Rate,delay and predictors of hepatitis C treatment in British Columbia

BACKGROUND:

The current treatment rate for chronic hepatitis C virus (HCV) infection is suboptimal despite the availability of efficacious antiviral therapy.

OBJECTIVE:

To determine the rate, delay and predictors of treatment in patients with chronic HCV infection.

METHODS:

A retrospective chart review of chronic HCV patients who were being evaluated at a tertiary hepatology centre in Vancouver, British Columbia, was performed.

RESULTS:

One hundred sixty-four patients with chronic HCV infection who were assessed for treatment between February 2008 and January 2013 were reviewed. Treatment was initiated in 25.6% (42 of 164). In multivariate analyses, male sex (OR 7.90 [95% CI 1.35 to 46.15]) and elevated alanine aminotransferase (ALT) level (>1.5 times the upper limit of normal) (OR 3.10 [95% CI 1.32 to 7.27]) were positive predictors of treatment, whereas active smoking (OR 0.09 [95% CI 0.02 to 0.53]) and Charlson comorbidity index (per point increase) (OR 0.47 [95% CI 0.27 to 0.83]) were negative predictors of treatment. The most common reasons for treatment deferral were no or minimal liver fibrosis in 57.7% (n=30), persistently normal ALT levels in 57.7% (n=30) and patient unreadiness in 28.8% (n=15). The most common reasons for treatment noninitiation were patient refusal in 59.1% (n=26), medical comorbidities in 36.4% (n=16), psychiatric comorbidities in 9.1% (n=4) and decompensated cirrhosis in 9.1% (n=4). There was a statistically significant difference in the median time delay from HCV diagnosis to general practitioner referral between the treated and untreated patients (66.3 versus 119.5 months, respectively [P=0.033]). The median wait time from general practitioner referral to hepatologist consult was similar between the treated and untreated patients (1.7 months versus 1.5 months, respectively [P=0.768]). Among the treated patients, the median time delay was 6.8 months from hepatologist consult to treatment initiation.

CONCLUSIONS:

The current treatment rate for chronic HCV infection remains suboptimal. Medical and psychiatric comorbidities represent a major obstacle to HCV treatment. Minimal hepatic fibrosis may no longer be a major reason for treatment deferral as more efficacious and tolerable antiviral therapies become available in the future. Greater educational initiatives for primary care physicians would promote early referral of patients. More nursing support would alleviate the backlog of patients awaiting treatment.     

Seroprevalences of hepatitis B virus and hepatitis C virus among participants of an Asian health fair in the Lower Mainland,British Columbia

BACKGROUND:

The seroprevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) are 0.4% and 0.8%, respectively, in Canada, but varying rates have been reported in different populations.

OBJECTIVES:

To determine the seroprevalences of HBV and HCV among attendees of an Asian health fair in the Lower Mainland, British Columbia, as well as to correlate questionnaire answers regarding vaccination status to serological profiles.

METHODS:

Attendees at an Asian health fair were invited to participate in the present study on a voluntary basis. They provided answers to a questionnaire including ethnicity and vaccination status. Blood was then drawn for HBV and HCV serology. Active HBV was defined as HBV surface antigen (HBsAg) positive while HCV seroprevalence was defined as HCV antibody reactive. Previous exposure to HBV was defined as HBV core antibody (anti-HBc) positive and HBsAg negative. Nonimmunity was defined as anti-HBc negative and HBV surface antibody negative. Only those with correct demographic information matched to serological results were included in the study.

RESULTS:

There were 192 consenting attendees of the fair, of whom 112 were included in the study. Of the participants, 91% were Chinese. Active HBV infection was found in three participants (2.7% [95% CI 0.6% to 7.6%]) and HCV infection was found in two participants (1.8% [95% CI 0.2% to 6.3%]). More than 40% of participants had been previously exposed to HBV (42% [95% CI 33% to 51%]). Almost 20% demonstrated nonimmunity to HBV (19% [95% CI 12% to 27%]). There was significant discordance when questionnaire answers regarding vaccination status were compared with serological profiles.

