Associations between supplemental or dietary intake of vitamin C and severity of lower urinary tract symptoms.

OBJECTIVE: To examine the association between long-term dietary vitamin C intake and recent use of vitamin C supplements with the progression and severity of lower urinary tract symptoms (LUTS). PARTICIPANTS AND METHODS: Baseline and 5-year follow-up interviews were completed by 2825 black, Hispanic or white men and women aged 30-79 years in the Boston Area Community Health survey. Dietary and supplemental vitamin C intake was assessed using a validated food frequency questionnaire. LUTS were assessed using the validated American Urological Association Symptom Index. Multivariable models were used to test the associations between baseline vitamin C and progression of LUTS over the follow-up period, and between recent vitamin C intake and LUTS severity. RESULTS: In multivariable models, baseline dietary vitamin C was associated with lower odds of progression of daytime storage symptoms in men (e.g. quartile 4 vs 1, odds ratio [OR] = 0.63, 95% confidence interval [CI]: 0.41-0.97), or urgency symptoms in women (P trend = 0.02). Recent vitamin C intake at follow-up was also associated with better symptom scores among men. In contrast, among women, vitamin C supplement intake was associated with worse symptom scores, particularly daytime storage problems (500 mg/day vs none, OR = 1.66, 95% CI: 1.18-2.35, P trend = 0.01). Recent dietary vitamin C was not associated with LUTS in women. CONCLUSION: Vitamin C intake from foods and beverages was inversely associated with progression of daytime urinary storage symptoms in men or urgency symptoms in women at 5-year follow-up, therefore, the present results do not support a widespread avoidance for patients with LUTS of foods and beverages naturally rich in vitamin C. Supplemental vitamin C use above recommended daily intake levels was associated with higher odds of daytime urinary storage symptoms in women, and this finding is worthy of further attention and confirmation in future clinical trials.

HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma.

Hepatitis C virus (HCV) is a major cause of hepatitis and hepatocellular carcinoma (HCC) world-wide. Most HCV patients have relatively stable disease, but approximately 25% have progressive disease that often terminates in liver failure or HCC. HCV is highly variable genetically, with seven genotypes and multiple subtypes per genotype. This variation affects HCV's sensitivity to antiviral therapy and has been implicated to contribute to differences in disease. We sequenced the complete viral coding capacity for 107 HCV genotype 1 isolates to determine whether genetic variation between independent HCV isolates is associated with the rate of disease progression or development of HCC. Consensus sequences were determined by sequencing RT-PCR products from serum or plasma. Positions of amino acid conservation, amino acid diversity patterns, selection pressures, and genome-wide patterns of amino acid covariance were assessed in context of the clinical phenotypes. A few positions were found where the amino acid distributions or degree of positive selection differed between in the HCC and cirrhotic sequences. All other assessments of viral genetic variation and HCC failed to yield significant associations. Sequences from patients with slow disease progression were under a greater degree of positive selection than sequences from rapid progressors, but all other analyses comparing HCV from rapid and slow disease progressors were statistically insignificant. The failure to observe distinct sequence differences associated with disease progression or HCC employing methods that previously revealed strong associations with the outcome of interferon α-based therapy implies that variable ability of HCV to modulate interferon responses is not a dominant cause for differential pathology among HCV patients. This lack of significant associations also implies that host and/or environmental factors are the major causes of differential disease presentation in HCV patients.

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial.

BACKGROUND: The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. METHODS: The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. RESULTS: A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. CONCLUSIONS: Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. TRIAL REGISTRATION: The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164).

Intake of caffeinated, carbonated, or citrus beverage types and development of lower urinary tract symptoms in men and women.

Evidence to substantiate recommendations for restriction of caffeinated or acidic beverages as self-management for lower urinary tract symptoms (LUTS) is limited. We examined longitudinal and acute associations between beverage intake and LUTS in the Boston Area Community Health (BACH) cohort (n = 4,144) between 2002 and 2010. Multivariable models tested associations between baseline intakes and progression of LUTS at 5-year follow-up, between follow-up intakes and International Prostate Symptom Scores at follow-up, and between 5-year intake changes and LUTS progression. Greater coffee or total caffeine intake at baseline increased the odds of LUTS progression in men (coffee: >2 cups/day vs. none, odds ratio = 2.09, 95% confidence interval: 1.29, 3.40, P-trend = 0.01; caffeine: P-trend < 0.001), particularly storage symptoms. Women who increased coffee intake by at least 2 servings/day during follow-up (compared with categories of decreased or unchanged intakes) had 64% higher odds of progression of urgency (P = 0.003). Women with recently increased soda intake, particularly caffeinated diet soda, had higher symptom scores, urgency, and LUTS progression. Citrus juice intake was associated with 50% lower odds of LUTS progression in men (P = 0.02). Findings support recommendations to limit caffeinated beverage intake for LUTS, and in men, they suggest benefits of citrus juice consumption. Further clinical research is warranted, particularly of the precise role of sodas containing artificial sweeteners in bladder sensations and urological function.

Patient satisfaction after midurethral sling surgery for stress urinary incontinence.

OBJECTIVE: To identify factors that may contribute to patient satisfaction with outcome in women who received retropubic and transobturator midurethral slings. METHODS: Satisfaction was assessed 12 months postsurgery as a planned analysis in 597 participants from a multicenter randomized trial comparing retropubic with transobturator midurethral slings using the Incontinence Surgery Satisfaction Questionnaire. Significantly related variables associated with satisfaction in univariable analyses were entered into multivariable logistic regression models to test their independent association with satisfaction. RESULTS: One year after surgery, 264 (88.6%) in the retropubic group and 263 (88.0%) in the transobturator group completed satisfaction questionnaires. Both treatment groups demonstrated a high level of satisfaction with respect to urine leakage (retropubic 85.9% compared with transobturator 90.0%; P=.52), urgency to urinate, frequency of urination, capability of physical activity, social activity, ability to engage in sexual activity, and from an emotional standpoint. Baseline characteristics associated with reduced satisfaction were higher Medical, Epidemiologic, and Social Aspects of Aging Questionnaire urgency subscale scores, detrusor overactivity, and diabetes mellitus. The severity of both objective (frequency of incontinence episodes, pad test weight) and subjective (Incontinence Impact Questionnaire and Urogenital Distress Inventory score) measures of incontinence at baseline and the patients' perceptions of preoperative severity of incontinence and expectations of achieving postoperative cure or improvement were not statistically different between satisfied and unsatisfied patients. In the final multivariable model, satisfaction was associated with overall treatment success (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.29-5.13], greater reduction in Urogenital Distress Inventory (OR 0.97, 95% CI 0.96-0.98) and Incontinence Impact Questionnaire scores (OR 0.99, 95% CI 0.98-0.99), and fewer complications (OR 0.55, 95% CI 0.30-0.99). CONCLUSION: The high level of satisfaction seen after midurethral sling procedures is associated with greater objective and patient-perceived improvement of stress incontinence and fewer complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00325039. LEVEL OF EVIDENCE: II.

Contributors to self-reported health in a racially and ethnically diverse population: focus on Hispanics.

PURPOSE: To understand if Hispanics report health differently than other racial and ethnic groups after controlling for demographics and risk factors for poor health. METHODS: The sample (N = 5502) included 3201 women, 1767 black, 1859 white, and 1876 Hispanic subjects from the Boston Area Community Health Survey, a population-based survey of English- and Spanish-speaking residents of Boston, Massachusetts, United States, aged 30-79 years in 2002-2005. Multiple logistic regression models were used to examine the association between race/ethnicity (including interview language for Hispanics) and fair/poor self-reported health (F/P SRH) adjusting for gender, age, socioeconomic status, depression, nativity, and comorbidities. RESULTS: Compared with whites, Hispanics interviewed in Spanish were seven times as likely to report F/P SRH (odds ratio, 7.7; 95% confidence interval, 4.9-12.2) after adjusting for potential confounders and those interviewed in English were twice as likely. In analyses stratified by depression and nativity, we observed stronger associations with Hispanic ethnicity in immigrants and nondepressed individuals interviewed in Spanish. CONCLUSIONS: Increased odds of F/P SRH persisted in the Hispanic group even when accounting for interview language and controlling for socioeconomic status, age, depression, and nativity, with interview language mitigating the association. These findings have methodological implications for epidemiologists using SRH across diverse populations.

Characteristics of persons with overactive bladder of presumed neurologic origin: results from the Boston Area Community Health (BACH) survey.

