Impact of all oral anti-hepatitis C virus therapy: A meta-analysis.

AIM: To investigate the efficacy, safety, and cost of treatment of direct acting antivirals (DAAs) with and without peg interferon alfa2a (P), and/or ribavirin (R) in treating hepatitis C virus (HCV) genotype 1 patients. METHODS: MEDLINE was searched for randomized controlled trials (RCT) using DAAs for HCV treatment. Phase 1 trials and studies with investigational drugs on genotype 2 or 3, and on human immunodeficiency virus patients were excluded. Data were pooled for sustained virologic response (SVR), serious adverse effects, and drug discontinuation rate on various treatment arms in trials: P + R; 1(st) generation DAA (telaprevir or boceprevir) + P + R; 2(nd) generation DAA (sofosbuvir or simeprevir) + P + R; 2(nd) generation DAA + R; two 2(nd) generation DAA + R; and two 2(nd) gen DAA. Data were analyzed separately for each arm for treatment naive and non-responders (NR) to previous treatment. The cost of treatment with each regimen for achieving one SVR was also compared. RESULTS: Twenty three RCTs (n = 9354, 62% male, 11% cirrhosis) were analyzed. All oral (P free) regimens with combination of 2 DAA achieved SVR above 95%. The cost of treatment to achieve an SVR with DAA based regimens was lower for NR compared to P+R regimen. However, the cost per SVR remained higher for treatment naive patients. CONCLUSION: Second generation and emerging DAAs are promising agents in HCV treatment, with a very high level of safety and efficacy. An important drawback is their high cost. However, the present meta-analysis shows that the cost per SVR for non responders (but not for naive patients) was lower compared to P + R. This finding together with the superior safety profile and better compliance makes these drugs highly attractive. It is possible that further reduction in treatment duration may make them even more cost effective.

Impact of race on colorectal cancer.

BACKGROUND: Several studies have shown that colorectal cancer runs a more severe course in blacks compared with whites. Black patients tend to have more advanced disease at diagnosis and are more likely to die of cancer than are white patients. The present study was carried out to compare the characteristics and outcomes of colon cancer in blacks and whites in a Veterans Affairs Medical Center, where patients are expected to receive similar treatment irrespective of race. METHODS: The database of the Veterans Affairs Medical Center was searched for all patients with a histologic diagnosis of colon cancer diagnosed since 1996. Detailed information on patient and tumor characteristics was obtained. In addition the type of treatment and outcome was analyzed. RESULTS: A total of 300 subjects were included in the study. They comprised 205 white and 95 black patients. There was no difference in age at presentation between the 2 groups. Blacks were more likely to have anemia (P = .005) and rectal bleeding (P < .001) than were whites. However there was no difference between the 2 groups with respect to the histologic grade of the tumor, the extent of disease at presentation, the proportion of patients receiving curative surgery, and the time to death after diagnosis. CONCLUSIONS: There was no racial difference in the treatment outcome of colon cancer in patients treated at a Veterans Affairs Medical Center. These findings indicate that if patients receive similar treatment, the racial background of an individual does not have any impact on the severity of disease at presentation and the outcome of treatment.

Tailoring treatment duration to 12 to 16 weeks in hepatitis C genotype 2 or 3 with rapid virologic response: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Current treatment for genotype (GT) 2 or 3 hepatitis C virus infection is pegylated interferon and ribavirin (RBV) 800 mg/d for 24 weeks. This meta-analysis was carried out to assess whether the treatment duration can be reduced in patients with rapid virologic response (RVR) METHODS: Literature was searched for studies comparing short-term (12 to 16 wk) and 24 weeks treatment in GT 2 or 3 with RVR. RESULTS: Six studies (n=2434) were included and data on end-of-treatment response (ETR), sustained virologic response (SVR), and relapse rates (RR) were obtained. Pooled odds ratio (95% CI) for SVR and RR were 0.54 (0.35-0.85; P=0.008) and 3.12 (1.99-4.91; P<0.00001) favoring 24 weeks of treatment. Reducing treatment duration to 12 to 16 weeks and retreating relapses for 24 weeks was cost-effective. CONCLUSIONS: Reducing treatment duration to 12 to 16 weeks for GT 2 or 3 HCV patients with RVR is associated with a lower SVR and a higher RR. Advantages of short-term treatment include better patient compliance, lower rate of adverse effects, and cost. Short-term treatment may be an option for patients unable to tolerate treatment. Further studies are needed to identify factors predicting relapse with short-term treatment in GT 2 or 3 patients with RVR.

