Diagnosis of hepatitis C

Currently, the second- and third-generation enzyme immunoassays (EIA-2 and EIA-3) for hepatitis C virus antibody (anti-HCV) are the most practical screening tests for the diagnosis of HCV infection. The need for and the choice of supplementary or confirmatory tests depend on the clinical setting and the likelihood of a true-positive EIA result. Detection of HCV RNA in serum by polymerase chain reaction (PCR) assay is the gold standard for the diagnosis of HCV infection. However, the lack of uniformity in current PCR assays has tarnished this standard. Confirmatory tests for the diagnosis of HCV infection are in general unnecessary in anti-HCV-positive patients who present with chronic liver disease. When indicated, the most appropriate test in this setting is a qualitative PCR assay for HCV RNA. Confirmatory tests should always be performed in anti-HCV-positive blood donors and individuals with normal aminotransferase levels. The most appropriate approach is to retest for anti-HCV using recombinant immunoblot assay (RIBA) and then test for HCV RNA using PCR assay in those who are RIBA positive or indeterminate. Liver histology is the gold standard in assessing severity of liver disease. Quantitative tests for serum HCV RNA levels do not help to determine the severity of liver disease. At the moment, HCV genotyping should be considered a research tool and not a part of the diagnostic work-up in clinical practice. The goals of treatment for chronic hepatitis C are sustained biochemical and virological response. Viral clearance should be determined by qualitative PCR assay. Quantifying serum HCV RNA level can help in predicting response to interferon treatment, but further studies using more standardized assays are needed to determine if these values can be used to select patients for treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34770/1/510260709_ftp.pd

Unsuspected infection is infrequent in asymptomatic outpatients with refractory ascites undergoing therapeutic paracentesis

Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites. However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis. The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis. Methods : Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%). After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects. Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed. The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed. Results : All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm 3 (mean = 6.5 ± 22.5 pmn/mm 3 ). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings. Conclusion : Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection. In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73079/1/j.1572-0241.1999.01445.x.pd

A randomized, controlled trial to assess a novel colorectal cancer screening strategy: the conversion strategy

Our study was a randomized, controlled trial to assess a novel strategy that provides comprehensive colorectal cancer screening in a single visit versus traditional sigmoidoscopy and, where appropriate, colonoscopy on a subsequent day. METHODS : Consecutive patients referred for screening were randomized to control or so-called “conversion” groups. Patients in the control group were prepared for sigmoidoscopy with oral phospho-soda. Those with an abnormal sigmoidoscopy were scheduled for colonoscopy on a future day after oral polyethylene glycol preparation. In the conversion group, patients were prepared with oral phospho-soda. Patients with a polyp >5 mm or multiple diminutive polyps were converted from sigmoidoscopy to colonoscopy, allowing comprehensive screening in a single visit. Clinical outcomes were assessed by postprocedure physician and patient questionnaires. RESULTS : Two hundred thirty-five patients were randomized (control = 121, conversion = 114). In the control group, 28% had an indication for colonoscopy. Three of 33 (9%) with an abnormal sigmoidoscopy did not return for colonoscopy. At colonoscopy, 27% had a proximal adenoma. In the conversion group, 28% had an abnormal sigmoidoscopy and underwent conversion to colonoscopy. Forty-one percent undergoing colonoscopy in the conversion group had a proximal adenoma. Physicians reported no differences in preparation or procedure difficulty, whereas patients reported no differences in the level of comfort or overall satisfaction between groups. When queried regarding preferences for future screening, 96% chose the conversion strategy. CONCLUSIONS : The conversion strategy led to similar outcomes compared to traditional screening while improving compliance with colonoscopy in patients with an abnormal sigmoidoscopy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73097/1/j.1572-0241.2000.02231.x.pd

A new model for diabetes-focused capacity building – lessons from Sri Lanka

Abstract Sri Lanka is experiencing a rapid increase in the number of people with diabetes mellitus (DM) due to population growth and aging. Physician shortages, outdated technology, and insufficient health education have contributed to the difficulties associated with managing the burden of disease. New models of chronic disease management are needed to address the increasing prevalence of DM. Medical students, business students, and faculty members from the University of Michigan partnered with the Grace Girls’ Home, Trincomalee General Hospital, and Selvanayakapuram Central Hospital to identify and train diabetes-focused medical assistants (MAs) to collect and enter patient data and educate patients about their disease. Return visits to these MAs were encouraged so that patient progress and disease progression could be tracked longitudinally. Data entry was conducted through a cloud-based mechanism, facilitating patient management and descriptive characterization of the population. We implemented this pilot program in June 2016 in coordination with Trincomalee General Hospital and Selvanayakapuram Central Hospital. Over a 12-month period, 93 patients were systematically assessed by the medical assistants. All patients received education and were provided materials after the visit to better inform them about the importance of controlling their disease. Fifteen percent (14/93) of patients returned for follow-up consultation. Trained MAs have the potential to provide support to physicians working in congested health systems in low-resource settings. Public investment in training programs for MAs and greater acceptance by physicians and patients will be essential for handling the growing burden associated with chronic illnesses like DM. Trained MAs may also play a role in improved patient education and awareness regarding diabetes self-management.https://deepblue.lib.umich.edu/bitstream/2027.42/146742/1/40842_2018_Article_74.pd

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes