Search

Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.Results: A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.Conclusions: As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The estimated association between Helicobacter pylori and Barrett's esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association.METHODS:We conducted a case-control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders.RESULTS:We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35-0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63).CONCLUSIONS:The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week). [ABSTRACT FROM AUTHOR]

OBJECTIVES:Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis.METHODS:Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire.RESULTS:Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P=0.06).CONCLUSIONS:We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known. [ABSTRACT FROM AUTHOR]

Background: Pegylated interferon (PEGIFN) and ribavirin combination is the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naïve HCV-infected patients have shown conflicting results. Aim: We performed a systematic review and meta-analysis of studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in HCV-infected patients naïve to treatment. Methods: Nine studies (five abstracts) with 3,546 patients (1,771 treated with PEGIFN alfa-2a) comparing PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naïve HCV patients were analyzed. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects (SAE). Results: Pooled data on outcomes (reported as odds ratios [ORs] with 95% confidence intervals [CIs]: [OR (95% CI)]) showed higher SVR in patients treated with PEGIFN alfa-2a as compared to treatment with PEGIFN alfa-2b [1.36 (1.07-1.73); P = 0.01]. Subgroup analysis of good quality studies on SVR in genotypes 2 and 3 also favored PEGIFN alfa-2a over PEGIFN alfa-2b (1.91 [1.09-3.37]; P = 0.02). SVR results obtained with the two types of IFN showed no impact of viral load and the presence or absence of cirrhosis. Treatment discontinuation rates due to SAE, reported in six studies (two abstracts) on 3,211 patients (1,604 treated with PEGIFN alfa-2a), were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Conclusions: PEGIFN alfa-2a has superior efficacy with higher SVR as compared to PEGIFN alfa-2b in treatment-naïve HCV-infected patients. The safety profile of the two types of PEGIFN was similar. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. (Am J Gastroenterol 2005;100:1–8) [ABSTRACT FROM AUTHOR]

Acute pancreatitis is a rare complication of interferon (IFN) and ribavirin (RBV) therapy. The aim of this study was to determine the incidence, clinical presentation, and outcome of acute pancreatitis in patients with chronic hepatitis C virus (HCV) infection treated with IFN and RBV combination therapy. We conducted a retrospective review of 1706 HCV-infected patients treated with IFN alpha-2b and RBV. The diagnosis of drug-induced acute pancreatitis was made based on the presence of epigastric pain, elevated amylase and lipase levels, and the absence of other identifiable causes of pancreatitis. Acute pancreatitis was diagnosed in 7 of 1706 HCV-infected patients (0.4%; 95% CI, 0.2 to 0.8%) who were treated with IFN alpha-2b and RBV. The mean age of the patients (four males and three females) was 51.4 +/- 4.7 years and the median duration of therapy prior to development of pancreatitis was 12.0 weeks (range, 4.0-21.0 weeks). All patients presented with epigastric pain associated with nausea, vomiting, and/or fever. The median amylase and lipase values at the time of diagnosis of pancreatitis were 330.0 U/L (range, 182.0-1813.0 U/L) and 500.0 U/L (range, 171.0-2778.0 U/L), respectively. IFN and RBV were discontinued in all patients at the time of diagnosis and six of the seven patients were hospitalized; one patient refused hospital admission. Pancreatitis resolved in all seven patients and none of these individuals had recurrent pancreatitis during a median follow-up of 18.0 months (range, 3.0-27.0 months). In conclusion, IFN and RBV combination therapy is a potential cause of drug-induced pancreatitis in patients with chronic HCV. In these individuals, pancreatitis is often severe enough to warrant hospital admission, although symptoms resolve promptly after discontinuation of antiviral therapy. [ABSTRACT FROM AUTHOR]

: ObjectiveHepatitis 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.: MethodsWe 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.: ResultsWe 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.: ConclusionsSeveral 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. [Copyright &y& Elsevier]

Chronic alcoholics have a high prevalence of hepatitis C virus (HCV) infection. The present study was carried out to examine the association between HCV infection and alcohol abuse, and the influence of these factors on the severity of liver disease. Patients with history of heavy alcohol abuse (> or = 80 g of ethanol per day for > or = 5 years) were analyzed with respect to the amount of alcohol use, clinical evidence of liver disease, and laboratory tests. One hundred ninety-nine patients, 137 HCV positive and 62 HCV negative were included in the study. HCV-infected subjects had liver disease for a longer duration (P < 0.0001) and had higher incidence of symptoms of hepatic decompensation in the past compared to uninfected alcoholics. Several differences were noted between the two groups at the time of presentation to the hospital. Alcoholics with HCV infection had lower daily alcohol consumption (P < 0.001), were abstinent for a longer duration (P < 0.02) and had lower lifetime use of ethanol (P < 0.005) compared to HCV-negative subjects. Assessment of liver tests showed greater derangement in uninfected alcoholics compared to HCV-positive subjects. The present study shows that HCV-infected chronic alcoholics have lower alcohol consumption and, perhaps as a consequence, have less severe liver disease compared to HCV-negative individuals. These findings suggest that in chronic alcoholics, despite the presence of HCV infection, the severity of liver damage is related to the amount of alcohol consumption. [ABSTRACT FROM AUTHOR]

Examines the effect of phosphatidylcholine (PC)-associated aspirin (ASA) on the gastric mucosa. Reduction of acute aspirin-induced damage to the gastric mucosa by chemically associating ASA with PC; Lack of relation of the mechanism of mucosal protection provided by the compound to any alteration in the ability of ASA to inhibit mucosal cyclooxygenase activity; Attribution of protection to the maintenance of the defensive hydrophobic barrier of the gastric mucosa.

