Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis.

BACKGROUND: The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct-acting anti-viral (DAA) therapy provides effective treatment for patients with cirrhosis. AIM: To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population. METHODS: A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross-referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir. RESULTS: Successful direct-acting anti-viral treatment is now possible in patients with HCV-related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (SVR) of 90-95%. Overall success rates in GT1 cirrhosis are excellent while GT3-infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT3 cirrhosis achieving SVR of ~90%. CONCLUSIONS: Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard-to-cure groups of GT3 cirrhosis and direct-acting anti-viral failures, and managing drug-drug interactions.

Infection with wild-type mumps virus in army recruits temporally associated with MMR vaccine.

Four cases of mumps were reported among 180 army recruits who had received MMR vaccine 16 days earlier. Mumps serology, salivary mumps IgM and PCR tests for the SH gene were performed on the 4 cases and on 5 control recruits who remained well. PCR products were sequenced and the sequences compared to those of wild type and vaccine strains of mumps. Further salivary mumps IgM tests were performed on the remaining 171 recruits. Mumps infection was confirmed in the 4 cases but not in the 5 controls. The controls had serological evidence of prior immunity. The SH gene sequence found in the 4 cases was wild type. Saliva tests identified 2 additional recruits with mumps IgM, one of whom had presented with suspected mumps 2 days before the MMR vaccine was given. Thus 6 (5 symptomatic and 1 asymptomatic) cases of mumps in army recruits recently receiving MMR vaccine were not due to the vaccine but to coincidental infection with wild-type mumps virus. The probable index case was revealed by salivary mumps IgM tests. This study highlights the importance of appropriate investigation of illness associated with MMR vaccination.

The requirement for hepatitis A vaccine in Gurkha soldiers.

This Hepatitis A seroprevalence study aimed to determine the cost effectiveness of Hepatitis A vaccination for Gurkha soldiers. One hundred and sixty Gurkha recruits had serum analysed for Hepatitis A IgG. One hundred and fifty nine (99.4%) were IgG positive. Continuing to vaccinate Gurkha soldiers against Hepatitis A will confer little benefit and is not cost effective.

Sentence combining as a technique for increasing adjective use in writing by students with autism.

A multiple-baseline across-subjects design was used to determine whether reinforcement alone or in combination with sentence-combining exercises would increase the number of descriptive adjectives used in daily writing samples by three adolescents with autism. The cumulative number of new adjectives (adjectives never before used by a student in the entire study) was also recorded. Experimental conditions were baseline, sentence combining, and maintenance. Writing sessions consisted of a 20-min worksheet period followed by a 20-min writing period. The addition of sentence-combining exercises increased the number of adjectives in the students' writing samples. Maintenance of this increase occurred in the absence of sentence-combining lessons and in the presence of reinforcement for use of adjectives. The addition of sentence-combining exercises also increased the cumulative number of new adjectives, although new adjectives did not occasion reinforcement, and we had not expected their use to increase in students with autism without specific instruction. Maintenance of new adjective use also was demonstrated. Finally, for all three students, minimal terminable unit (T-unit) length, a measure that facilitates comparison with normative data, increased from baseline to maintenance, and independent raters judged writing samples written during maintenance as better than those written during baseline.