Randomized controlled trial of pegylated interferon-alfa 2a and ribavirin in treatment-naive chronic hepatitis C genotype 6.

UNLABELLED: Hepatitis C virus (HCV) genotype is an important criteria in determining duration of therapy and predictor of sustained virologic response (SVR) to pegylated interferon (PEG IFN) and ribavirin (RBV) therapy. Optimal duration of therapy for patients with HCV genotype 6 is not known. We conducted a multicenter, open-label randomized controlled trial of patients with HCV genotype 6 at five gastroenterology clinics in the western U.S. Patients were stratified by viral load and histologic stage and assigned to receive PEG IFN-α2a 180 µg subcutaneously weekly and weight-based oral RBV 800 to 1,200 mg daily for 24 or 48 weeks. Primary outcome measurement was SVR rate by intention-to-treat analysis. From February 2005 to October 2007 a total of 60 patients (age 51 ± 10 years, 47% male, log HCVRNA 6.3 ± 1.1 IU/mL) were enrolled: 27 patients to 24 weeks and 33 patients to 48 weeks of therapy. In the 24-week and 48-week groups, 96% and 97% achieved early virologic response (P = 0.90); 89% versus 94% achieved end of therapy virologic response (P = 0.48). SVR was achieved in 70% versus 79% of patients assigned to 24 weeks versus 48 weeks (P = 0.45). Rapid virologic response (RVR) was a significant predictor of SVR in the 48-week group and trending towards significance in the 24-week group: 82% and 83% of those with RVR achieved SVR versus 33% and 29% for the 24-week and 48-week groups, respectively (P = 0.07 and P = 0.02). CONCLUSION: There was no significant difference in SVR rates in patients with HCV genotype 6 treated with PEG IFN-α2a and RBV for 24 versus 48 weeks.

Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity.

UNLABELLED: Studies using surrogate estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 +/- 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI > or = 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation coefficients were highest in the obese. I-AUC had the highest correlation among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of < or =3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within-person variation in the obese (standard deviation = 0.77 higher than normal-weight, 95% confidence interval = 0.25-1.30, P = 0.005). CONCLUSION: Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV.

Adherence to screening for hepatocellular carcinoma among patients with cirrhosis or chronic hepatitis B in a community setting.

BACKGROUND: Screening for hepatocellular carcinoma (HCC) has been shown to improve survival via earlier cancer detection. Although HCC screening is considered standard of care in the USA, little is known of the adherence to this practice, especially in a community setting. AIMS: Our primary goal was to evaluate adherence to HCC screening and to find predictors of screening adherence in a community setting. Our secondary objective was to determine the impact of screening on survival. METHODS: We studied a cohort of 557 consecutive patients at high risk for HCC: patients with cirrhosis and older chronic hepatitis B (CHB) patients without cirrhosis (≥45 years old). Patients initiated screening 1/2001-1/2005 and were monitored ≥12 months to 12/2008 in two community gastroenterology clinics in Northern California. HCC screening was categorized into four groups based on combined frequency of serum alpha-fetoprotein and imaging: optimal, suboptimal, poor, and no screening. RESULTS: About 40.6% of our cohort received poor or no screening. Noncirrhotic CHB patients had worse screening than cirrhotic patients. Multivariate analysis revealed that patients with a greater number of clinical visits per year were 3.4 times more likely to have regular screening than patients with fewer clinical visits per year (P<0.001). There was a trend for association between HCC screening and greater access to curative treatment. CONCLUSION: Since more frequent clinic visits is a strong independent predictor of improved screening adherence, regular routine clinic visits may help improve adherence to HCC screening, which may also lead to improved clinical outcomes.

Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels.

OBJECTIVES: At present there is no clear consensus on how patients with chronic hepatitis B (CHB), high serum hepatitis B virus (HBV) DNA, and normal alanine aminotransferase (NLALT) levels should be managed. This study hypothesizes that a significant proportion of such patients may have histological disease. METHODS: We carried out a retrospective study of 101 consecutive treatment-naive patients with CHB who underwent liver biopsies at a community gastroenterology clinic and had high HBV DNA and NLALT (< or = 40 U/l) levels at the time of biopsy. All patients were Asians. ALT levels were observed for a period of time before liver biopsy and were used to classify patients into two groups, namely those with only NLALT levels and those with fluctuating ALT (FLALT) levels. All patients had at least two ALT measurements during this period of time. Significant histology was defined as stage > or = 2 fibrosis or stage 1 fibrosis plus grade > or = 2 inflammation using the Batts-Ludwig scoring system. RESULTS: In patients with NLALT levels, the proportions of those with significant histology were 0, 22, and 45% for age < or = 35, 36-50, and >50 years, respectively (n=11, n=27, n=19; P=0.033). In patients who had FLALT levels, the corresponding proportions were 22, 42, and 69% (n=9, n=22, n=13; P=0.091). After adjustments for gender, hepatitis B e antigen (HBeAg) status, and mean pre-biopsy HBV DNA levels, significant predictors of histological disease were older age (odds ratio (OR)=6.2 for age 36-50 years and OR=17.6 for age >50 years compared with age < or = 35 years, P=0.041 and P=0.003, respectively) and FLALT levels (OR=3.6, P=0.008). Sub-analysis of patients with NLALT levels using lower cutoffs (30 U/l for men and 19 U/l for women) showed similar trends. CONCLUSIONS: Patients with CHB, high HBV DNA, and NLALT levels and aged more than 35 years or those with FLALT levels may have significant histological disease (22-70%).