CONCLUSION:

The seroprevalences of HBV and HCV in this cohort were 2.7% and 1.8%, respectively – higher than nationally reported rates. Our results highlight that the lack of knowledge of HBV infection and vaccination status remains a significant clinical issue in the Asian community of British Columbia.     

Physicians' attitudes and practice toward treating injection drug users with hepatitis C: results from a national specialist survey in Canada

BACKGROUND:

In Canada, more than 70% of new cases of hepatitis C virus (HCV) infection per year involve injection drug users (IDUs) and, currently, there is no consensus on how to offer them medical care.

OBJECTIVE:

To examine the characteristics of Canadian specialist physicians and their likelihood to provide treatment to HCV patients who are IDUs.

METHODS:

A nationwide, cross-sectional study was conducted in the specialty areas of hepatology, gastroenterology and infectious diseases to examine HCV services. The questionnaire requested information regarding basic demographics, referral pathways and opinions (yes/no), and examined how a physician’s treatment regimen is influenced by factors such as treatment eligibility, HCV care management and barriers to providing quality service.

RESULTS:

Despite the fact that the majority of prevalent and incident cases of HCV are associated with injection drug use, very few specialist physicians actually provide the necessary therapy to this population. Only 19 (19.79%) comprehensive service providers were likely to provide treatment to a current IDU who uses a needle exchange on a regular basis. The majority of comprehensive service providers (n=86 [89.58%]) were likely to provide treatment to a former IDU who was stable on substitution therapy. On bivariate analysis, factors associated with the likelihood to provide treatment to current IDUs included physicians’ type, ie, infectious disease specialists compared with noninfectious specialists (OR 3.27 [95% CI 1.11 to 9.63]), and the size of the community where they practice (OR 4.16 [95% CI 1.36 to 12.71] [population 500,000 or greater versus less than 500,000]). Results of the multivariate logistic regression analysis were largely consistent with the results observed in the bivariate analyses. After controlling for other confounding variables, only community size was significantly associated with providing treatment to current IDUs (OR 3.89 [95% CI 1.06 to 14.26] [population 500,000 or greater versus less than 500,000]).

CONCLUSION:

The present study highlighted the reluctance of specialists to provide treatment to current IDUs infected with HCV. Providing treatment services for HCV-infected substance abusers is challenging and there are many treatment barriers. However, effective delivery of treatment to this population will help to limit the spread of HCV. The present study clearly identified a need for improved HCV treatment accessibility for IDUs.     

Improving access to care by allowing self-referral to a hepatitis C clinic

BACKGROUND

Estimates suggest that more than 250,000 Canadians are infected with hepatitis C virus (HCV), but less than 10% have been treated. Access to specialists in Canada is usually via health care professional (HCP) referral and, therefore, may be a barrier to HCV care. However, clinics that operate in conjunction with the Hepatitis Support Program, Edmonton, Alberta, allow self-referral. It is hypothesized that this improves access to care without increasing inappropriate referrals.

OBJECTIVE

To compare the baseline characteristcs and outcomes of HCV patients who self-referred with those who were HCP-referred.

METHODS

Data were collected from the Hepatitis Support Program HCV database and chart reviews.

RESULTS

Between December 17, 2002, and December 31, 2007, 1563 patients were referred including 336 self- (21.5%) and 1227 HCP- referrals (78.5%). Self- and HCP-referred patients were similar in terms of age (mean [± SD] 43.0±10.3 years versus 43.9±10.0 years, respectively; P=0.18), sex (56.8% versus 62.0% [men], respectively; P=0.08) and risk factors for HCV (P=0.3), with 49.7% and 52.6%, respectively, identifying injection drug use as the primary risk factor. The two groups had similar HCV genotype distributions and liver biopsy fibrosis scores with similar treatment rates (31.3% versus 33.2%; P=0.6). Treatment outcomes were excellent (sustained virological response 40.2% for genotype 1, 67% for genotypes 2 and 3) in patients completing therapy and were similar between the two groups.

CONCLUSION

Self-referred patients comprised 21.5% of patients accessing care in the clinic. Self- and HCP-referred patients had similar characteristics, treatment rates and outcomes. Facilitating self- referral to an HCV clinic can improve access to care, including risk reduction education and HCV treatment.     

