Health care costs associated with hepatitis C virus infection in First Nations populations in Ontario: a retrospective matched cohort study.

BACKGROUND: Colonization and marginalization have affected the risk for and experience of hepatitis C virus (HCV) infection for First Nations people in Canada. In partnership with the Ontario First Nations HIV/AIDS Education Circle, we estimated the publicly borne health care costs associated with HCV infection among Status First Nations people in Ontario. METHODS: In this retrospective matched cohort study, we used linked health administrative databases to identify Status First Nations people in Ontario who tested positive for HCV antibodies or RNA between 2004 and 2014, and Status First Nations people who had no HCV testing records or only a negative test result (control group, matched 2:1 to case participants). We estimated total and net costs (difference between case and control participants) for 4 phases of care: prediagnosis (6 mo before HCV infection diagnosis), initial (after diagnosis), late (liver disease) and terminal (6 mo before death), until death or Dec. 31, 2017, whichever occurred first. We stratified costs by sex and residence within or outside of First Nations communities. All costs were measured in 2018 Canadian dollars. RESULTS: From 2004 to 2014, 2197 people were diagnosed with HCV infection. The mean net total costs per 30 days of HCV infection were $348 (95% confidence interval [CI] $277 to $427) for the prediagnosis phase, $377 (95% CI $288 to $470) for the initial phase, $1768 (95% CI $1153 to $2427) for the late phase and $893 (95% CI -$1114 to $3149) for the terminal phase. After diagnosis of HCV infection, net costs varied considerably among those who resided within compared to outside of First Nations communities. Net costs were higher for females than for males except in the terminal phase. INTERPRETATION: The costs per 30 days of HCV infection among Status First Nations people in Ontario increased substantially with progression to advanced liver disease and finally to death. These estimates will allow for planning and evaluation of provincial and territorial population-specific hepatitis C control efforts.

Diagnostic accuracy of hepatocyte growth factor, Fas/CD95 and Endostatin for non-invasive assessment of hepatic fibrosis in biopsy-proven hepatitis C virus patients.

BACKGROUND/AIM: Evaluation of liver fibrosis in chronic hepatitis C patients (CHC) provides a high value, not only for the diagnosis of the disease, but also for the therapeutic decision. The aim of the current study is the construction of simple non-invasive and more accurate score for liver fibrosis staging in CHC patients and estimating its performance against three published non-invasive indexes. MATERIAL AND METHODS: CHC patients were divided into two groups: an estimated group (n = 75) and validated group (n = 50). Liver fibrosis was tested in biopsies by Metavair score system. Fas/CD95, hepatocyte growth factor (HGF) and endostatin were assayed by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed by stepwise linear discriminate analysis and area under-receiver operating curves (AUCs). RESULTS: The multivariate discriminate analysis (MDA) selects a function based on absolute values of five biochemical markers; FHEPA (Fas/CD95, HGF, Endostatin, Platelets&Albumin)-Test score = 1.2 × Fas/CD95 (ng/mL) + 0.006 × HGF (pg/mL) + 0.03 × Endostatin (ng/mL) - 0.007 × platelets count(109/L)-3.6 × Albumin (g/dL) - 8.6.FHEPA-Test producesAUCs 0.99, 0.877 and 0.847 to discriminate patients with significant fibrosis (F2-F4), advanced fibrosis (F3-F4) and cirrhosis (F4), respectively. CONCLUSION: FHEPA-Test is considered a novel non-invasive test which could be applied in assessment of liver fibrosis in HCV infected patients. Our novel score was more efficient than Immune Fibrosis Index, Fibrosis Index and FibroQ and thus it could be more applicable, feasible & economic for Egyptian HCV patients. Our Novel Scoring system could be globalized to other populations to confirm its advantageous use in early diagnosis of liver fibrosis.

Ultrasonic assessment of liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis.

