Estimating the cost-effectiveness of detecting cases of chronic hepatitis C infection on reception into prison

Background In England and Wales where less than 1% of the population are Injecting drug users (IDUs), 97% of HCV reports are attributed to injecting drug use. As over 60% of the IDU population will have been imprisoned by the age of 30 years, prison may provide a good location in which to offer HCV screening and treatment. The aim of this work is to examine the cost effectiveness of a number of alternative HCV case-finding strategies on prison reception Methods A decision analysis model embedded in a model of the flow of IDUs through prison was used to estimate the cost effectiveness of a number of alternative case-finding strategies. The model estimates the average cost of identifying a new case of HCV from the perspective of the health care provider and how these estimates may evolve over time. Results The results suggest that administering verbal screening for a past positive HCV test and for ever having engaged in illicit drug use prior to the administering of ELISA and PCR tests can have a significant impact on the cost effectiveness of HCV case-finding strategies on prison reception; the discounted cost in 2017 being £2,102 per new HCV case detected compared to £3,107 when no verbal screening is employed. Conclusion The work here demonstrates the importance of targeting those individuals that have ever engaged in illicit drug use for HCV testing in prisons, these individuals can then be targeted for future intervention measures such as treatment or monitored to prevent future transmission

A framework for crosslinguistic nonword repetition tests: Effects of bilingualism and socioeconomic status on children’s performance

Purpose: As a recognised indicator of language impairment, nonword repetition has unique potential for distinguishing language impairment from difficulties due to limited experience and knowledge of a language. This study focused on a new Crosslinguistic Nonword Repetition framework (CL-NWR) comprising three tests that vary the phonological characteristics of nonwords in the quest for an assessment that minimises effects of language experience and knowledge, and thereby maximises potential for assessing children with diverse linguistic experience. Method: The English version of the CL-NWR was administered, with a test of receptive vocabulary, to 4-7-year-old typically developing monolingual and bilingual children (n=21 per group) from mid-high and low socioeconomic (SES) neighbourhoods. Results: Receptive vocabulary was affected by both bilingualism and neighbourhood SES. In contrast, no effects of bilingualism or neighbourhood SES were found on two of our nonword repetition tests, while the most language-specific test yielded a borderline effect of neighbourhood SES but no effect of bilingualism. Conclusions: Findings support the potential of the CL-NWR tests for assessing children regardless of lingual/socioeconomic background. They also highlight the importance of considering the characteristics of nonword targets, and investigating the compound influence of bilingualism and SES on different language assessments

Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon

Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. Conclusion: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis. (H EPATOLOGY 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83750/1/24169_ftp.pd

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland

We investigated trends in first time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991 2006. We identified new cases of HCC through record linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI):0.9 11.6%, P¼0.021). The adjusted relative risk of HCC was greater for males (hazard ratio¼2.7, 95% CI: 1.7 4.2), for those aged 60 years or older (hazard ratio ¼2.7, 95% CI: 1.9 4.1) compared with 50 59 years, and for those with a previous alcohol related hospital admission (hazard ratio¼2.5, 95% CI: 1.7 3.7). The risk of individuals diagnosed with HCV developing HCC was greatlyincreased compared with the general Scottish population (standardised incidence ratio¼127, 95% CI: 102 156). Owing to the advancing age of the Scottish HCV diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system

Liver injury from herbals and dietary supplements in the U.S. Drug‐Induced Liver Injury Network

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108649/1/hep27317.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108649/2/hep27317-sup-0001-supptbl1.pd

HCV Infection among Saudi Population: High Prevalence of Genotype 4 and Increased Viral Clearance Rate

HCV is a major etiological agent of liver disease with a high rate of chronic evolution. The virus possesses 6 genotypes with many subtypes. The rate of spontaneous clearance among HCV infected individuals denotes a genetic determinant factor. The current study was designed in order to estimate the rate of HCV infection and ratio of virus clearance among a group of infected patients in Saudi Arabia from 2008 to 2011. It was additionally designed to determine the genotypes of the HCV in persistently infected patients. HCV seroprevalence was conducted on a total of 15,323 individuals. Seropositive individuals were tested by Cobas AmpliPrep/Cobas TaqMan HCV assay to determine the ratio of persistently infected patients to those who showed spontaneous viral clearance. HCV genotyping on random samples from persistently infected patients were conducted based on the differences in the 5′untranslated region (5′UTR). Anti-HCV antibodies were detected in 7.3% of the totally examined sera. A high percentage of the HCV infected individuals experienced virus clearance (48.4%). HCV genotyping revealed the presence of genotypes 1 and 4, the latter represented 97.6% of the tested strains. Evidences of the widespread of the HCV genotype 4 and a high rate of HCV virus clearance were found in Saudi Arabia

Viral Hepatitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65791/1/j.1365-4362.1981.tb00836.x.pd

Zinc-induced Dnmt1 expression involves antagonism between MTF-1 and nuclear receptor SHP

Dnmt1 is frequently overexpressed in cancers, which contributes significantly to cancer-associated epigenetic silencing of tumor suppressor genes. However, the mechanism of Dnmt1 overexpression remains elusive. Herein, we elucidate a pathway through which nuclear receptor SHP inhibits zinc-dependent induction of Dnmt1 by antagonizing metal-responsive transcription factor-1 (MTF-1). Zinc treatment induces Dnmt1 transcription by increasing the occupancy of MTF-1 on the Dnmt1 promoter while decreasing SHP expression. SHP in turn represses MTF-1 expression and abolishes zinc-mediated changes in the chromatin configuration of the Dnmt1 promoter. Dnmt1 expression is increased in SHP-knockout (sko) mice but decreased in SHP-transgenic (stg) mice. In human hepatocellular carcinoma (HCC), increased DNMT1 expression is negatively correlated with SHP levels. Our study provides a molecular explanation for increased Dnmt1 expression in HCC and highlights SHP as a potential therapeutic target

Outcomes in hepatitis C virus–infected recipients of living donor vs. deceased donor liver transplantation

In this retrospective study of hepatitis C virus (HCV)–infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT ( P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients ( P 20 and DDLT were not significantly different ( P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation. Liver Transpl 13:122–129, 2007. © 2006 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55915/1/20995_ftp.pd