Antidepressant prophylaxis reduces depression risk but does not improve sustained virological response in hepatitis C patients receiving interferon without depression at baseline: A systematic review and meta-analysis

BACKGROUND:

Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a full course of therapy. As a consequence, the likelihood of achieving a sustained virological response (SVR [ie, permanent viral eradication]) is reduced.

OBJECTIVE:

To systematically review the evidence of whether preemptive antidepressant prophylaxis started before HCV antiviral initiation is beneficial.

METHODS:

Inclusion was restricted to randomized controlled trials in which prophylactic antidepressant therapy was started at least two weeks before the initiation of HCV antiviral treatment. Studies pertaining to patients with active or recent depressive symptoms before commencing HCV antiviral therapy were excluded. English language articles from 1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central databases were searched. Where possible, meta-analyses were conducted evaluating the effect of antidepressant prophylaxis on SVR and major depression as well as on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias risk.

RESULTS:

Six randomized clinical trials involving 522 patients met the inclusion criteria. Although the frequency of on-treatment clinical depression was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to 0.93]; P=0.02; I²=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI 0.74 to 1.57]; P=0.69; I²=58%).

CONCLUSION:

This practice is not justified to improve SVR in populations free of active depressive symptoms leading up to HCV antiviral therapy.     

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort

BACKGROUND:

Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM).

OBJECTIVE:

To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use.

METHODS:

Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY).

RESULTS:

In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load.

CONCLUSIONS:

These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.     

Hepatitis B and hepatitis C viral infections in patients with chronic lymphocytic leukemia

BACKGROUND:

Whether chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections contribute to the pathogenesis and/or course of chronic lymphocytic leukemia is unclear.

OBJECTIVE:

To document the prevalences of HBV and HCV infections in chronic lymphocytic leukemia patients, and to determine whether infected patients experience more aggressive disease than those without infection.

METHODS:

Patient sera were screened for antibodies to HBV core antigen and HCV (anti-HCV) using ELISA; both sera and peripheral blood lymphocytes were further tested (regardless of antibody results) for HBV-DNA and HCV-RNA using real-time polymerase chain reaction. Prognostic markers for chronic lymphocytic leukemia included Rai stage, IgV_H mutational status, β₂-microglobulin levels, Zap-70 and CD38 status.

RESULTS:

Fourteen of 222 (6.3%) chronic lymphocytic leukemia patients and two of 72 (2.8%) healthy controls tested positive for previous or ongoing HBV infection (OR 2.4 [95% CI 0.5 to 7.7]; P=0.25) while four of 222 (1.8%) chronic lymphocytic leukemia patients and one of 72 (1.4%) controls tested positive for HCV markers (OR 1.3 [95% CI 0.2 to 6.4]; P=0.81). The levels and distribution of the various indicators of aggressive chronic lymphocytic leukemia disease were similar among HBV- and HCV-infected and uninfected patients. Survival times were also similar. Occult HBV and HCV infection (HBV-DNA or HCV-RNA positive in the absence of diagnostic serological markers) were uncommon in chronic lymphocytic leukemia patients (0.5% and 1.8%, respectively).

CONCLUSIONS:

The results of the present study do not support the hypothesis that HBV or HCV infections play an important role in the pathogenesis or course of chronic lymphocytic leukemia.     

Comparing outcomes of donation after cardiac death versus donation after brain death in liver transplant recipients with hepatitis C: A systematic review and meta-analysis

BACKGROUND:

Liver transplantation (LT) using organs donated after cardiac death (DCD) is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV) infection remains unclear due to the limited experience and number of publications addressing this issue.

OBJECTIVE:

To evaluate the clinical outcomes of DCD versus donation after brain death (DBD) in HCV-positive patients undergoing LT.

METHODS:

Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature.

RESULTS:

The search identified 58 citations, including three studies, with 324 patients meeting eligibility criteria. The use of DCD livers was associated with a significantly higher risk of primary nonfunction (RR 5.49 [95% CI 1.53 to 19.64]; P=0.009; I²=0%), while not associated with a significantly different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I²=51%), graft survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I²=34%), rate of recurrence of severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I²=84%), retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84]; P=0.25; I²=44%), and biliary complications.