BACKGROUND: This study investigated the relationship between liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis. We used an acoustic radiation force impulse (ARFI) technique to measure stiffness, and a radio frequency (RF) vascular quantitative ultrasound technique to measure changes in common carotid artery elasticity and vascular function. METHODS: Two-hundred seventeen patients with chronic viral hepatitis caused by either hepatitis B virus (HBV) or hepatitis C virus (HCV) were enrolled. We divided the patients into two groups, one comprising 147 patients with chronic hepatitis B (CHB) (98 men and 49 women, average age 46.5 ± 12.2 years) and another comprising 70 patients with chronic hepatitis C (CHC) (47 men and 23 women, average age 47.6 ± 12.1 years). Additionally, 64 healthy age- and sex-matched participants (43 men and 21 women, average age 47.8 ± 5.1 years) were selected as the control group. The ARFI technique was used to measure liver stiffness and the RF ultrasound technique was used to measure carotid artery elasticity parameters including intima-media thickness (IMT), pulse wave velocity (PWV), arterial wall dilation coefficient (DC), compliance coefficient (CC), sclerosis indices α and ß, and augmentation index (Aix). Clinical indicators, liver stiffness, and carotid artery elasticity parameters were observed and compared between the different age groups to investigate the correlation between carotid artery elasticity parameters and liver stiffness. RESULTS: The ARFI values for the CHB and CHC groups were significantly higher than those for the control group (1.84 ± 0.52 vs. 1.04 ± 0.11 m/s; 1.86 ± 0.37 vs. 1.04 ± 0.11 m/s, respectively; P < 0.001). When compared to the control group, both CHB and CHC groups showed an IMT of the same order, but had significantly higher elasticity parameters, such as α and ß, as well as lower DC and CC values (P < 0.001). The PWV of the CHC group was significantly higher than that of the control group (7.98 ± 1.42 vs. 6.09 ± 0.90 m/s, P < 0.001). In the CHB group, all parameters including ARFI, IMT, PWV, DC, CC, α and ß, were significantly different between the two age groups (P < 0.05). Within the CHC group, all parameters including IMT, PWV, DC, α and ß, were significantly different between the two age groups (P < 0.05), except for ARFI, wherein the difference was not statistically significant. The correlation analysis and stepwise multiple linear regression analysis indicated that for patients with CHB, age was an independent predictor of common carotid artery IMT (R2 = 0.468, F = 54.635, and P < 0.001). For patients with CHC, age and blood sugar were independent predictors of common carotid artery IMT (R2 = 0.465, F = 29.118, and P < 0.001). CONCLUSION: Although based on ARFI and RF ultrasound, the carotid artery IMT in patients with CHB and CHC was not significantly higher than that in the control group, their functional elasticity parameters had already changed. This finding serves as a useful reference for the clinical diagnosis of vascular diseases in patients with viral hepatitis. TRIAL REGISTRATION: ClinicalTrials: ChiCTR1800015859 25/04/2018.

Risk of rheumatoid arthritis in patients with hepatitis C virus infection receiving interferon-based therapy: a retrospective cohort study using the Taiwanese national claims database.

OBJECTIVES: To illuminate the association between interferon-based therapy (IBT) and the risk of rheumatoid arthritis (RA) in patients infected with hepatitis C virus (HCV). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This retrospective cohort study used Taiwan's Longitudinal Health Insurance Database 2005 that included 18 971 patients with HCV infection between 1 January 1997 and 31 December 2012. We identified 1966 patients with HCV infection who received IBT (treated cohort) and used 1:4 propensity score-matching to select 7864 counterpart controls who did not receive IBT (untreated cohort). OUTCOME MEASURES: All study participants were followed until the end of 2012 to calculate the incidence rate and risk of incident RA. RESULTS: During the study period, 305 RA events (3.1%) occurred. The incidence rate of RA was significantly lower in the treated cohort than the untreated cohort (4.0 compared with 5.5 per 1000 person-years, p<0.018), and the adjusted HR remained significant at 0.63 (95% CI 0.43 to 0.94, p=0.023) in a Cox proportional hazards regression model. Multivariate stratified analyses revealed that the attenuation in RA risk was greater in men (0.35; 0.15 to 0.81, p=0.014) and men<60 years (0.29; 0.09 to 0.93, p=0.036). CONCLUSIONS: This study demonstrates that IBT may reduce the risk of RA and contributes to growing evidence that HCV infection may lead to development of RA.

The impact of nutrition on quality of life of patients with hepatitis C.

PURPOSE OF REVIEW: The aim of this study was to review the most recent aspects of nutrition and its impact on health-related quality of life (HRQOL) in patients with chronic hepatitis C (CHC). RECENT FINDINGS: Low HRQOL scores have been found in all stages of hepatitis C virus (HCV) infection. Of the factors linked to HRQOL, three aspects should be emphasized, nutritional status, physical activity and mental health status. Regarding the nutrition and metabolic conditions, a broad spectrum of nutritional disorders may impact on HRQOL of patients with CHC. SUMMARY: Malnutrition, which is a significant comorbidity in end-stage of all chronic liver diseases, has been recognized as a significant factor related to poor HRQOL. Of note, in individuals chronically infected with HCV, low muscle skeletal mass, an early indicator of undernourishment, precedes the development of cirrhosis. Because of the strict linkage between HRQOL, nutrition and physical activity, the assessment of the musculoskeletal system abnormalities in every patient with CHC, independently of the stage of the liver disease, is of utmost relevance. Maintenance of healthy skeletal muscle is essential to reduce the negative effects of sarcopenia on HRQOL. Otherwise, overweight/obesity and chronic HCV infection can cause insulin resistance, which has been associated with HRQOL impairment.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). CONCLUSION: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).

Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

BACKGROUND: In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. RESEARCH DESIGN AND METHODS: In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. MAIN OUTCOME MEASURES: Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. RESULTS: The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. LIMITATIONS: Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. CONCLUSIONS: These results suggest that liver disease progression varies by genotype and that CHC patients with GT3 appear to have more severe liver disease. These findings highlight the importance of effective HCV treatment for all patients and support guidelines for treatment of high-risk patients, including those with GT3.

Human immunodeficiency virus-infected and uninfected adults with non-genotype 3 hepatitis C virus have less hepatic steatosis than adults with neither infection.

Hepatic steatosis (HS) is common in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, but the independent contributions of HCV and HIV to HS are unclear. Magnetic resonance imaging and spectroscopy were used to measure visceral adipose tissue (VAT) and liver fat fraction (LFF) (total lipids/[total lipids + water]) in 356 adults: 57 with HCV monoinfection, 70 with HIV/HCV coinfection, 122 with HIV monoinfection, and 107 with neither infection. Participants who were infected with HCV genotype 3 were excluded because of the genotype's reported steatogenic effects. For prevalence estimates, HS was defined as LFF ≥ 0.05. We estimated the association of HIV and HCV status with LFF using multivariable linear regression, adjusting for demographics, lifestyle, and metabolic factors including the homeostasis model assessment estimate of insulin resistance (HOMA-IR) and liver fibrosis defined using the aspartate aminotransferase-to-platelet ratio index (APRI). The prevalence of HS was highest in the uninfected (33%) and HIV-monoinfected (28%), followed by the HCV-monoinfected (19%) and HIV/HCV-coinfected (11%) (P = 0.003 across groups). Compared with uninfected participants-and after adjusting for demographics, lifestyle, and metabolic factors-HIV monoinfection, HCV monoinfection, and HIV/HCV coinfection were associated with 19% (95% confidence interval [CI], -39% to 6%), 38% (95% CI, -55% to -12%), and 42% (95% CI, -59% to -18%) lower LFF, respectively. HCV monoinfection and HIV/HCV coinfection remained strongly associated with lower LFF after further adjusting for APRI, and results were unchanged after excluding subjects with suspected cirrhosis. Among the entire cohort, Hispanic ethnicity, male sex, VAT, and HOMA-IR were independently associated with greater LFF. CONCLUSION: Contrary to expectations, HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjusting for demographics, lifestyle, metabolic factors, and hepatic fibrosis. Our findings suggest that non-genotype 3 HCV infection may be protective against HS. The mechanisms by which this occurs and the impact of HCV treatment on HS requires further investigation. (Hepatology 2017;65:853-863).

Predictors of high healthcare resource utilization and liver disease progression among patients with chronic hepatitis C.

BACKGROUND: Since hepatitis C virus therapy is typically prioritized for patients with more advanced disease, predicting which patients will progress could help direct scarce resources to those likely to benefit most. This study aims to identify demographics and clinical characteristics associated with high healthcare resource utilization (HRU) and liver disease progression among CHC patients. METHODS: Using health insurance claims (January 2001-March 2013), adult patients with ≥2 CHC claims (ICD-9-CM: 070.44 or 070.54), and ≥6 months of continuous insurance coverage before and ≥36 months after the first CHC diagnosis were included. Patients with human immunodeficiency virus were excluded. Generalized estimating equations were used to identify the demographic and clinical characteristics of being in the 20% of patients with the highest HRU. Factors predicting liver disease progression were also identified. RESULTS: In the study population (n = 4898), liver disease severity and both CHC- and non-CHC-related comorbidities and conditions were strong predictors of high healthcare costs, with odds ratios (ORs; 95% confidence interval [CI]) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities/conditions of 2.78 (2.48-3.12) and 2.19 (1.76-2.72), respectively. CHC- and non-CHC-related comorbidities and conditions were also strong predictors of liver disease progression with ORs (95% CI) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities and conditions of 2.18 (1.83-2.60) and 1.50 (1.14-1.97), respectively. LIMITATIONS: Potential inaccuracies in claims data, information or classification bias, and findings based on a privately insured population. CONCLUSION: This study suggests that CHC patients with high healthcare resource utilization have a high level of comorbidity at baseline and also that non-CHC comorbidities and conditions are strong predictors of high HRU. Non-cirrhotic CHC patients with one or more comorbidities are at high risk of progressing to cirrhosis or end-stage liver disease.

Cost-effectiveness analysis of simeprevir in combination with peginterferon and ribavirin for treatment-naïve chronic hepatitis C genotype 1 patients in Japan.

AIM: Simeprevir (SMV), a protease inhibitor, recently became available for the treatment of chronic hepatitis C (HCV) genotype 1 patients in Japan. The introduction of triple therapy using SMV in combination with peginterferon and ribavirin (PR) significantly improves the cure rate. The aim was to assess the cost-effectiveness of SMV with PR (SMV/PR) compared to telaprevir with PR (TVR/PR), PR alone, or no treatment in treatment-naïve patients in Japan. METHODS: A Markov model was developed to reflect the natural disease progression of HCV and to estimate the average life years and lifetime healthcare costs per patient. Sustained virologic response rates were obtained from a network meta-analysis including randomized clinical trials conducted in Japan. Patient baseline characteristics, HCV progression rates, mortality, medical resource utilization, and unit costs were obtained from Japanese sources. Outcomes were reported as incremental cost-effectiveness ratios as well as incremental cost and life years. Various sensitivity analyses were conducted to assess the uncertainty around model outcomes. RESULTS: SMV/PR was estimated to be a cost-effective treatment option as more life years were gained by 0.235 and 0.873 years at a reduced cost by ¥263,037 and ¥776,900 compared to TVR/PR and PR alone, respectively. The results were robust to sensitivity analyses, in particular in the comparison of SMV/PR with PR alone. The multivariate probabilistic sensitivity analyses showed that the probability of SMV/PR being cost-effective was relatively constant at ∼87% at any willingness to pay. CONCLUSIONS: SMV/PR is estimated to be the most cost-effective treatment strategy for treatment-naïve HCV genotype 1 patients in Japan.

Egy-score as a noninvasive score for the assessment of hepatic fibrosis in chronic hepatitis C: a preliminary approach.

BACKGROUND AND AIMS: Egy-Score is a new noninvasive score for prediction of severe hepatic fibrosis in patients with chronic liver diseases. The aim of this study was to validate Egy-Score as a noninvasive score for predicting stage of hepatic fibrosis in a group of Egyptian chronic hepatitis C patients. PATIENTS AND METHODS: One hundred Egyptian patients with chronic hepatitis C were enrolled. Mean age was 40.25 ± 9.39 years. They were subjected to CA19-9, alpha-2-macroglobulin, total bilirubin, platelet count and albumin, liver biopsy, and histopathological staging of hepatic fibrosis according to METAVIR scoring system as part of their assessment for treatment. Egy-Score was calculated according to the following formula: Egy-Score = 3.52 + 0.0063 × CA19-9 + 0.0203 × age + 0.4485 × alpha-2-macroglobulin + 0.0303 × bilirubin - 0.0048 × platelet - 0.0462 × albumin. Egy-Score results were correlated to the stage of hepatic fibrosis. RESULTS: Egy-Score correlates positively with the stage of hepatic fibrosis (F0-F4). Egy-Score was able to differentiate significant hepatic fibrosis, severe hepatic fibrosis, and cirrhosis accurately. Cutoff values of Egy-Score were 2.91850 (for significant fibrosis), 3.28624 (for severe fibrosis), and 3.67570 (for cirrhosis). Sensitivity, specificity, and areas-under-ROC curve (AUROCs) were 75.8%, 68.42%, and 0.776 (for significant fibrosis "≥F2"), 91.67%, 77.63%, and 0.875 (for severe fibrosis "≥F3"), and 81.82%, 86.52%, and 0.874 (for cirrhosis "F4"), respectively. CONCLUSION: Egy-Score is a useful noninvasive panel of surrogate biomarkers that could accurately predict different stages of hepatic fibrosis in patients with chronic hepatitis C.

Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

BACKGROUND/AIMS: Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage.

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography.

AIM: To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC). METHODS: Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness. RESULTS: A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043). CONCLUSION: Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.

Economic burden of hepatitis C-associated diseases: Europe, Asia Pacific, and the Americas.