Prevalence of colorectal neoplasms in Asian Americans.

PURPOSE: To determine the yield of colonoscopy in a predominantly Asian American gastroenterology practice in California from 8/2003 to 2/2005. RESULTS: A total 2,723 subjects were included: 87% were Asian and 13% were non-Asian. Advanced neoplasia prevalence was 12% in Asian men and 9% in non-Asian men (P = 0.21), and 8% and 7% in women (P = 0.62). Similar results were found in asymptomatic patients (13% and 13%, P = 0.99, for men; 8% and 6%, P = 0.46, for women). Factors associated with presence of advanced neoplasia were total number of polyps and presence of right-sided lesions. Asian men were more likely to have neoplasia overall compared with non-Asian men with odds ratio (OR) of 2.14 (1.23-3.72); however, there were no significant differences in the prevalences of advanced neoplasia in the two groups. CONCLUSIONS: Colorectal neoplasia is as prevalent in Asian Americans and preventive guidelines for colorectal cancer should also be advocated for this ethnic group.

Low proportion of Barrett's esophagus in Asian Americans.

OBJECTIVES: To determine the proportion of Barrett's esophagus (BE) in Asians versus non-Asians and the predictors of BE in patients with upper gastrointestinal (GI) symptoms. METHODS: We performed a cross-sectional study to determine the proportion of BE from all consecutive patients who underwent esophagogastroduodenoscopy (EGD) for various indications at an outpatient, community-based gastroenterology practice in northern California from February 2000 to September 2006. BE was defined as endoscopically recognized presence of salmon-pink mucosa in the distal esophagus and intestinal metaplasia on biopsy. We also performed a nested case-control study to determine potential predictors of BE. RESULTS: In total, 5,293 patients were reviewed. BE was more common in non-Asians (31/1464, 2.1%) than Asians (29/3829, 0.76%) (P < 0.001). In multivariate analysis controlling for increasing age, male gender, ethnicity, smoking, and alcohol, the strongest predictor of the presence of BE was non-Asian ethnicity (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.85-6.85), followed by male gender (OR 2.68, 95% CI 1.32-5.45). CONCLUSION: BE is uncommon in Asian Americans; non-Asian ethnicity and male gender are significant independent predictors of BE.

Higher rate of sustained virologic response in chronic hepatitis C genotype 6 treated with 48 weeks versus 24 weeks of peginterferon plus ribavirin.

OBJECTIVES: Infection with hepatitis C virus (HCV) genotype 6 is common in patients from parts of China and Southeast Asia. No study to date has examined the treatment response to peginterferon and ribavirin (PEG IFN + RBV) in these patients, or the effects of treatment duration on sustained virologic response (SVR) rates. METHODS: We performed a retrospective study of 190 consecutive Asian-American patients who were diagnosed with HCV genotype 6 at a gastroenterology clinic in northern California between 2001 and 2004, 66 of whom were treatment-naïve and subsequently completed 24 wk of IFN + RBV or PEG IFN + RBV or 48 wk of PEG IFN + RBV therapy. The primary outcome was SVR. RESULTS: There was no statistical difference in SVR of 31 patients treated with 24 wk of IFN + RBV and in 23 patients treated with 24 wk of PEG IFN + RBV (51.6%vs 39%, P= 0.363). The SVR in 12 patients treated with 48 wk of PEG IFN + RBV was significantly higher than that in those treated for only 24 wk (75%vs 39%, P= 0.044). CONCLUSIONS: Treatment-eligible patients with HCV genotype 6 should be treated with a full course of 48 wk as tolerated. Larger prospective studies of patients with HCV genotype 6 are needed to confirm the optimal treatment duration with PEG IFN + RBV.