CONCLUSIONS:

While the literature and quality of studies assessing DCD versus DBD grafts are limited, there was significantly more primary nonfunction and a trend toward decreased graft survival, but no significant difference in biliary complications or recipient mortality rates between DCD and DBD LT in patients with HCV infection. There is insufficient literature on the topic to draw any definitive conclusions.     

Risk Factors for Hepatitis C Virus (HCV) Infection in Areas with a High Prevalence of HCV in the Republic of Korea in 2013

Background/Aims

The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas.

Methods

A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Healthy controls were subjects participating in medical checkups. Conditional logistic regression models were used.

Results

A total of 234 matched-case and patient- and healthy-control pairs were analyzed. The significant risk factors for both controls were sharing razors (adjusted odds ratio [aOR], 2.39 and 3.29, respectively) and having more than four lifetime sexual partners (aOR, 2.15 and 6.89, respectively). Contact dockworkers (aOR, 1.91) and tattoos (aOR, 2.20) were significant risk factors for the patient controls. Transfusion (aOR, 5.38), a bloody operation (aOR, 5.02), acupuncture (aOR, 2.08), and piercing (aOR, 5.95) were significant risk factors for the healthy controls. Needle stick injuries and intravenous drug abuse were significant in the univariate analysis.

Conclusions

More education concerning the dangers of sharing razors, tattoos and piercings is required to prevent HCV infection. More attention should be paid to needle stick injuries in hospitals and the community.     

Sexual Transmission of Hepatitis C Virus Between HIV Infected Subjects and Their Main Heterosexual Partners

Background

Overall, 60-70% of the hepatitis c virus (HCV) transmission routes is parenteral, and in 30-40% of the cases is unknown (e.g. sexual route). Knowing these routes in HIV infected dyads is very important due to clinical and methodological reasons.

Objectives

The present study aimed to identify and quantitatively investigate HIV-infected individuals and their main heterosexual partners regarding the risk factors of HCV transmission.

Patients and Methods

One hundred sixty eight of 984 couples were chosen through random generated numbers using a computer program from behavioral consultation center in Shiraz, Iran. We used actor partner independent model (APIM) and multilevel analysis to assess multiple risk factors for HCV, while partitioning the source of risk at the individual and couple levels.

Results

Age of the index samples was 38.71 ± 7 years, and 33.2 ± 6.3 for their main heterosexual partners; the mean duration of sexual relationship for couples was 11.9 (median = 8.5) years. Multivariate analysis showed that actor risk factor of intravenous drug using (IDU) (AOR= 13.03; 95% CI: 3.9- 43.82) and actor cofactors of HIV positivity (AOR = 7.1; 95% CI: 1.37- 36.97), razor sharing (AOR = 4.81; 95% CI: 1.84- 12.55), sex (AOR = 8.83; 95% CI: 3.16- 24.87), and condom use in sexual activity with main partner (AOR = 0.15; 95% CI: 0.02- 0.44) were associated with actor HCV positivity.

Conclusions

Health care providers need to pay special attention to sexual transmission of HCV among HIV-infected individuals, and should recommend control/preventive measures for HCV sexual transmission.     

Mysterious Linkages Between Hepatitis C Virus Genotypes,Interleukin-28B Genotypes and Viral Clearance- A Meta-Analysis

Background:

Recent genome wide association studies (GWAS) have shown important roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28 (IL28B) gene in spontaneous and drug-induced clearance of hepatitis C virus (HCV) in genotype 1 HCV infection.

Objectives:

This meta-analysis was designed to determine the world-wide distribution patterns of IL28B genotypes and alleles, and to find possible linkages between IL28B and HCV genotypes.

Patients and Methods:

Manual and electronic databases were searched. Critical appraisal was performed. According to the results of heterogeneity tests, we used fix/random model for the analysis. The data concerning patients’ ethnicity and HCV genotypes were analyzed by using statistical analysis software.

Results:

A total of 255 articles were found. After article review and quality assessment, 50 studies, including 18662 patients and 1313 healthy subjects, were analyzed. Presence of HCV genotype 3 versus genotype 1 was significantly associated with a higher frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI: 1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV infected patients. Prevalence of rs12979860 TT genotype in the African-American genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)], and significantly different compared to all other ethnicities.

