Bhupinder S. Anand

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.

Influence of endoscopic biopsy forceps characteristics on tissue specimens: results of a prospective randomized study

BACKGROUND A large variety of endoscopic biopsy forceps are commercially available. However, little is known regarding the influence of forceps characteristics such as disposability, size, shape, and presence of a needle on the adequacy of the specimens for histologic diagnosis. Our aim was to analyze in a prospective, randomized, pathologist-blinded study the performance of different biopsy forceps. METHODS Twelve biopsy forceps were tested, 6 each at upper endoscopy and colonoscopy. Two biopsy specimens were obtained with each forceps, for a total of 12 specimens per patient. The tissue samples were examined for the following parameters: weight (mg), size (mm3), depth, crush artifact, sheering effect, and adequacy of the specimens for histologic information (0 = inadequate, 1 = suboptimal, and 2 = adequate). RESULTS Fifty-five patients undergoing routine upper or lower gastrointestinal endoscopy were included in the study, and a total of 624 tissue samples were available for analysis. Overall, disposable forceps provided specimens of greater size and depth. At upper endoscopy, alligator-shaped forceps improved the depth of the sample as did the absence of a needle within the cup. These factors, however, had no impact on the specimens obtained at colonoscopy. When the adequacy of the specimens was assessed for histologic diagnosis, no significant difference was noted between any of the individual forceps, although collectively oval-shaped forceps were superior to alligator-shaped forceps at colonoscopy. CONCLUSIONS The biopsy forceps currently available in the market are equally efficient in providing histologic diagnosis. The primary consideration when selecting an endoscopic biopsy forceps, therefore, should be the cost and ease of use and not any perceived advantage in performance.

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.

Assessment of Liver Histology in Chronic Alcoholics with and Without Hepatitis C Virus Infection

Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection. The histological appearances of the liver in patients with alcoholic liver disease and HCV infection are well described. However, liver histology in individuals with dual pathology, both chronic alcohol abuse and HCV infection, is less well understood. The purpose of the present study was to examine this issue and to determine if there is any correlation between specific histological features and the serum biochemical abnormalities seen in these patients. Eighty-six chronic alcoholics, 65 with HCV infection and 21 uninfected subjects, were included in the study. All patients had history of heavy alcohol abuse (consuming 80 g or more of ethanol a day for at least 10 years). The following data were collected on each patient: demographic information (age, gender, race), the amount and duration of alcohol intake, biochemical results, and liver biopsy abnormalities including the histological activity index (HAI) score. HCV-infected alcoholics were younger (P = 0.05) and were more often African American than Caucasian (P < 0.01). Alcohol consumption was significantly greater in uninfected alcoholics compared to those with HCV infection (P < 0.05). Liver histology in subjects with HCV infection showed higher HAI scores for intralobular necrosis (P = 0.008) and periportal inflammation (P = 0.004). Features of “chronic hepatitis” and focal lymphoid aggregates were more frequent in HCV-infected alcoholics (P = 0.001 for each). By contrast, cirrhosis was present in a higher proportion of uninfected alcoholics compared to those with HCV infection (P = 0.05). Histological findings of hepatic fibrosis and total HAI score showed a significant correlation with serum albumin and platelet count in HCV-infected alcoholics. Chronic alcoholics with HCV infection have specific histological appearances that can usually help distinguish these patients from uninfected alcoholics. Correlation analysis indicates that of the various laboratory tests, serum albumin and platelet counts are the best predictors of the severity of liver damage at histology. In chronic alcoholics, the development of cirrhosis is related more to the amount of alcohol consumed than to the presence of HCV infection.

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.

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.

Premorbid Hair Growth over the Trunk and Severity of Alcohol-Related Liver Disease

It is unclear why only a minority (<15%) ofalcoholics develop liver disease. No predisposing hostfactor other than gender (women are more susceptiblethan men) has been identified. The present study was carried out to examine the association ofanother host factor, hair growth over the trunk, andalcoholic liver disease. Forty-four chronic alcoholabusers were categorized into group I (scanty hairgrowth) and group II (profuse hair growth) based onpremorbid hair distribution over the trunk. The resultsof laboratory tests, liver histology, and incidence ofportal hypertension were compared between the two groups. There were 21 patients in group I and23 in group II. The mean (±SD) daily alcoholconsumption was greater in group II (230 ± 146 g)vs group I patients (152 ± 56 g; P < 0.05), aswas the duration of alcohol abuse (17.3 ± 7.4 vs 11.9 ± 4.9years; P < 0.01). Despite lower alcohol consumption,liver tests showed greater derangement in group Icompared to group II patients. At histology, severeforms of liver damage were seen more frequently in group I vs groupII patients (P < 0.001). Our results indicate a closeassociation between the premorbid truncal hair growthand severity of alcoholic liver disease. These findings provide an easily recognizable clinical signidentifying individuals at increased risk of developingalcoholrelated liver damage.

Comparison of truncal hair distribution in alcoholic liver disease and alcohol‐related chronic pancreatitis

Abstract The present study shows that scanty hair distribution over the trunk is a specific finding in patients with alcoholic liver disease (ALD), and is not seen in alcoholic pancreatitis. This observation not only provides a useful clinical marker of individuals at increased risk of developing alcohol‐related liver disease, but from the pathogenetic viewpoint, it suggests that at the tissue level, the male sex hormones protect the liver against ethanol‐related damage.

Flexible sigmoidoscopy has poor predictive value for neoplasms proximal to the splenic flexure

Flexible sigmoidoscopy has poor predictive value for neoplasms proximal to the splenic flexure