AIMS: To compare the descriptive epidemiology of overactive bladder (OAB) of presumed neurologic origin (NOAB) to OAB of non-neurologic origin (N-NOAB). METHODS: Five thousand five hundred three community-dwelling persons aged 30-79 were interviewed regarding urologic symptoms (2002-2005). NOAB was defined as symptoms of urgency and/or urgency incontinence among those with a self-reported history of healthcare provider diagnosed stroke (N = 98), multiple sclerosis (N = 21), or Parkinson's disease (N = 7). N-NOAB was defined identically but occurring among those not reporting neurologic disease (ND). Prevalence estimates were weighted to reflect sampling design; chi-square, Fisher's exact, or t-tests were used to test differences. Urologic symptom interference was assessed using the Epstein scale, while the impact of urinary incontinence (UI) on health-related quality-of-life (HRQOL) was measured using a modification of the Incontinence Impact Questionnaire-7. RESULTS: Forty-five (31.0%) of 125 persons with ND and 994 (16.7%) of 5378 persons without ND reported OAB symptoms. The overall prevalence of NOAB and N-NOAB was 0.6% and 16.4%, respectively. Persons with NOAB had higher (worse) mean American Urologic Association Symptom Index scores (13.0 vs. 10.0, P = 0.09) compared to those with N-NOAB, and were significantly more likely to have diabetes, high blood pressure, cardiac disease, and fair/poor self-reported health (all P < 0.05). Mean symptom interference and UI HRQOL scores were significantly higher (worse) in the NOAB group compared to persons with N-NOAB (all P < 0.05). CONCLUSIONS: Persons with NOAB appeared to have a greater burden of urologic illness with respect to symptom interference and HRQOL compared to persons with N-NOAB.

Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial.

UNLABELLED: Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (k(elim)), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse (P = 0.0017 to P < 0.0001) and spleen volumes were larger (P < 0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as "low" and "high risk" for clinical outcome yielded hazard ratios ranging from 2.21 (95% confidence interval [CI]: 1.29-3.78) for GEC to 6.52 (95% CI: 3.63-11.71) for CA clearance after oral administration (Cl(oral)). QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with high-risk results for CA Cl(oral) or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with "low risk" QLFTs experienced a clinical outcome. CONCLUSION: QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance the noninvasive monitoring, counseling, and management of patients with chronic HCV.

Predicting cirrhosis and clinical outcomes in patients with advanced chronic hepatitis C with a panel of genetic markers (CRS7).

OBJECTIVES: Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC. METHODS: A total of 938 patients (677 Caucasians, 165 African-Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone. RESULTS: Twenty-nine percent (142/493) developed an increase in fibrosis score by greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one or more biopsies, 35% developed at least one clinical outcome, and 13% developed HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04) with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and clinical outcomes were increased in patients with higher CRS7 scores, but were not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A single nucleotide polymorphism in AZIN1 was significantly associated with fibrosis progression. CONCLUSION: CRS7 was validated as a predictor of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of clinical outcome.

Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C.

BACKGROUND & AIMS: High-level coffee consumption has been associated with reduced progression of pre-existing liver diseases and lower risk of hepatocellular carcinoma. However, its relationship with therapy for hepatitis C virus infection has not been evaluated. METHODS: Patients (n=885) from the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial recorded coffee intake before retreatment with peginterferon α-2a (180 µg/wk) and ribavirin (1000-1200 mg/day). We assessed patients for early virologic response (2 log10 reduction in level of hepatitis C virus RNA at week 12; n=466), and undetectable hepatitis C virus RNA at weeks 20 (n=320), 48 (end of treatment, n=284), and 72 (sustained virologic response; n=157). RESULTS: Median log10 drop from baseline to week 20 was 2.0 (interquartile range [IQR], 0.6-3.9) among nondrinkers and 4.0 (IQR, 2.1-4.7) among patients that drank 3 or more cups/day of coffee (P trend<.0001). After adjustment for age, race/ethnicity, sex, alcohol, cirrhosis, ratio of aspartate aminotransferase to alanine aminotransferase, the IL28B polymorphism rs12979860, dose reduction of peginterferon, and other covariates, odds ratios for drinking 3 or more cups/day vs nondrinking were 2.0 (95% confidence interval [CI]: 1.1-3.6; P trend=.004) for early virologic response, 2.1 (95% CI: 1.1-3.9; P trend=.005) for week 20 virologic response, 2.4 (95% CI: 1.3-4.6; P trend=.001) for end of treatment, and 1.8 (95% CI: 0.8-3.9; P trend=.034) for sustained virologic response. CONCLUSIONS: High-level consumption of coffee (more than 3 cups per day) is an independent predictor of improved virologic response to peginterferon plus ribavirin in patients with hepatitis C.

Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial.

BACKGROUND & AIMS: Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis who were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. METHODS: Standard case report forms from 2740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, together with information from questionnaires completed by investigators about details of biopsy techniques used at each hospital. RESULTS: There were 29 serious adverse events (1.1%); the most common was bleeding (16 cases; 0.6%). There were no biopsy-related deaths. The bleeding rate was higher among patients with platelet counts of 60,000/mm(3) or less and among those with an international normalized ratio of 1.3 or greater, although none of the patients with an international normalized ratio greater than 1.5 bled. Excluding subjects with a platelet count of 60,000/mm(3) or less would have reduced the bleeding rate by 25% (4 of 16), eliminating only 2.8% (77 of 2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under ultrasound guidance did not influence the frequencies of adverse events. CONCLUSIONS: Approximately 0.5% of persons with hepatitis C and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in patients with platelet counts of 60,000/mm(3) or less.

Predicting clinical and histologic outcomes based on standard laboratory tests in advanced chronic hepatitis C.

BACKGROUND & AIMS: Predictors of clinical outcomes and histologic progression among patients with chronic hepatitis C and advanced fibrosis are poorly defined. We developed statistical models to predict clinical and histologic outcomes in such patients. METHODS: Baseline demographic, clinical, and histologic data from Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial participants were subjected to multivariate analyses to determine their ability to predict clinical outcomes (ascites, spontaneous bacterial peritonitis, Child-Turcotte-Pugh score >or=7 on 2 consecutive visits, variceal bleeding, hepatic encephalopathy, and liver-related death) and histologic outcome (>or=2-point increase in Ishak fibrosis stage) during the 3.5 years of the trial. RESULTS: Of 1050 randomized patients, 135 had 1 or more clinical outcomes a median of 23 (range, 1-45) months after randomization. Factors associated with a clinical outcome in multivariate analyses were higher aspartate aminotransferase/alanine aminotransferase ratio, lower albumin, lower platelet count, higher total bilirubin, and more advanced Ishak fibrosis score (P < .0001). The cumulative 3.5-year incidence of a clinical outcome was 2% in the lowest and 65% in the highest risk group. Of 547 patients without cirrhosis at baseline and at least 1 follow-up biopsy, 152 had a histologic outcome. Independent variables associated with a histologic outcome were higher body mass index, lower platelet count, and greater hepatic steatosis (P < .0001). CONCLUSIONS: In patients with chronic hepatitis C and advanced fibrosis, risk of clinical complications and fibrosis progression during 3.5 years can be predicted using baseline laboratory tests and histologic data. Our models may be useful in counseling patients and determining the frequency of monitoring.

Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C.

UNLABELLED: Higher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment. Participants were followed for 3.8 years for clinical outcomes and, for those without cirrhosis, a 2-point increase in Ishak fibrosis score on protocol biopsies. At baseline, higher coffee consumption was associated with less severe steatosis on biopsy, lower serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, alpha-fetoprotein, insulin, and homeostatic model assessment (HOMA2) score, and higher albumin (P < 0.05 for all). Two hundred thirty patients had outcomes. Outcome rates declined with increasing coffee intake: 11.1/100 person-years for none, 12.1 for less than 1 cup/day, 8.2 for 1 to fewer than 3 cups/day, and 6.3 for 3 or more cups/day (P-trend = 0.0011). Relative risks (95% confidence intervals) were 1.11 (0.76-1.61) for less than 1 cup/day; 0.70 (0.48-1.02) for 1 to fewer than 3 cups/day; and 0.47 (0.27-0.85) for 3 or more cups/day (P-trend = 0.0003) versus not drinking. Risk estimates did not vary by treatment assignment or cirrhosis status at baseline. Tea intake was not associated with outcomes. CONCLUSION: In a large prospective study of participants with advanced hepatitis C-related liver disease, regular coffee consumption was associated with lower rates of disease progression.

Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease.

