Clastogenic factors in the plasma of patients with hepatitis C: their possible role at the origin of hepatocarcinoma.

Clastogenic factors (CF) are endogenous clastogens composed of lipid peroxidation products, cytokines, and abnormal nucleotides of inosine. They are regularly observed after radiation exposure and in chronic inflammatory diseases, where they are supposed to be risk factors for carcinogenesis. In the present study, we evaluate clastogenic activity in the plasma of patients with chronic hepatitis C, HCV-positive liver cirrhosis, and hepatocarcinoma in comparison to liver metastasis. Plasma ultrafiltrates from patients were added to blood cultures of healthy donors (CF test). The chromosomal aberration rates observed in 100 metaphases after 48 hours of cultivation were expressed as adjusted clastogenic scores (ACS). The differences in ACS between the four patient groups and controls were highly significant and represented a 10-fold increase in chromatid-type aberrations. The ACS of patients with cirrhosis and hepatocarcinoma were higher than those of hepatitis patients without these complications, but the differences did not reach statistical significance. Because of cytotoxic effects, the cultures did not grow for 10/17 patients with hepatocarcinoma and were repeated with a reduced volume of ultrafiltrate (0.1 instead of 0.25 mL). The ACS were highest in these 10 patients. When the CF activity of HCV-positive hepatocarcinoma was compared to metastasis because of other malignancies, the differences in ACS were highly significant for the cultures set up with the reduced quantity of ultrafiltrate. The percentage of CF-positive samples was 100% for hepatocarcinoma and 9% for metastasis. The results show that the chromosome-damaging effects of CF increase as the disease progresses to cirrhosis and liver cancer. Formed via the intermediacy of superoxide and generating more superoxide, CF are responsible for an autosustained, long-lived DNA-damaging process, which is documented at the chromosomal level by our technique.

Factors associated with the development of cirrhosis in patients with HCV chronic infection.

BACKGROUND/AIMS: The natural history of chronic hepatitis C virus (HCV) infection still has some details to be established, namely in what concerns progression to hepatic cirrhosis (HC). The study aims to define predictive factors for progression to HC in patients with HCV chronic infection. METHODOLOGY: A cross-sectional study was performed on 129 patients consecutively submitted to liver biopsy. Thirty-six percent (n=46) had HC at histological evaluation. RESULTS: Patients with HC did not show statistically significant differences on gender, viruses genotypes, alcohol consumption or proportion of positivity to markers of previous hepatitis B virus (HBV) infection - anti-HBc/anti-HBs+. Patients with HC seem to have had their infection sporadically (50%) or post-transfusion (35%) -p=0.052, and iv drugs addiction was related to non-HC patients (39%) -p=0.006. Age at infection, time of infection and positivity for anti-HBc/anti-HBs were factors independently related to HC (multivariate analysis). Patients older than 40 years by the time of infection [OR=4.5 (95% CI=1.9-10.8], those with less than 5 years of time of infection [OR=4.2 (95% CI=1.6-10.8)], and patients with previous HBV infection [OR=2.51 (1.00-6.69)] are at higher risk for HC. CONCLUSIONS: We argue that older patients, with a shorter time interval between HCV infection and diagnosis, and namely those with markers for previous HBV infection represent patients with higher risk for progression to hepatic cirrhosis.

Oxidative stress in chronic hepatitis C: a preliminary study on the protective effects of antioxidant flavonoids.