Conclusions:

There were significant linkages between HCV genotypes and IL28B genotypes/alleles. Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a better chance to clear HCV in the acute phase.     

The impact of sirolimus on hepatitis C recurrence after liver transplantation

BACKGROUND

While some immunosuppression strategies may accelerate hepatitis C virus (HCV) recurrence after liver transplantation (LT), the impact of sirolimus (SRL) is not known.

OBJECTIVE

To assess the risk of biopsy-proven HCV recurrence and patient survival using known and suspected risk factors for HCV recurrence as covariates.

METHODS

A retrospective analysis of 141 consecutive patients, including 88 who received de novo SRL therapy, who had undergone a first LT for HCV cirrhosis was conducted. Known and suspected risk factor covariates including transplant era, donor and recipient age, Model for End-stage Liver Disease score, cold ischemia time, immunosuppressive drugs and steroid treatment rejection rates were used in the assessment.

RESULTS

Overall, 72.3% of the cohort developed biopsy-proven HCV recurrence. The incidence of HCV recurrence was not significantly different for patients treated with SRL (75% versus 69.8%; P=0.5). There was no difference found for time to recurrence, nor did mean activity or fibrosis scores differ at the time of initial recurrence. However, on follow-up using serial biopsies in patients with recurrence, the mean activity and fibrosis scores were significantly lower in the SRL group. Donor age and acute rejection episodes were the only factors affecting the HCV recurrence rate (expB 1.02 [95% CI 1.01 to 1.03]); P=0.03; and expB 2.8 [95% CI 1.8 to 4.3]; P<0.01], respectively). SRL treatment did not alter patient survival rates. Among patients treated with SRL-based immunosuppression, higher drug area under the curve levels were associated with a trend to lower disease activity and fibrosis at diagnosis; however, higher SRL levels were associated with shorter recurrence-free survival (P=0.038).

CONCLUSION

Results of the present analysis suggest that de novo SRL-based immunosuppression can be safely used in patients undergoing LT for HCV-associated liver disease; however, SRL-based immunosuppression did not significantly affect the timing or severity of post-transplant HCV recurrence. HCV recurrence in SRL-treated patients had lower progressive activity and fibrosis levels on serial biopsy.     

Single-dose infliximab in hepatitis C genotype 1 treatmentnaive patients with high serum levels of tumour necrosis factor-alpha does not influence the efficacy of pegylated interferon alpha-2b/ribavirin therapy

BACKGROUND:

Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response.

OBJECTIVES:

To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR).

METHODS:

The present study was a phase IIIB, randomized, prospective, open-label pilot trial conducted at eight Canadian sites. Treatment-naive HCV genotype 1-infected patients 18 to 65 years of age with high serum TNF-α values (>300 pg/mL) were randomly assigned to receive a single pretreatment induction infliximab infusion (5 mg/kg) seven days before antiviral therapy (arm A) or no pretreatment (arm B). All patients received pegylated interferon α2b (1.5 μg/kg/week) plus weight-based ribavirin (800 mg/day to 1400 mg/day) for up to 48 weeks.

RESULTS:

Eighty-five patients (arm A [n=41], arm B [n=44]; 70% male) received pegylated interferon α2b. The mean age (48.1 years), race (81% white) and METAVIR fibrosis stage (F0–2 = 79%, F3–4 = 21%) were similar between groups. Infliximab was well tolerated without attributable severe adverse events; 56.5% completed the study (arm A [n=21], arm B [n=27]). Most discontinuations were due to virological failure at weeks 12 (n=20 [23.5%]) and 24 (n=7 [8.2%]) and did not differ according to group. Numerically lower proportions of infliximab recipients achieved rapid virological response (19.5% versus 36.4%), complete early virological response (43.9% versus 59.1%) and SVR (34.1% versus 52.3%). However, between-group differences did not reach statistical significance. No differences in adverse event profile or laboratory measures were noted.