BACKGROUND & AIMS: Although the incidence of hepatocellular carcinoma (HCC) is increasing in the United States, data from large prospective studies are limited. We evaluated the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) cohort for the incidence of HCC and associated risk factors. METHODS: Hepatitis C virus-positive patients with bridging fibrosis or cirrhosis who did not respond to peginterferon and ribavirin were randomized to groups that were given maintenance peginterferon for 3.5 years or no treatment. HCC incidence was determined by Kaplan-Meier analysis, and baseline factors associated with HCC were analyzed by Cox regression. RESULTS: 1,005 patients (mean age, 50.2 years; 71% male; 72% white race) were studied; 59% had bridging fibrosis, and 41% had cirrhosis. During a median follow-up of 4.6 years (maximum, 6.7 years), HCC developed in 48 patients (4.8%). The cumulative 5-year HCC incidence was similar for peginterferon-treated patients and controls, 5.4% vs 5.0%, respectively (P= .78), and was higher among patients with cirrhosis than those with bridging fibrosis, 7.0% vs 4.1%, respectively (P= .08). HCC developed in 8 (17%) patients whose serial biopsy specimens showed only fibrosis. A multivariate analysis model comprising older age, black race, lower platelet count, higher alkaline phosphatase, esophageal varices, and smoking was developed to predict the risk of HCC. CONCLUSIONS: We found that maintenance peginterferon did not reduce the incidence of HCC in the HALT-C cohort. Baseline clinical and laboratory features predicted risk for HCC. Additional studies are required to confirm our finding of HCC in patients with chronic hepatitis C and bridging fibrosis.

Interpretation of positive transcription-mediated amplification test results from polymerase chain reaction-negative samples obtained after treatment of chronic hepatitis C.

UNLABELLED: The Siemens VERSANT transcription-mediated amplification (TMA) assay is extremely sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of 180 subjects in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained virological response (SVR) at week 72 also had TMA-positive results from the same blood draw; six were positive on repeat testing. We report the follow-up on these 11 patients, and the reproducibility of TMA test results from PCR-negative samples in relationship to antiviral treatment outcome. Peginterferon and ribavirin treatment was initiated in 1145 prior interferon nonresponders with advanced hepatic fibrosis. Treatment was continued for 48 weeks if patients had undetectable HCV RNA by PCR at treatment week 20. Frozen serum samples from weeks 12, 20, 24, 48, and 72 were subsequently tested by TMA. Nine of the 11 patients returned for testing (median, 30 months after the week 72 visit), and all had undetectable HCV RNA by TMA and PCR. Among 759 PCR-negative samples obtained during treatment that were tested twice by TMA, 17% overall exhibited consistently positive results, and 21% exhibited inconsistently positive results. SVR was more likely if TMA was consistently negative than if consistently or inconsistently positive. With continued treatment, patients with inconsistently positive TMA results were more likely to become TMA-negative than TMA-positive (P < 0.0001). CONCLUSION: In PCR-negative samples, positive TMA results may indicate the presence of low levels of HCV RNA. However, because patients with positive TMA results may achieve SVR, management decisions during therapy should not be based on a single positive TMA test result.

Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial.

Herbal products, used for centuries in Far Eastern countries, are gaining popularity in western countries. Surveys indicate that persons with chronic hepatitis C (CHC) often use herbals, especially silymarin (milk thistle extract), hoping to improve the modest response to antiviral therapy and reduce side effects. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial, involving persons with advanced CHC, nonresponders to prior antiviral therapy but still willing to participate in long-term pegylated interferon treatment, offered the opportunity to examine the use and potential effects of silymarin. Among 1145 study participants, 56% had never taken herbals, 21% admitted past use, and 23% were using them at enrollment. Silymarin constituted 72% of 60 herbals used at enrollment. Among all participants, 67% had never used silymarin, 16% used it in the past, and 17% used it at baseline. Silymarin use varied widely among the 10 participating study centers; men were more frequent users than women, as were non-Hispanic whites than African Americans and Hispanics. Silymarin use correlated strongly with higher education. No beneficial effect of silymarin was found on serum alanine aminotransferase or hepatitis C virus (HCV) RNA levels. Univariate analysis showed significantly fewer liver-related symptoms and better quality-of-life parameters in users than nonusers, but after reanalysis adjusted for covariates of age, race, education, alcohol consumption, exercise, body mass index, and smoking, only fatigue, nausea, liver pain, anorexia, muscle and joint pain, and general health remained significantly better in silymarin users. In conclusion, silymarin users had similar alanine aminotransferase and HCV levels to those of nonusers but fewer symptoms and somewhat better quality-of-life indices. Because its use among these HALT-C participants was self-motivated and uncontrolled, however, only a well-designed prospective study can determine whether silymarin provides benefit to persons with chronic hepatitis C.