Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.

BACKGROUND: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients.

BACKGROUND: It is not known whether putative etiologic factors and clinical and pathological features of hepatocellular carcinoma (HCC) differ between young adult and older white patients. METHODS: We examined the characteristics of 498 consecutive patients with HCC age < 50 years (Group 1: 54 patients) and age > or = 50 (Group 2: 444 patients), an age beyond which the tumor occurrence rate briskly increases. RESULTS: Demographic characteristics, alcohol and coffee intake, and cigarette smoking did not differ between the two groups. Group 1 had a greater prevalence of the hepatitis B surface antigen (HBsAg) carriers (P = 0.006), while the prevalence of either past hepatitis B virus infection (P = 0.008) or antivirus C antibodies (P = 0.016) was higher in Group 2. The lack of both hepatitis B and C virus serologic markers was more common in Group 1 (P = 0.018). In these patients, HCC was less frequently superimposed on cirrhosis (P = 0.002) and was more advanced at the time of diagnosis. In fact, despite a better histologic differentiation grade (P = 0.019), monofocal (solitary and massive) tumors were larger (P = 0.012), small lesions (< or = 5 cm) less frequent (P = 0.028), and either diffuse (P < 0.001) or massive (P = 0.011) types more common. An elevation of serum alpha-fetoprotein was less frequent in group 1 (P = 0.016), but this difference disappeared when the "diagnostic" cut-off of 400 ng/mL was considered. Albeit the prevalence of presenting symptoms did not significantly differ between the two groups, the clinical stage was more advanced in young patients (P = 0.004). The 9-year cumulative rate of survival was similar in the 2 groups. CONCLUSIONS: An early exposure to the virus and/or an accelerated hepatocarcinogenesis in HBsAg carriers can be inferred. Moreover, in the period of life at low risk for hepatoma: (1) the impact of nonalcoholic chemical carcinogenesis seems to be greater; (2) the tumor occurrence is less dependent on cirrhosis development; (3) although histologically better differentiated, the neoplasm is more advanced at the time of diagnosis; and (4) the long term survival is similar to that of the patients age 50 years or older.

High plasma levels of atrial natriuretic peptide in preascitic cirrhosis: indirect evidence of reduced natriuretic effectiveness of the peptide.

Controversial results come from spot measurements of plasma atrial natriuretic peptide (ANP) in compensated cirrhotic patients. Moreover, either blunted or exaggerated natriuresis has been described after maneuvers increasing plasma ANP. This does not make it possible to delineate the ANP effectiveness. Plasma ANP, renin activity (PRA) and aldosterone and hematocrit were serially measured (7 AM, 9 AM, 6 PM, and 11 PM) in nine preascitic cirrhotic outpatients and in nine healthy subjects on normal sodium diet (150 mmol/day) and carrying on their usual activities (mobile from 7 AM to 10 PM). Daily natriuresis was monitored the day before and during the study. In both groups, ANP peaked at the end of the recumbence period (7 AM) and declined on the assumption of the upright position, so that both ANP values of the standing period were significantly lower than the mean daily level. These fluctuations were reciprocal to PRA and hematocrit changes. Patients showed steadily elevated plasma ANP and reduced PRA (ANP mean daily level: 33.3 +/- 3.8 vs. 15.5 +/- 3.2 pg/mL, P = .004; PRA: 0.76 +/- 0.23 vs. 1.66 +/- 0.21 ng/mL/hr, P = .003). Aldosterone fluctuations and mean daily level were similar in the two groups (mean daily level: 122 +/- 11 vs. 119 +/- 9 pg/mL). Natriuresis was well adapted to the sodium intake and similar in healthy subjects (day 1: 152 +/- 11 mmol; day 2: 138 +/- 12.5 mmol) and patients (143 +/- 15 mmol; 148 +/- 29 mmol). Preascitic cirrhotic patients on a normal salt intake and carrying on their usual activities develop a new steady state requiring increased ANP levels to maintain a sodium balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Etiologic factors and clinical presentation of hepatocellular carcinoma. Differences between cirrhotic and noncirrhotic Italian patients.