CONCLUSION:

A single infliximab dose before pegylated-interferon α2b and ribavirin therapy did not result in greater viral decline during the first 12 weeks of HCV therapy or improved SVR.     

Prevalence of Hepatitis C Virus Genotypes in Iranian Patients: A Systematic Review and Meta-Analysis

Context:

Hepatitis C virus (HCV) is a global public health problem and a major etiology of chronic liver disease, which may develop into cirrhosis and hepatocellular carcinoma. Genotypes of HCV indicate the route of acquisition, the clinical outcome, response to treatment, prognosis and control strategies.

Objectives:

The aim of this study was to estimate the overall prevalence and trend of HCV genotypes or subtypes in Iran

Data Sources:

A literature review was done for papers reporting HCV genotypes in Iranian patients in PubMed, Magiran, IranMedex, Scientific Information Databank, and Google scholar databases.

Study Selection:

Data were selected according to inclusion and exclusion criteria.

Data Extraction:

Data were abstracted by two independent authors. Data were analyzed based on random-effects model using the Meta R. Pooled statistical software. Prevalence of HCV genotypes in cities and provinces of Iran with 95% confidence interval (CI) were calculated.

Results:

Fifty-three articles published between 1999 and 31 June 2014 including 22952 HCV infected individuals were included in the meta-analysis. Subtype 1a was predominant with a rate of 39% (95% CI: 34-44%); followed by subtype 3a, 32% (95% CI: 26-39%); subtype 1b, 13% (95% CI: 10-15%); genotype 4, 5.18% (95% CI: 3.27-7.5%); and genotype 2, 3.6% (95% CI: 1.6-8.3%). Untypeable HCV had a rate of 0.11% (95% CI: 0.07-0.16%).

Conclusions:

The most frequent subtypes of HCV in Iran were 1a, 3a and 1b, respectively. This frequency differed in various provinces of Iran and fluctuated with time. It is important to determine the distribution of HCV genotypes in different geographical areas and its trend with time for epidemiological and patients’ management purposes.     

Postoperative delirium in the intensive care unit predicts worse outcomes in liver transplant recipients

BACKGROUND:

Delirium is common in intensive care unit patients and is associated with worse outcome.

OBJECTIVE:

To identify early risk factors for delirium in patients admitted to the intensive care unit following orthotopic liver transplantation (OLT).

METHODS:

An observational study of patients admitted to the intensive care unit from January 2000 to May 2010 for elective or semi-elective OLT was conducted. The primary end point was delirium in the intensive care unit. Pre- and post-transplantation and intraoperative factors potentially associated with this outcome were examined.

RESULTS:

Of the 281 patients included in the study, 28 (10.03%) developed delirium in the intensive care unit at a median of two days (interquartile range one to seven days) after OLT. According to multivariate analysis, independent risk factors for delirium were intraoperative transfusion of packed red blood cells (OR 1.15 [95% CI 1.01 to 1.18]), renal replacement therapy during the pretransplantation period (OR 13.12 [95% CI 2.82 to 72.12]) and Acute Physiologic and Health Evaluation (APACHE) II score (OR per unit increase 1.10 [95% CI 1.03 to 1.29]). Using Cox proportional hazards models adjusted for baseline covariates, delirium was associated with an almost twofold risk of remaining in hospital, a fourfold increased risk of dying in hospital and an almost threefold increased rate of death by one year.

CONCLUSION:

Intraoperative transfusion of packed red blood cells, pretransplantation renal replacement therapy and APACHE II score are predictors for the development of delirium in intensive care unit patients post-OLT and are associated with increased hospital lengths of stay and mortality.     

The Prevalence of Hepatitis C Virus Infection and Its Related Risk Factors Among the Rural Population of Fars Province,Southern Iran

Background:

Hepatitis C virus (HCV) infection is a major blood-borne infection with silent epidemic, major global public health problem and diverse prevalence worldwide.

Objectives:

This study aimed to evaluate the prevalence of HCV infection and related risk factors in the general population of two villages, Farmashkan and Akbarabad, of the Kavar City in Fars Province, Iran.

Patients and Methods:

A 34-month cross-sectional study was performed on all people of the villages aged ≥ 7 years from July 2007 to April 2010. Demographic information and history of HCV-related risk factors were extracted from their medical records. For each participant, the serum anti-HCV IgG was assessed by the commercial enzyme-linked immunosorbent assay (ELISA) kits.

Results:

A total of 6095 participants (36.4% male and 65.6% female) with the mean age of 92 (7-95) and mean ± SD of 34.6 ± 17.3 years were included in this study. Fifteen persons (0.24%) were detected as HCV-positive and the highest prevalence was seen in age ≤ 12 years old (1%). A significant association was only detected between blood transfusion and HCV infection; therefore, those persons with history of blood transfusion had 15-fold higher risk for HCV seropositivity (odds ratio 15.54, 95% CI = 4.89-49.41).

Conclusions:

Our reported rate of HCV seropositivity is similar to the previous Iranian reports. However, future evaluations should be focused on the Polymerase Chain Reaction method for the detection of HCV and determining and evaluating of other related risk factors. Moreover, more attention should be paid to blood donors as a reservoir population of HCV.     

Pretreatment resistance to hepatitis C virus protease inhibitors boceprevir/telaprevir in hepatitis C subgenotype 1a-infected patients from Manitoba

BACKGROUND:

Traditional therapy with pegylated interferon and ribavirin combined with the new protease inhibitors boceprevir or telaprevir has demonstrated improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data regarding pre-existing drug-resistant variants to these two new virus inhibitors in the Canadian population are not available.

OBJECTIVE:

To detect pre-existing mutations conferring resistance to boceprevir and/or telaprevir in Canadian patients infected with HCV genotype 1a.

METHODS:

Resistance-associated mutations (RAMs) were evaluated in 85 patients infected with HCV genotype 1a who had not yet received antiviral therapy. The NS3 protease gene was sequenced and common RAMs were identified based on a recently published list.

RESULTS:

The overall prevalence of pre-existing RAMs to boceprevir and telaprevir was higher compared with other similar studies. All of the observed RAMs were associated with a low level of resistance. A surprisingly high proportion of patients had the V55A RAM (10.6%). None of the mutations associated with a high level of resistance were observed. The simultaneous presence of two low-level resistance mutations (V36L and V55A) was observed in only one patient. Three other patients had both T54S RAM and V55I mutations, which may require a higher concentration of the protease drugs. The prevalence of various mutations in Aboriginal Canadian patients was higher (37.5%) compared with Caucasians (16.39%) (P=0.038).

CONCLUSIONS:

The present study was the first to investigate pre-existing drug resistance to boceprevir/telaprevir in Canadian HCV-infected patients. A relatively high proportion of untreated HCV genotype 1a patients in Manitoba harbour low-level RAMs, especially patients of Aboriginal descent, which may contribute to an increased risk of treatment failure.     

Patient characteristics and outcomes of a provincial prolonged-ventilation weaning centre: A retrospective cohort study

BACKGROUND:

Growing numbers of critically ill patients require prolonged mechanical ventilation and experience difficulty with weaning. Specialized centres may facilitate weaning through focused interprofessional expertise with an emphasis on rehabilitation.

OBJECTIVE:

To characterize the population of a specialized prolonged-ventilation weaning centre (PWC) in Ontario, and to report weaning, mobility, discharge and survival outcomes.

METHODS:

Data from consecutively admitted patients were retrospectively extracted from electronic and paper medical records by research staff and verified by the primary investigator.

RESULTS:

From January 2004 to March 2011, 144 patients were admitted: 115 (80%) required ventilator weaning, and 29 (20%) required tracheostomy weaning or noninvasive ventilation. Intensive care unit length of stay before admission was a median 51 days (interquartile range [IQR] 35 to 86 days). Of the patients admitted for ventilator weaning, 76 of 115 (66% [95% CI 55% to 75%]) achieved a 24 h tracheostomy mask trial in a median of 15 days (IQR eight to 25 days). Weaning success, defined as no further ventilation for seven consecutive days, was achieved by 61 patients (53% [95% CI 44% to 62%]) in a median duration of 62 days (IQR 46 to 95 days) of ventilation, and 14 days (IQR nine to 29 days) after PWC admission. Seventeen patients died during admission. Of the 91 patients discharged from the PWC for one year, 43 (47.3% [95% CI 37.3% to 57.4%]) survived; of the 78 discharged for two years, 27 (34.6% [95% CI 25.0% to 45.7%]) were alive; of the 53 discharged for three years, 19 (35.9% [95% CI 24.3% to 49.3%]) were alive; and seven of 22 (31.8% [95% CI 16.4% to 52.7%]) survived to five years.