Mechanisms of synergy between alcohol and hepatitis C virus.

BACKGROUND: Since the discovery of the hepatitis C virus (HCV), extensive literature has emerged on alcohol and HCV interaction. GOAL: To understand the impact of alcohol and HCV infection on the severity of liver disease and the mechanisms of interaction between the two. STUDY: Of 1269 articles (1991 to 2006) searched through MEDLINE and cited cross references, 133 were thoroughly reviewed to assess: (a) prevalence of combined alcohol use and HCV, (b) severity of liver disease (c) treatment response, and (d) mechanisms of interaction between HCV and alcohol. Data on study design, patient demographics, diagnostic tests used, and study outcomes were extracted for critical analysis. RESULTS: Prevalence of HCV is 3-fold to 30-fold higher in alcoholics compared with the general population. Patients with HCV infection and alcohol abuse develop more severe fibrosis with higher rate of cirrhosis and hepatocellular cancer compared with nondrinkers. Increased oxidative stress seems to be the dominant mechanism for this synergism between alcohol and the HCV. Abstinence is the key to the management of liver disease due to HCV and alcohol. Data have shown that lower response rates to interferon in alcoholics with HCV infection are likely due to noncompliance. CONCLUSIONS: Alcoholics with HCV infection have more severe liver disease compared with nondrinkers. Patients should be encouraged to enroll in rehabilitation programs so as to improve treatment adherence and response.

Alcohol use and treatment of hepatitis C virus: results of a national multicenter study.

BACKGROUND & AIMS: Patients with hepatitis C virus (HCV) infection who use alcohol have been excluded from clinical trials; therefore, outcomes with antiviral therapy are unknown. The aim of the study was to determine the impact of alcohol use on HCV treatment outcomes. METHODS: Subjects using alcohol were categorized as follows: no alcohol versus regular alcohol use, quantity consumed (none, <6 drinks/day, >/=6 drinks/day), CAGE score <2 or >/=2, and recent alcohol use (past 12 months). Patients were treated with interferon plus ribavirin. RESULTS: A total of 4061 subjects were enrolled, and 726 (18%) received treatment. Alcohol use (past and within 12 months) reduced treatment candidacy. Past alcohol use did not affect the end-of-treatment response, sustained virologic response (SVR), and treatment discontinuation rates. However, recent alcohol use resulted in higher treatment discontinuation (40% vs 26%; P = .0002) and tended to reduce the SVR (14% vs 20%; P = .06), but when patients who discontinued treatment were excluded from analysis, the trend in favor of nondrinkers for SVR disappeared (25% vs 23%). These findings were also consistent in subgroup analyses on race and genotype. CONCLUSIONS: Eligibility for anti-HCV treatment was reduced in past and recent drinkers. Recent alcohol use was associated with increased treatment discontinuation and lower SVR. However, patients who use alcohol and completed the treatment had a response comparable to that of nondrinkers. Patients with a history of alcohol use should not be excluded from HCV therapy. Instead, additional support should be provided to these patients to ensure their ability to complete treatment.

Tubulovillous adenoma of anal canal: a case report.

Tumors arising from the anal canal are usually of epithelial origin and are mostly squamous cell carcinoma or basal cell carcinoma. We present a case of benign anal adenomas arising from the anus, an extremely rare diagnosis. A 78-year-old white man presented with rectal bleeding of several months duration. Examination revealed a 4 cm friable mass attached to the anus by a stalk. At surgery, the mass was grasped with a Babcock forceps and was resected using electrocautery. Microscopic examination revealed a tubulovillus adenoma with no areas of high grade dysplasia or malignant transformation. The squamocolumnar junction was visible at the edges of the lesion confirming the anal origin of the tumor. We believe the tubulovillus adenoma arose from either an anal gland or its duct that opens into the anus. Although seen rarely, it is important to recognize and treat these tumors at an early stage because of their potential to transform into adenocarcinoma.

Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival.

BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. RESULTS: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P = .371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P = .337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis.

Elevated prevalence of hepatitis C infection in users of United States veterans medical centers.

Several studies suggest veterans have a higher prevalence of hepatitis C virus infection than nonveterans, possibly because of military exposures. The purpose of this study was to estimate the prevalence of anti-hepatitis C antibody and evaluate factors associated with infection among users of Department of Veterans Affairs medical centers. Using a two-staged cluster sample, 1288 of 3863 randomly selected veterans completed a survey and underwent home-based phlebotomy for serological testing. Administrative and clinical data were used to correct the prevalence estimate for nonparticipation. The prevalence of antihepatitis C antibody among serology participants was 4.0% (95% CI, 2.6%-5.5%). The estimated prevalence in the population of Veterans Affairs medical center users was 5.4% (95% CI, 3.3%-7.5%) after correction for sociodemographic and clinical differences between participants and nonparticipants. Significant predictors of seropositivity included demographic factors, period of military service (e.g., Vietnam era), prior diagnoses, health care use, and lifestyle factors. At least one traditional risk factor (transfusion or intravenous drug use) was reported by 30.2% of all subjects. Among those testing positive for hepatitis C antibody, 78% either had a transfusion or had used injection drugs. Adjusting for injection drug use and nonparticipation, seropositivity was associated with tattoos and incarceration. Military-related exposures were not found to be associated with infection in the adjusted analysis. In conclusion, the prevalence of hepatitis C in these subjects exceeds the estimate from the general US population by more than 2-fold, likely reflecting more exposure to traditional risk factors among these veterans.

Assessment of correlation between serum titers of hepatitis C virus and severity of liver disease.

AIM: The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels. Moreover, a direct association has been observed between serum titers of HCV and transmission rates of the virus. The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. METHODS: Fifty patients with HCV infection were included in the study. These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics. Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique. Linear regression analysis was performed between serum viral titers and liver tests. In addition, for the purpose of comparison, the subjects were divided into two groups: those with low viral titers (< or = 50 genome mEq/mL) and high titers (> 50 mEq/mL). RESULTS: All subjects were men, with a mean +/- SD age of 47 +/- 7.8 years. The mean HCV RNA level in the blood was 76.3 x 10(5) +/- 109.1 genome equivalents/mL. There was no correlation between HCV RNA levels and age of the patients (r = 0.181), and the history or amount (g/d) of alcohol consumption (r = 0.07). Furthermore, no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r = 0.175), bilirubin (r = 0.217), ALT (r = 0.06) and AST (r = 0.004) levels. Similarly, no significant difference was observed between patients with low viral titers and high titers with respect to any of the parameters. CONCLUSION: Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus. These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.

Racial differences in response rates to consensus interferon in HCV infected patients naive to previous therapy.

BACKGROUND: Despite a rapid evolution in the treatment of Hepatitis C (HCV), response to therapy among different racial and ethnic groups is poorly characterized. STUDY: Three hundred and thirty HCV infected patients naive to previous therapy received induction therapy followed by every other day dosing with consensus interferon. Greater than 30% of treated patients were not white, allowing comparison of response among different races/ethnicities and genotypes. RESULTS: An overall sustained virologic response (SVR) was achieved in 24% of white, 12% of Hispanic, and 4% of AA patients (P = 0.003 white vs. non-white). 15% of white and 13% of Hispanic Genotype 1 patients achieved an SVR; 2% of AA patients achieved an SVR (P = 0.001 AA vs. non AA). Surprisingly, an SVR of 50% and 40% was achieved by AA and White Genotype 2 patients, compared with 10% in Hispanic patients (P = 0.001). CONCLUSION: Significant differences in response rates to induction therapy followed by every other day dosing with consensus Interferon was observed when comparing white to non-white patients, particularly when comparing response rates by genotype. These observations reinforce the requirement that prospective studies that enroll a significant percentage of non-whites are needed to adequately characterize response rates to anti-HCV directed therapy.