Surveillance for hepatocellular cancer with ultrasonography vs. computed tomography -- a randomised study.

BACKGROUND: Guidelines recommend screening for hepatocellular cancer (HCC) with ultrasonography. The performance of ultrasonography varies widely. Computed tomography (CT) is less operator dependent. AIM: To compare the performance and cost of twice-a-year ultrasonography to once-a-year triple-phase-contrast CT for HCC screening in veterans. We hypothesised that CT detects smaller HCCs at lower overall cost. METHOD: One hundred and sixty-three subjects with compensated cirrhosis were randomised to biannual ultrasonography or yearly CT. Twice-a-year alpha-feto protein testing was performed in all patients. Contingency table analysis using chi-squared tests was used to determine differences in sensitivity and specificity of screening arms, survival analysis with Kaplan-Meier method to determine cumulative cancer rates. Multivariate logistic regression models were used to examine predictive factors. RESULTS: Hepatocellular cancer incidence rate was 6.6% per year. Nine HCCs were detected by ultrasonography and eight by CT. Sensitivity and specificity were 71.4% and 97.5%, respectively, for ultrasonography vs. 66.7% and 94.4%, respectively, for CT. Although 58.8% of screen-detected HCC were early stage (Barcelona Clinic Liver Cancer stage A), only 23.5% received potentially curative treatment despite all treatment options being available. HCC-related and overall mortality were 70.5% and 82.3%, respectively, in patients with screen-detected tumour. Overall costs were less for biannual ultrasonography than annual CT. CONCLUSIONS: Biannual ultrasonography was marginally more sensitive and less costly for detection of early HCC compared with annual CT. Despite early detection, HCC-related mortality was high. These data support the use of biannual ultrasonography for HCC surveillance in a US patient population (NCT01350167).

Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population.

OBJECTIVE: The prevalence of psychiatric problems and substance abuse is high in the veteran population with hepatitis C. The purpose of this study was to retrospectively analyze the effect of preexisting psychiatric conditions in veteran patients undergoing treatment with interferon a-2b (IFN-alpha) with respect to adverse events, compliance, and treatment response. METHODS: Thirty-three veterans with chronic hepatitis C were treated with IFN-alpha (5 million units three times weekly) for 6 months, followed by a tapering dose for an additional 6 months. All patients fulfilled standard criteria for treatment eligibility. Psychiatric diagnoses, adverse events, and virological and biochemical responses to therapy were determined. RESULTS: Nineteen of 33 (58%) patients with hepatitis C had documented psychiatric conditions before starting IFN-alpha therapy. Of the patients with preexisting psychiatric diagnoses, 13/19 (68%) developed major adverse events requiring intervention or discontinuation of therapy. In contrast, 4/14 (29%) patients without psychiatric diagnoses developed major adverse events (p = 0.024) In the psychiatric group, 6/19 (32%) developed major neuropsychiatric side effects compared with 2/14 patients (14%) in the nonpsychiatric group (p = 0.25). Patients with and without psychiatric diagnoses had equivalent biochemical and virological responses to therapy. Overall, only 2/33 (6%) patients had a sustained virological response. CONCLUSIONS: Veterans with chronic hepatitis C and psychiatric diagnoses experienced a significantly greater number of major adverse events during treatment with IFN-alpha. Veteran patients with hepatitis C should be carefully screened for psychiatric conditions and may require more intensive monitoring during IFN-alpha therapy.

Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: A review.

OBJECTIVE: Neuropsychiatric symptoms are commonly associated with chronic hepatitis C virus infection, its sequelae, and its treatment. In particular, interferon, a primary component of treatment for chronic hepatitis C, has been strongly associated with depressive symptoms. This review summarizes current knowledge about the etiology, course, and treatment of neuropsychiatric problems associated with hepatitis C and interferon alpha (IFN-alpha) treatment. METHOD: Studies were identified by computerized searches, and further references were obtained from bibliographies of the reviewed articles. RESULTS: Chronic infection with the hepatitis C virus is a common and growing problem, often affecting persons with psychiatric and substance use problems. Although changes in cognition, mood, and personality have been described in association with hepatitis C and with IFN-alpha treatment, there has been little systematic study of these changes. CONCLUSIONS: Psychiatrists should become familiar with the clinical spectrum associated with hepatitis C virus infection as well as the neuropsychiatric symptoms related to hepatitis C and IFN-alpha treatment. More studies are necessary to define the neuropsychiatric syndromes associated with this population and to find possible effective treatments. Furthermore, research is needed so that patients with psychiatric problems are not excluded from effective treatments for this growing medical problem.

Genomic organization of lignin peroxidase genes of Phanerochaete chrysosporium.

Three lignin peroxidase (LiP) genes from the basidiomycete Phanerochaete chrysosporium were cloned on a single 30 kb cosmid insert. One gene, GLG5, is the genomic equivalent of a previously reported cDNA clone, CLG5. The other two LiP genes are transcriptionally convergent and map to a position approximately 15 kb downstream of GLG5. The translational stop codons of these genes are separated by 1.3 kb. Analysis of homokaryons established allelic relationships to previously described LiP clones. Using clamped homogeneous electrical field electrophoresis (CHEF), seven chromosomal bands were resolved from P. chrysosporium genomic DNA. On CHEF gel Southern blots, the LiP gene family was localized to a single, dimorphic chromosome.