AFP) and real-time ultrasonography (US) was carried out in 157 patients with histologically proven cirrhosis. During a two-year follow-up, 15 asymptomatic HCCs were identified. HCCs detected by these methods were at a relatively early stage, as most tumors were small (13 out of 15 less than 5 cm). US was more sensitive than AFP in the diagnosis of HCC when values greater than 400 ng/ml were considered. Patients with initial AFP values greater than 20 ng/ml developed HCC within two years more frequently than patients with values less than 20 ng/ml. A combined approach using US and AFP is suggested in our geographical area.

Is the acidity of ascitic fluid a reliable index in making the presumptive diagnosis of spontaneous bacterial peritonitis?

Ascitic fluid pH and arterial-ascitic fluid pH gradient were compared to ascitic fluid polymorphonuclear cell count in 84 patients with cirrhotic ascites and in 12 with malignant ascites to assess their role as diagnostic tests for spontaneous bacterial peritonitis and to clarify the relationship between ascitic fluid pH and lactate. Ascitic fluid pH was significantly lower (pH 7.30) in spontaneous bacterial peritonitis (n = 18) and probable spontaneous bacterial peritonitis (n = 12) than in sterile ascites (pH 7.41; n = 54). Since blood pH levels were not different in the presence of infection, arterial-ascitic fluid pH gradient was significantly higher in spontaneous bacterial peritonitis and probable spontaneous bacterial peritonitis than in sterile ascites (0.12 vs. 0.02). The close correlations between arterial-ascitic pH gradient and lactate (r = 0.77, p less than 0.0001), lactate and bicarbonate gradient (r = 0.64, p = 0.003) and arterial-ascitic pH gradient and pCO2 gradient (r = -0.90, p less than 0.0001) suggest that the low ascitic fluid pH may be due to an increase in lactate and CO2. Patients with Escherichia coli-induced spontaneous bacterial peritonitis had significantly lower ascitic fluid pH and higher lactate than those with spontaneous bacterial peritonitis by other organisms. Values of ascitic fluid pH, lactate and arterial-ascitic fluid pH gradient in malignant ascites were similar to those of spontaneous bacterial peritonitis and probable spontaneous bacterial peritonitis. Cutoff points, selected by receiver operating characteristic curves analysis, of 450 per mm3 for polymorphonuclear cells and of 0.07 for arterial-ascitic fluid pH gradient, allow high positive and negative predictive values for spontaneous bacterial peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)