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This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 μg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [

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; 1st generation DAA (telaprevir or boceprevir) + P + R; 2nd generation DAA (sofosbuvir or simeprevir) + P + R; 2nd generation DAA + R; two 2nd generation DAA + R; and two 2nd 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.

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.

It is unclear why only a minority (

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.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.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.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.

Background and Aims: Current treatment for genotype (GT) 2 or 3 hepatitis C virus infection is pegylated interferon and ribavirin (RBV) 800mg/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 16wk) 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.

Since the discovery of the hepatitis C virus (HCV), extensive literature has emerged on alcohol and HCV interaction.To understand the impact of alcohol and HCV infection on the severity of liver disease and the mechanisms of interaction between the two.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.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.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.

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.

Several age-related changes occur in the structure and functions of the liver. The volume of the liver decreases, despite an increase in the size of hepatocytes, suggesting loss of liver cells. There are decreases in hepatic blood flow, the synthesis of urea and cholesterol, and the metabolism of drugs. Moreover, the regenerative capacity of liver becomes less efficient. Certain caveats are important when treating older patients with liver disease. Strict dietary restrictions, such as a low protein diet, should be avoided in the elderly (unless the patient is encephalopathic) because these patients are often undernourished to start with. Similarly, strict salt restriction should be enforced with caution, since it makes food less palatable and may take away what little desire such patients have to eat. Diuretic doses should be adjusted carefully because of greater risks of azotaemia and electrolyte disturbances in the elderly. Extra vigilance should be exercised in the early detection of infections that are more likely to occur in patients with cirrhosis. For example, spontaneous bacterial peritonitis can be missed in the elderly because of poor systemic (fever, abdominal tenderness) and laboratory responses (leucocytosis). In patients presenting with acute variceal bleeding, it is better to err on the side of underhydration than overhydration because of the risk of congestive heart failure. Vasopressin should be avoided in the elderly, since this drug has a high probability of precipitating an ischaemic event. Older patients do not tolerate beta-blockers as well as younger individuals and may require other treatment strategies for the prevention of variceal rebleeding episodes. Hepatic encephalopathy, especially the milder form, needs careful assessment because it can be easily confused with senile dementia syndromes. Cirrhosis is a premalignant condition and patients are at increased risk of developing hepatocellular carcinoma (HCC), a tumour seen predominantly in the elderly. All patients with cirrhosis should be maintained on a lifelong screening programme consisting of a 6-monthly assessment of alpha-fetoprotein and an imaging study, since early detection provides the only hope for cure of HCC. The only definitive treatment of cirrhosis is liver transplantation. Advanced age is not a contraindication to transplantation, and survival in older patients (aged60 years) is comparable to that in younger individuals.

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.

To determine the optimum dose of ispaghula husk in patients with irritable bowel syndrome (IBS) and to assess the correlation, if any between the relief in patients' symptoms and the whole gut transit time, and the increase in stool weight, a two part study was carried out. In part 1, 14 male patients were given ispaghula husk in increasing doses of 10 g, 20 g, and 30 g a day for a duration of 17 days each (14 days of study period + three days of stool collection). Ten patients completed the trial. The symptom score improved significantly with all the three doses of ispaghula. Both 20 g and 30 g doses of ispaghula were superior to the 10 g dose but there was no significant difference between the 20 g and 30 g doses. There was a significant (p less than 0.001) increase in the daily stool weight with 10 g dose of fibre with further significant increases with the 20 g and 30 g doses. A positive correlation was seen between the improvement in the symptom score and the increase in stool weight with the 10 g dose of ispaghula but not with the 20 g and 30 g doses. Whole gut transit time remained fairly constant throughout the study period and there was no relationship with either the dose of ispaghula, the alteration in stool weight, or the improvement in the patients symptoms. Ten patients completed part 2 of the study in which ispaghula husk was given in the same dose (10 g, 20 g, and 30 g) but in a random order and with a "washout" period of one week between individual doses. Again all the three doses of ispaghula produced a significant improvement in the symptoms; 20 g and 30 g doses were equally effective and both were significantly superior to the 10 g dose. Assessed individually, all the three symptoms improved significantly; improvement in constipation and pain abdomen was more pronounced than diarrhoea. It is concluded that the optimum dose of ispaghula husk in irritable bowel syndrome is 20 g per day. There is some correlation between the increase in stool weight and the improvement in symptom score but the whole gut transit time remains unchanged despite alterations in stool weight and patients' symptoms.