BACKGROUND/AIMS: Oxidative stress is involved in chronic hepatitis C, and efforts have been made to influence the disease process with antioxidants. The present study evaluates the protective effects of a phenol-rich processed grain food with superoxide-scavenging properties (trade name antioxidant biofactor AOB). METHODOLOGY: Thirty patients participated in this placebo-controlled double-blind pilot study. AOB was taken orally by fifteen patients for 3 mo at the recommended daily dose of 3x2 sachets, containing 3 g of powder each. Another fifteen patients received a herbal extract with practically no superoxide scavenging properties as a placebo. Oxidative stress biomarkers, aminotransferase levels and viral load were evaluated immediately before and after treatment. RESULTS: AOB treatment considerably improved the antioxidant defenses. Also ALT and AST decreased in 11 of the 15 patients (-11% to -65%, mean -22%, p<0.05). The effects of placebo were not significant. Viral load remained unchanged. Control biopsies were not done after the short interval of 3 mo. There were no adverse effects. After the 3-mo treatment with AOB or placebo, 16 of the 30 patients received conventional antiviral treatment (pegylated interferon alpha and ribavirin). A sustained response was observed in 5 of 9 AOB pretreated patients six mo after discontinuation of the 12-mo antiviral therapy. The 7 patients pretreated with placebo were all non-responders. CONCLUSIONS: These preliminary results are encouraging to conduct more extensive clinical studies combining antioxidant with antiviral treatment in hepatitis C.

[Natural history and clinical manifestations of chronic hepatitis B virus]. / Historia natural y manifestaciones clínicas de la hepatitis B crónica.

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. In the last few decades, major advances have been achieved that have contributed to greater understanding of the natural history and clinical manifestations of this infection. The fluctuation between viral replication and the host's immune response has implications in the pathogenesis and progression of the hepatic lesion. In immunocompetent adults, most HBV infections resolve spontaneously in contrast with progression to chronic infection in most infants. Patients with chronic hepatitis due to HBV or chronic hepatitis B can present at four phases: 1) the immune tolerance phase, 2) HBeAg-positive chronic hepatitis B, 3) inactive HBsAg carrier state, and 4) HBeAg-negative chronic hepatitis. HBeAg-positive or -negative chronic hepatitis can progress to cirrhosis, liver failure and hepatocellular carcinoma. Progression to these complications is more frequent in HBeAg-negative forms, associated with mutations that affect the pre-core region and maintain active viral replication. Risk factors are HBV-DNA positive serum levels, an increase in serum transaminase levels and some genotypes. These factors highlight the need to evaluate and monitor all HBV carriers to identify those who could benefit from early antiviral treatment, thus avoiding progression to more advanced forms of liver disease. These measures could improve prevention and treatment of hepatitis B.

A ten-year prospective study on gallbladder stone recurrence after successful extracorporeal shock-wave lithotripsy.

OBJECTIVE: The risk of recurrence has limited the acceptability of conservative therapies of gallbladder stones. The aim of the present study was to determine the long-term rate of stone recurrence and its risk factors after successful extracorporeal shock-wave lithotripsy (ESWL). MATERIAL AND METHODS: The study comprised a prospective ultrasound follow-up at yearly intervals or whenever biliary pain was reported. A total of 192 consecutive patients (primary single stones, n=159; primary 2 or 3 stones, n=33) were followed for up to 11.2 years after becoming stone-free and after termination of adjuvant treatment with ursodeoxycholic acid (UDCA). RESULTS: Eighty-four patients developed recurrent stones after a median of 2.6 years (maximum?=?8.8 years). The 108 patients without recurrence were followed for a median of 6.7 years (maximum=11.2 years). By actuarial analysis, the cumulative recurrence rates for these 192 stone-free patients were 27%+/-3%, 41%+/-4% and 54%+/-4% (observed +/-SE) at 3, 5 and 10 years, respectively. Cox's regression analysis was used to identify the presence of slight calcification in the primary stone(s) as a protective feature against recurrence (p=0.03). CONCLUSIONS: 1) The risk of recurrence continues to increase over time, and although it rises less steeply after 5 years, it does not reach a plateau until at least 10 years. 2) Having had slightly calcified stone(s) seems to be associated with a reduced risk of recurrence and might signal a "burnt out" lithogenic process. 3) The long-term results are unsatisfactory and ESWL of gallbladder stones should be offered only in special cases.