Varicella (chicken pox) is a common viral infection in children and generally runs a benign course. However, in adults, and especially in immunocompromised subjects such as those on immunosuppressant therapy or with AIDS, varicella infection is particularly severe and is associated with the formation of hemorrhagic skin lesions and visceral involvement. These patients are at an increased risk of developing varicella hepatitis, which frequently results in fulminant hepatic failure and death. In the present report, we describe for the first time the course of disease and the histological appearance of varicella hepatitis in a patient infected with the human T cell lymphotropic viruses (HTLV) I and II; these viruses have many characteristics in common with the human immunodeficiency virus (HIV). Our patient had a relatively benign illness, suggesting that varicella infection in the presence of HTL VI and II may not run as severe a course as it does in patients with HIV infection. [ABSTRACT FROM AUTHOR]

Most patients with carcinoma of the esophagus have advanced disease at presentation. Since cure is usually not possible, the goal of treatment is the palliation of dysphagia. Palliative modalities include bougies, balloons, stents, tumor probe, laser, surgery, chemotherapy, and radiation. In recent years, combined chemotherapy and radiation has shown promising results. However, the relief of dysphagia is slow and frequently incomplete. We compared the effectiveness of dilatation alone versus dilatation plus Nd-YAG laser therapy for the relief of dysphagia while assessing the role of chemotherapy and radiation as an adjunct to surgery. Fifteen patients with squamous cell carcinoma of esophagus who were deemed fit for intensive chemotherapy and radiation were randomized to receive either dilatation alone (N = 7) or dilatation plus laser (N = 8); the end-point for initial success was the passage of a 45 French Savary dilator, and the relief of dysphagia. At entry, 13 of these 15 patients were judged potentially resectable. However, after chemotherapy and radiation, only 3 of 13 (20%) patients could be offered surgery; the remainder were considered too poor a surgical risk. Follow-up was for 30 months, or until death. Further dilatations were performed as needed for relief of dysphagia. No difference was observed between the laser plus dilatation and the dilatation alone group with respect to the degree of dysphagia, weight record, quality of life index (Karnofsky score), or mortality rate. Our results indicate that in patients undergoing chemotherapy and radiation for esophageal carcinoma, dilatation alone provides adequate palliation of dysphagia, and in these patients, chemotherapy and radiation is a poor adjunct to surgical treatment. [ABSTRACT FROM AUTHOR]

Background: Infestation with Ascaris lumbricoides is seen worldwide. Recently, there has been much interest in the pancreatic-biliary complications of Ascaris infection. In this study, we present our experience of 300 patients seen in a tertiary referral center. Materials and Methods: Case charts of patients seen in the Department of Gastroenterology, University of Damascus, Syria, were analyzed, retrospectively, over a 5-yr period (September of 1988 to August of 1993). During this period, 1666 endoscopic retrograde cholangiopancreatographic studies were performed and pancreatic-biliary ascariasis was diagnosed in 300 patients (18%). Results: The most common presenting symptom was abdominal pain, seen in 98% of patients (294 patients). Complications observed were ascending cholangitis (48 patients; 16%), acute pancreatitis (13 patients; 4.3%), and obstructive jaundice (4 patients; 1.3%). History of worm emesis was present in 25% of patients (76 patients). Most patients (240 patients; 80%) had previously undergone a cholecystectomy or an endoscopic sphincterotomy (232 patients; 77%). Worms were successfully extracted endoscopically in all except two patients, and there were no procedure-related complications. Conclusions: in endemic countries, ascariasis should be suspected in patients with pancreatic-biliary disease, especially if a cholecystectomy or sphincterotomy has been performed in the past. Endoscopic management results in rapid resolution of symptoms and prevents development of complications. [ABSTRACT FROM AUTHOR]

The inhibitory effect of different drugs on pancreatic secretions was assessed in a patient with a posttraumatic pancreatic-cutaneous fistula. The various drugs examined were: pancreatic enzymes, competition, verapamil, propantheline, acetazolamide, and somatostatin analog octreotide. Only fasting and octreotide reduced pancreatic secretion. The optimum dose of octreotide was 50 μg bid given subcutaneously; increasing the dose up to 100 μg tid had no additional benefit. A stable pancreatic-cutaneous fistula is an excellent model to assess the effect of different therapeutic measures on pancreatic secretion. [ABSTRACT FROM AUTHOR]