Anand Bs

Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection

BACKGROUND:Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment.METHODS:We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician.RESULTS:Overall, 32.2% (95% CI, 30.8–33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2–42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24–25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85–13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70–13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42–16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0–78.3%) agreed to be treated and multivariable analysis showed that persons ≥50 yr of age (OR = 1.37; 95% CI, 1.07–1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08–1.93) were more likely to decline treatment.CONCLUSIONS:The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.

Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects

OBJECTIVES:In previous studies on rats, we have shown that aspirin (ASA)-induced injury to the gastric mucosa is markedly reduced or completely abolished if ASA is chemically associated with the phospholipid, phosphatidylcholine (PC). We have also shown that the protective effect of PC does not influence the ability of ASA to inhibit mucosal cyclooxygenase (COX) activity in the stomach and other tissues. We therefore sought to assess the effect of PC-associated ASA (ASA/PC) on the gastric mucosa of normal volunteers and to compare the results with the use of ASA alone.METHODS:Sixteen normal healthy subjects were administered ASA or ASA/PC in a randomized, double-blind, crossover study. The subjects received ASA in a dose of 650 mg three times a day for 3 days or an equivalent dose of ASA chemically associated with PC. Endoscopy was performed at baseline and again on the morning of day 4, after the subjects had taken the final dose of the test drug. On both occasions, antral biopsy specimens were obtained for the assessment of mucosal COX activity and prostaglandin concentration.RESULTS:The number (mean ± SD) of gastric erosions seen with the ASA/PC formulation was significantly less than when ASA was used alone (8.7 ± 10.7 vs 2.9 ± 4.3; p < 0.025). A similar trend was seen in the duodenum but the difference was statistically not significant. The antral mucosal COX activity, as well as the level of prostaglandin 6-keto PGF1α, were reduced significantly (80–88%) and to a similar extent by both ASA and ASA/PC.CONCLUSIONS:The present study shows that acute aspirin-induced damage to the gastric mucosa can be reduced by chemically associating ASA with PC. The mechanism of mucosal protection provided by this compound is not related to any alteration in the ability of ASA to inhibit mucosal COX activity. We believe this protection is attributable to the maintenance of the defensive hydrophobic barrier of the gastric mucosa.

Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: Exploratory analysis from the UNOS database

Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004‐2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow‐up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five‐year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (P = 0.97) and 80% and 78% (P = 0.90), respectively. Five‐year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol‐related in any patient. Conclusion: Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long‐term outcome after liver transplantation in patients with alcoholic hepatitis. (HEPATOLOGY 2012)

Chronic hepatitis C in Latinos: natural history, treatment eligibility, acceptance, and outcomes.

OBJECTIVES:The natural history of chronic hepatitis C and treatment response are different between blacks and Caucasians, but little comparable data is available about Latinos.METHODS:A cross-sectional secondary analysis to investigate differences between 421 anti-HCV-positive, treatment-naïve, HCV-viremic Latinos and 2,510 Caucasians in 24 VA medical centers enrolled in a prospective study.RESULTS:Latinos were infected at a younger age and were less likely to have blood contact during combat, surgery, and needle stick injury, but were more frequently HIV coinfected (20.4% vs 3.9%, p < 0.0001) and prior HAV infection (39.9% vs 26.4%, p = 0.0001). Latinos were more likely to be treatment candidates, but less likely to actually initiate treatment. Liver histology (123 Latinos, 743 Caucasians) showed no difference in fibrosis or fibrosis rate, but steatosis (54.7% vs 43.2%, p = 0.038) was more common in Latinos. Eighty-eight Latinos and 481 Caucasians were subsequently treated with interferon-ribavirin: body mass index (BMI), duration of infection, baseline tests, liver histology and genotype distribution were similar. Compared with Caucasians, Latinos discontinued treatment prematurely more often (39.8% vs 28.9%, p = 0.043) and tended to have lower sustained virological response (SVR) rates (14.8% vs 22.5%, p = 0.10). Multivariate analysis found Latino race and history of recent alcohol use to be associated with early treatment discontinuation, whereas genotype and viral load but not ethnicity to be associated with SVR.CONCLUSIONS:Latinos were infected younger, more frequently HIV coinfected, more likely to meet criteria for antiviral therapy yet less likely to initiate treatment and had a trend toward lower SVR rates than Caucasians, but not in severity of liver disease. Latino ethnicity was associated with early discontinuation but not as an independent predictor of SVR.