CONCLUSIONS:

Weaning success was moderate despite a prolonged intensive care unit stay before admission, but was comparable with studies reporting weaning outcomes from centres in other countries. Few patients survived to five years.     

Health care costs associated with hepatitis C: a longitudinal cohort study

BACKGROUND

Disease-specific estimates of medical costs are important for health policy decision making.

OBJECTIVE

To identify predictors of health care costs associated with hepatitis C virus (HCV) seropositivity across disease phases.

METHODS

HCV laboratory tests from the BC Centre for Disease Control were linked to administrative data pertaining to health services and drugs dispensed to estimate costs among case subjects and controls. The case group comprised HCV seropositive individuals (n=20,001), and the control group comprised single-tested, HCV seronegative persons (n=70,752) identified between January 1997 and December 2004. Subject observation time was assigned to the three following disease phases: initial phase (after diagnosis), late phase (late-stage liver disease) and predeath phase (12 months before death). Case subjects and controls were matched for age, sex and a propensity score within each phase to determine the net cost attributable to HCV seropositivity, and were adjusted for demographic and clinical factors.

RESULTS

Costs increased with disease progression, with hospitalization being the highest cost component in all phases. Initial and late phase net costs (2005 Canadian dollars) were $1,850 and $6,000 per patient per year, respectively. Costs among case subjects were driven by age, comorbidities, mental illness, illicit drug use and HIV coinfection. While predeath case subject and control costs were virtually the same, costs were high and case subjects died at a younger age.

CONCLUSION

HCV seropositivity is associated with increased medical costs driven by viral sequelae and medicosocial vulnerabilities (ie, mental illness, illicit drug use and HIV coinfection). Cost mitigation and health outcome improvements will require broad-based prevention programming to reduce vulnerabilities and HCV treatment to prevent disease progression, respectively.     

The interaction between insulin resistance, liver fibrosis and early virological response in Egyptian patients with chronic hepatitis C

BACKGROUND:

Hepatitis C virus (HCV) infection may induce insulin resistance (IR) irrespective of the severity of liver disease, and there is evidence of a central role for IR in failure to achieve sustained virological response (SVR) in HCV patients.

OBJECTIVE:

To assess IR as a predictor of the severity of hepatic fibrosis in Egyptian HCV patients, and its effect on early viral kinetics and virological response to HCV therapy.

METHODS:

A total of 140 chronic HCV patients were divided into two groups according to the homeostasis model assessment-IR (HOMA-IR). Group 1 consisted of 48 chronic HCV patients with HOMA-IR ≥2, and group 2 consisted of 92 chronic HVC patients without IR (HOMA IR <2). All patients were treated with combination therapy (pegylated interferon-alpha 2a plus ribavirin) for 48 weeks and studied for viral kinetics throughout the period of therapy.

RESULTS:

The study revealed that older age, higher body mass index and HOMA-IR≥2 were significantly associated with advanced fibrosis. Rapid virological response, complete early virological response and SVR were significantly lower in the IR-HCV group compared with the non-IR-HCV group. Univariate and multivariate analyses revealed that older age, fibrosis (F≥3), high viral load (>600,000 IU/mL) and HOMA-IR ≥2 were significantly associated with a lack of viral kinetics as well as SVR. However, HOMA-IR ≥2 was the main independent variable associated with lack of SVR. On the other hand, body mass index, plasma insulin level and HOMA-IR decreased significantly compared with starting levels in patients who achieved SVR. This suggests a cause and effect relationship between HCV infection and IR.

CONCLUSION:

IR in chronic HCV patients is associated with progressive fibrosis and slow viral kinetics, and could be a predictor for lack of rapid and early virological response. Therefore, HOMA-IR levels should be measured and improved before starting antiviral treatment.