Hepatitis C Virus Infection in Haemodialysis Patients: “Wolf in Sheep's Clothing”

Background

170 million people are infected with the Hepatitis C virus (HCV) around the world. Approximately 50%-70% patients infected with HCV develop chronic liver disease. Haemodialysis patients constitute an especially important group with high HCV prevalence. Outbreaks of HCV infection in dialysis units have been documented. Detection of anti-HCV antibodies is a convenient and conventional mode of documentation. However, in this group, it has it''s own caveats.

Methods

48 patients who had undergone or were on haemodialysis (HD) and had undergone a minimum of 15 dialysis sittings were studied. HCV infection was documented both by anti-HCV antibody detection and HCV RNA testing. A comparative evaluation of results by both tests was done.

Results

Out of a total of 48 patients, HCV RNA was detected in 38 (79.16%) and anti-HCV antibodies in 13(27.07%). Out of 48 patients 10(20.83%) were negative for both parameters. 22.91% (11/48) of patients were positive for both HCV RNA and anti-HCV antibody. 56.25% (27/48) were HCV RNA positive but anti-HCV antibodies were not detectable in their sera. 2 patients (04.16%) had a positive anti-HCV antibody status despite HCV RNA being negative. In 20.83% (10/48) both parameters were undetectable.

Conclusion

Chronic liver disease (CLD), particularly due to HCV infection, is a major complication amongst haemodialysis (HD) patients. Without reliable assays for antigenemia and the inability of antibody tests to define viremia in all cases, the detection of viral nucleic acid is necessary for diagnosis of active HCV infection.Key Words: Hepatitis C virus, Haemodialysis     

Is surgery getting safer? National trends in operative mortality

BACKGROUND: Although mortality rates for some cardiovascular procedures seem to have declined, it is unclear whether other high-risk procedures are becoming safer over time. STUDY DESIGN: We examined national trends between 1994 and 1999 in operative mortality for 14 high-risk cardiovascular and cancer procedures in the national population of Medicare beneficiaries over age 65. Secular trends were examined using logistic regression adjusting for age, gender, race, socioeconomic status, admission acuity, comorbidities, and hospital volume. RESULTS: Observed mortality rates varied widely across the 14 procedures, from 2% (carotid endarterectomy) to 16% (esophagectomy). Over the 6-year study period, average patient age increased for all procedures, and patients were more likely to undergo operation at high-volume hospitals for some procedures (pancreatic resection, esophagectomy, cystectomy, and pneumonectomy). After accounting for these changes, operative mortality declined significantly for three cardiovascular procedures, as evidenced by adjusted odds ratios (OR) for the 6-year effect on operative mortality (coronary artery bypass graft OR = 0.85, 95% confidence interval [CI] 0.81 to 0.88; carotid endarterectomy OR = 0.86,95% CI 0.80 to 0.93; mitral valve replacement OR = 0.89, 95% CI 0.81 to 0.97). In contrast, operative mortality did not decline for any of the cancer procedures. In fact, adjusted mortality increased for colectomy for colon cancer (OR= 1.13, 95% CI 1.07 to 1.19). CONCLUSIONS: Although risks of some cardiovascular procedures are declining over time, there is no evidence that other types of high-risk surgery are becoming safer. These findings suggest the need for systematic efforts to monitor and improve surgical performance.     

Metabolic activation of methyl-hydroxylated derivatives of 7,12- dimethylbenz[a]anthracene by human liver dehydroepiandrosterone-steroid sulfotransferase

Methyl-hydroxylated metabolites of the potent carcinogen, 7,12- dimethylbenz[a]anthracene (DMBA), namely, 7-hydroxymethyl-12- methylbenz[a]anthracene (7-OH-DMBA), 7-methyl-12- hydroxymethylbenz[a]anthracene (12-OH-DMBA) and 7,12- dihydroxymethylbenz[a]anthracene (7,12-diOH-DMBA), were examined as substrates for sulfotransferase bioactivation in different human tissue cytosols. Hepatic cytosols, which were able to catalyze the 3'- phosphoadenosine 5'-phosphosulfate (PAPS)-dependent DNA binding of 7-OH- DMBA, 12-OH-DMBA and 7,12-diOH-DMBA, were highly sensitive to inhibition by dehydroepiandrosterone (DHEA), a specific substrate for human DHEA-steroid sulfotransferase (IC50 = 5 microM). By comparison, 2,6-dichloro-4-nitrophenol, a potent inhibitor of the thermostable (TS)- phenol and estrogen sulfotransferases, did not have an appreciable inhibitory effect. Neither p-nitrophenol, a high affinity substrate for human TS-phenol and estrogen sulfotransferases, nor dopamine, a specific substrate for the thermolabile (TL)-phenol sulfotransferase, significantly inhibited the DNA binding of 12-OH-DMBA catalyzed by hepatic cytosols. Inter-subject variation (n = 12) of the PAPS- dependent DNA binding of 12-OH- and 7,12-diOH-DMBAs also correlated well with DHEA-sulfotransferase activity (r = 0.90; P < 0.00001 and r = 0.92; P < 0.00001, respectively). This sulfation-dependent metabolic activation was not detected in cytosols from human colon, pancreas, larynx or mammary gland. Both TS- and TL-phenol sulfotransferases were active in human liver and colon but only liver contained DHEA- sulfotransferase activity. These results indicate that the sulfotransferase-mediated activation of the methyl-hydroxylated DMBAs is predominantly catalyzed by DHEA-steroid sulfotransferase in human liver and that TS- and TL-phenol sulfotransferases and estrogen sulfotransferase are not involved in the catalysis.      

Computed tomographic findings in 50 cases of gall bladder carcinoma

Background : A retrospective assessment of contrast enhanced computed tomography (CECT) scan findings in histopathologically proven cases of carcinoma of the gallbladder (GB) was performed to review its role in diagnosis, staging and assessment of surgical resectability.     

Neoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis

BACKGROUND: The effectiveness in improving survival of neoadjuvant chemoradiotherapy (NCRT) in patients undergoing surgery for esophageal carcinoma remains unclear. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, BIOSIS Previews, and other resources were searched from January 1966 through January 2003. Randomized trials were selected on the basis of study design (NCRT followed by surgery vs surgery alone). Of 21 potential studies identified by abstract review, 6 (29%) met the inclusion criteria. RESULTS: Across 6 studies, a total of 374 patients underwent NCRT followed by surgery and 364 underwent surgery alone. In 5 of the 6 studies in our meta-analysis, there was a small, non-statistically significant trend toward improved survival with NCRT. Only 1 study demonstrated a statistically significant benefit to NCRT. In our summary measure for all 6 studies, we found a small, non-statistically significant trend toward improved long-term survival in the NCRT followed by surgery group (relative risk of death in the NCRT group [RR], 0.86; 95% confidence interval [CI], 0.74 to 1.01; P = .07). CONCLUSIONS: NCRT followed by surgery is associated with a small, non-statistically significant improvement in overall survival. Whether this benefit is sufficient to warrant the considerable expense and risks associated with NCRT should be the subject of future larger randomized trials.