Assessment of Fatigue and Psychologic Disturbances in Patients with Hepatitis C Virus Infection

Background It is a common clinical impression that fatigue is a frequent, and often debilitating, symptom in patients with chronic hepatitis C virus (HCV) infection. However, despite its obvious clinical importance, several aspects of fatigue, including its relationship with the underlying liver disease and the presence of psychologic disturbances, have not been well examined. Goals The current study was carried out to assess these issues. Study A total of 149 subjects were included in the study and were assigned to one of the following study groups: healthy controls (31), chronic HCV infection (24), combined HCV infection and chronic alcohol abuse (32), alcoholic liver disease (22), and chronic non-liver diseases (40). All subjects were administered investigator-assisted questionnaires designed to analyze the presence and severity of fatigue and psychologic abnormalities. Results The mean (±SD) fatigue scores in patients with chronic HCV infection (140 ± 22.9;p = 0.002), alcoholic liver disease (127 ± 31.4;p < 0.001), mixed (HCV/alcoholic) liver disease (131 ± 29.0;p < 0.001), and chronic non-liver diseases (128 ± 35.9;p = 0.004) were significantly greater compared to with healthy subjects (101 ± 31.8). The total fatigue scores were higher in HCV-infected subjects compared with the other patient groups, but the differences failed to reach statistical significance. Moreover, the fatigue experienced by patients with HCV did not improve with rest as effectively as in the other study groups. All patient groups had higher scores for psychologic disturbances compared with healthy subjects. Conclusions The current study shows that fatigue and psychologic disturbances occur frequently in chronic diseases. The fatigue experienced by patients with HCV infection is more severe and intransigent and responds poorly to relieving factors. Moreover, patients with HCV infection are more depressed and harbor greater feelings of anger and hostility compared with those with non-liver chronic diseases. These observations are important because proper management of the psychologic symptoms may have a favorable impact on the quality of life of patients with HCV infection.

Association Between Hepatitis C Infection and Other Infectious Diseases: A Case For Targeted Screening?

OBJECTIVE:Hepatitis C virus (HCV) shares risk factors and routes of transmission with several other infectious agents. However, the prevalence of comorbid infectious disorders among HCV-infected patients remains unknown. To analyze the association between HCV and several categories of infectious disorders, we carried out a case-control study using information from 172 hospitals contained in the computerized databases of the Department of Veterans Affairs.METHODS:We identified all HCV-infected patients who were hospitalized during 1992–1999. For each case, four control subjects without HCV were randomly chosen from hospitalized patients and were matched with cases on the year of admission. The frequencies of several predefined infectious disease diagnoses were compared between cases and control subjects, and the strength of these associations were assessed in multivariable logistic regression analyses.RESULTS:We identified 34,204 HCV-infected patients (cases) and 136,816 control subjects without HCV. Patients in the case group were younger (48.4 yr vs 59.8 yr), were more frequently nonwhite (38.5% vs 26.5%), and were more likely to have served in Vietnam (68.1% vs 33.0%); all p < 0.0001. Compared with control subjects, patients with HCV had a significantly higher prevalence of other blood-borne virus infections, including HIV (14.1% vs 3.0%) and hepatitis B (22.4% vs 0.7%); immunodeficiency-related infections, including cytomegalovirus (0.6% vs 0.2%), toxoplasmosis (0.3% vs 0.1%), cryptococcosis (0.4% vs 0.1%), and tuberculosis (3.3% vs 1.3%); sexually transmitted diseases, including gonococcus (0.5% vs 0.1%), chlamydia (1.6% vs 0.7%), syphilis (2.0% vs 0.6%), and genital herpes (1.0% vs 0.3%); and bacterial infection, including peritonitis, sepsis, endocarditis, cellulitis, and carbuncles (all p < 0.0001). After excluding potentially immunocompromised patients, including those with HIV, organ transplant, and cirrhosis, HCV remained significantly associated with CMV, cryptococcus, tuberculosis, and sexually transmitted diseases. Similar results were obtained when the analyses were restricted to Vietnam-era veterans.CONCLUSIONS:Several infectious diseases are more common among HCV-infected patients compared with those without HCV infection. These findings support an approach of targeted screening for HCV among patients with these infectious diseases.

Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study

Objective Abdominal obesity has been associated with increased risk of Barretts oesophagus (BE) but the underlying mechanism is unclear. We examined the association between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the risk of BE. Design A case-control study among eligible patients scheduled for elective oesophagastroduodenoscopy (EGD) and in a sample of patients eligible for screening colonoscopy recruited at the primary care clinic. All cases with definitive BE and a random sample of controls without BE were invited to undergo standardised mid-abdomen non-contrast computerised axial tomography images, which were analysed by semiautomated image segmentation software. The effect of VAT and SAT surface areas and their ratio (VAT to SAT) on BE were analysed in logistic regression models. Results A total of 173 BE cases, 343 colonoscopy controls and 172 endoscopy controls underwent study EGD and CT scan. Participants with BE were more than twice as likely to be in the highest tertile of VAT to SAT ratio (OR: 2.42 (1.51 to 3.88) and adjusted OR 1.47 (0.88 to 2.45)) than colonoscopy controls, especially for those long (≥3 cm) segment BE (3.42 (1.67 to 7.01) and adjusted OR 1.93 (0.92 to 4.09)) and for white men (adjusted OR 2.12 (1.15 to 3.90)). Adjustment for gastroesophageal reflux disease (GERD) symptoms and proton pump inhibitors (PPI) use attenuated this association, but there was a significant increase in BE risk even in the absence of GERD or PPI use. Conclusions Large amount of visceral abdominal fat relative to subcutaneous fat is associated with a significant increase in the risk of BE. GERD may mediate some but not all of this association.

Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study.

Eosinophil and mast cell counts were done in 44 patients with active ulcerative colitis, 10 patients with ulcerative colitis in remission, and 44 matched subjects with functional bowel disorder. Mean (±sd) rectal eosinophil counts (EC) per unit area were significantly high (P<0.01) in active ulcerative colitis (5.80±5.49) as compared with inactive disease (2.81±2.19) or controls (3.01±1.67). Eosinophil count was not significantly different in the acute stage between responder (6.36±5.95) and nonresponders (5.1±5.84) to medical treatment and was thus of little discriminatory and prognostic value. Mean (±sd) EC was reduced from 6.36±5.95 to 3.91±3.19 in responders after four weeks of medical treatment. There was little change in the EC with treatment in nonresponders. No correlation was seen between tissue eosinophils and clinical severity of ulcerative colitis. Mast cell count was not significantly different between patients with active ulcerative colitis, inactive disease, and controls and thus had little diagnostic or prognostic value. It can be concluded therefore, that EC in the rectal mucosa indicated activity but not severity of ulcerative colitis. A reduction in EC possibly indicated remission. Rectal EC, however, cannot correctly prognosticate the treatment response and outcome of the disease.

Intravariceal versus paravariceal sclerotherapy: a prospective, controlled, randomised trial.

Fifty four consecutive patients with oesophageal variceal bleeding were randomised to undergo intravariceal (28 patients) or paravariceal (26 patients) sclerotherapy, every three weeks. Intravariceal technique was found significantly (p less than 0.01) more effective in controlling active variceal bleeding than the paravariceal technique (91% v 18.7% respectively). The mean (+/- SD) time taken for variceal eradication by intravariceal sclerotherapy (15.4 +/- 5.3 weeks) was significantly (p less than 0.001) less than paravariceal (26.8 +/- 6.6 weeks) technique. The number of sclerotherapy sessions needed with intravariceal technique were also significantly less. Rebleeding was seen in 38.5% patients after para and 14.3% after intravariceal injections (NS). Except for retrosternal pain, which occurred more often (p less than 0.01) with paravariceal technique, there was no difference in the incidence of other complications or mortality between the two groups. Variceal recurrence was seen in seven patients (25%) in the intra and one (3.9%) patient in the paravariceal group (p less than 0.01) after a mean follow up of 29.4 +/- 9.1 weeks. Intravariceal sclerotherapy was superior to paravariceal in the control of active variceal bleeding and for total variceal obliteration, but was associated with a higher variceal recurrence.

Pancreaticobiliary ductal union in biliary diseases. An endoscopic retrograde cholangiopancreatographic study.

To assess whether the anatomy of the pancreaticobiliary ductal drainage into the duodenum has any relationship with biliary diseases we analyzed 259 endoscopic retrograde cholangiopancreatograms. These included 102 normal examinations (control group), 95 patients with gallstone disease, and 21 patients with carcinoma of the gallbladder. In the control group, 64 (63%) subjects had a common channel and 38 (37%) had separated openings for the common bile duct and the main pancreatic duct. By contrast, the prevalence rate of a common channel was significantly lower in gallstone disease [28 (30%); p less than 0.001]. No such difference, compared with controls, was observed in patients with carcinoma of the gallbladder. The length of the common channel in the control group (mean +/- SD, 4.7 +/- 2.5 mm) was similar to that in gallstone disease (4.6 +/- 2.6 mm). However, patients with carcinoma of the gallbladder had a significantly longer common channel (8.3 +/- 4 mm; p less than 0.001) compared with the control group. An abnormally long common channel (greater than or equal to 8 mm) was seen more frequently in carcinoma of the gallbladder (8 of 21; 38%) compared with normal subjects (3 of 102; 3%) and patients with gallstones (1 of 95; 1%); the difference was highly significant (p less than 0.001 for each). These observations suggest a close association between the anatomy of the distal ends of the common bile duct and main pancreatic duct and the development of gallstones and carcinoma of the gallbladder.