BACKGROUND: It is not known whether the prevalence of hepatocarcinogenic factors differs between cirrhotic and noncirrhotic patients with hepatocellular carcinoma (HCC) or whether the clinical presentation of HCC in these two groups differs. METHODS: The prevalence of the putative etiologic factors of HCC and its clinical presentation in 373 patients with cirrhosis and 102 without cirrhosis seen from 1981 to 1992 were evaluated. RESULTS: Hepatitis C virus infection (76 vs. 48%, P = 0.003) and both current (22.5 vs. 10%, P = 0.007) and past (50.5 vs. 34.5%, P = 0.045) hepatitis B virus infections were more common in cirrhotic than in noncirrhotic patients with HCC. The absence of exposure to both viruses was much less frequent in the former (7 vs. 40%, P < 0.001). Heavy alcohol intake prevailed in patients with cirrhosis (30 vs. 16.5%, P = 0.01). Alpha-fetoprotein elevation was more common in cirrhotic patients (63% vs. 31%, P < 0.001); however, the prevalence of diagnostic (> 400 ng/ml) levels did not differ significantly (24 vs. 17%) between the two groups. Extrahepatic extension of HCC was more common in noncirrhotic patients (20.5 vs. 6.5%, P < 0.001) and its independent predictors were poor cancer differentiation and absence of cirrhosis. "Asymptomatic" cancers were more frequently encountered with cirrhosis. Abdominal pain was the most common presenting symptom in both groups. Signs of hepatic decompensation prevailed in cirrhotic patients, whereas a "toxic syndrome" dominated the clinical picture of the noncirrhotic patients. CONCLUSIONS: Hepatitis viruses are associated more with carcinogenesis of the cirrhotic than of the noncirrhotic liver. Alpha-fetoprotein is not a sensitive neoplastic marker, particularly in noncirrhotic patients. In the latter, HCC appears more advanced at diagnosis and symptoms of neoplastic toxicity are prominent.

Effects of prolonged ingestion of graded doses of licorice by healthy volunteers.

Licorice can induce a hypermineralocorticoid syndrome. Current literature usually refers to the effects of sweets containing glycyrrhizin, but little is known about the consequences of a prolonged intake of "pure licorice". We administered graded daily doses of dried, aqueous extract of licorice root, containing 108, 217, 380 and 814 mg of glycyrrhizin, to 4 groups of 6 healthy volunteers of both sexes for 4 weeks. No significant effects occurred in groups 1 and 2. After 2 weeks, side effects leading to withdrawal from the protocol occurred in a female in group 3 (headache), a male with a family history of hypertension in group 4 (arterial hypertension), and a female also taking oral contraceptives in group 4 (hypertension, hypokalaemia and peripheral edema). In group 4, transient reduction in kalaemia and increase in body weight were found after 1 and 2 weeks, respectively. A depression of plasma renin activity occurred in groups 3 and 4. In healthy subjects, only the highest doses of licorice led to untoward effects. These were favoured by subclinical disease or oral contraceptives, and were less common and pronounced than what has been reported after the intake of glycyrrhizin taken as such or as a flavouring agent in confectionery products.

Gross pathologic types of hepatocellular carcinoma in Italian patients. Relationship with demographic, environmental, and clinical factors.

BACKGROUND: The prevalence of the different hepatocellular carcinoma (HCC) macroscopic types, and the association between these types and age, gender, blood group, alcohol and coffee intake, smoking habit, hepatitis virus markers, underlying cirrhosis, and cancer histologic type were retrospectively assessed in 416 unselected patients (321 with cirrhosis). METHODS: The gross pathologic types of HCC were assessed by ultrasonography combined, in most cases, with computed tomography and angiography. RESULTS: Solitary HCC was the most common cancer type (54.8%), followed by the multinodular (31%), diffuse (7.7%), and massive (6.5%) types. Cirrhosis and blood group other than O were independent risk factors for multinodular HCC (relative risk [RR] 1.6, P < 0.05; and RR 1.7, P < 0.005, respectively); the absence of cirrhosis and a heavy smoking habit were risk factors for the massive type (RR 4.9, P < 0.001; and RR 3.3, P < 0.01, respectively); and blood group O for the solitary type (RR 1.4, P < 0.001). The prevalence of highly undifferentiated cells increased as the tumor size did, so that grade IV cell atypia was associated with massive size of the carcinoma (P < 0.05). In cirrhotic patients, advanced liver dysfunction was associated with diffuse HCC (P < 0.05). As far as solitary HCC is concerned, the tumor size was greater in noncirrhotic than in cirrhotic patients (7 +/- 0.4 cm versus 4.8 +/- 0.15, P < 0.001). CONCLUSIONS: In Italian patients, HCC presents most frequently as a solitary nodule. The presence or absence of cirrhosis, blood group, and smoking habit can influence the likelihood of developing certain HCC shapes. The probability of harboring highly undifferentiated cells increases as the cancer increases in size. In cirrhosis, advanced liver dysfunction may predispose to diffuse HCC.