BACKGROUND: Globally, hepatitis C virus (HCV) infects ∼3% of the population. The objective of this study was to review published work and determine the direct medical costs for diseases associated with HCV infection globally, with the exception of the US. METHODS: A systematic literature search was conducted to identify studies reporting the costs of hepatitis C sequelae between January 1990 and January 2011. Over 400 references were identified, of which 45 were pertinent. The costs were compiled, converted to US dollars, and adjusted to 2010 costs using the medical component of the consumer price index. RESULTS: The median cost of liver transplants was estimated at $139,070 ($15,430-$443,700), refractory ascites at $16,740 ($8990-$35,940), hepatocellular carcinoma (HCC) at $15,310 ($3370-$84,710), decompensated cirrhosis at $14,660 ($3810-$48,360), variceal hemorrhage at $12,190 ($3550-$46,120), hepatic encephalopathy at $9180 ($5370-$50,120), diuretic sensitive ascites at $3400 ($1320-$7470), compensated cirrhosis at $820 ($50-$2890), and chronic hepatitis C at $280 ($90-$1860). The variation among studies was mainly due to the methodology used to assess cost, local cost and government reimbursement, and country-specific treatment protocols. LIMITATIONS: All costs were adjusted to 2010 US dollars using the US medical component of the consumer price index (CPI) which may not reflect the change in medical costs in other countries. In addition, the costs, in the local currency were converted to US dollars in the year of the study. However, medical expenses may not vary with exchange rate, leading to artificial variations. Finally, there was no assessment of the quality of individual studies, which resulted in the same weighting to all studies. CONCLUSIONS: Hepatitis C imposes a high economic burden globally. Knowing the burden of HCV sequelae is useful for policy decisions as well as serving as a basis for determining the value of HCV screening and treatment.

Non-invasive assessment of fibrosis using color Doppler ultrasound in patients with hepatitis C virus in the Amazon rainforest, Brazil.

The purpose of this study was to correlate morphologic and hemodynamic Doppler ultrasound findings as indicators of the degree of inflammation and fibrosis and to diagnose chronic vital hepatitis complications and progression. A prospective, descriptive study of a case series was conducted that analyzed Doppler ultrasound images of the liver and portal system and used the portal vein congestion index, hepatic and splenic artery impedance indices, and the liver vascular index. Of 50 patients positive for antibodies against hepatitis C virus, morphologic changes highlighted increased hepatic parenchyma echogenicity in 24%, and increased gall blander echogenicity and wall thickness in 4%. The most common hemodynamic changes observed were reduced flow velocity in the portal vein trunk in 26%, congestion index changes in 12%, liver vascular index changes in 16%, and splenic and hepatic artery impedance index changes in 14%. These indices were shown to be associated with alanine aminotransferase levels, which suggested that they are important liver damage indicators in the early phase of infection with hepatitis C virus.

Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention.

BACKGROUND & AIMS: Hepatitis C virus (HCV) screening can provide opportunities to reduce disease progression through counseling against alcohol use, but empirical data on this issue are sparse. We determined the efficacy of a behavioral intervention in reducing alcohol use among young, HCV-infected injection drug users (IDUs) (n=355) and assessed whether changes in liver enzymes were associated with changes in alcohol consumption. METHODS: Both the intervention and attention-control groups were counseled to avoid alcohol use, but the intervention group received enhanced counseling. Logistic regression, ANOVA, and continuous time Markov models were used to identify factors associated with alcohol use, changes in mean ALT and AST levels, and change in alcohol use post-intervention. RESULTS: Six months post-intervention, alcohol abstinence increased 22.7% in both groups, with no difference by intervention arm. Transition from alcohol use to abstinence was associated with a decrease in liver enzymes, with a marginally greater decrease in the intervention group (p=0.05 for ALT; p=0.06 for AST). In multivariate Markov models, those who used marijuana transitioned from alcohol abstinence to consumption more rapidly than non-users (RR=3.11); those who were homeless transitioned more slowly to alcohol abstinence (RR=0.47); and those who had ever received a clinical diagnosis of liver disease transitioned more rapidly to abstinence (RR=1.88). CONCLUSIONS: Although, behavioral counseling to reduce alcohol consumption among HCV-infected IDUs had a modest effect, reductions in alcohol consumption were associated with marked improvements in liver function. Interventions to reduce alcohol use among HCV-infected IDUs may benefit from being integrated into clinical care and monitoring of HCV infection.

The homeostasis model assessment of the insulin resistance score is not predictive of a sustained virological response in chronic hepatitis C patients.

OBJECTIVES: To investigate the independent association between the homeostasis model assessment of the insulin resistance (HOMA-IR) score and rapid virological response (RVR) and sustained virological response (SVR) in chronic hepatitis C (CHC). METHODS: Observational prospective cohort study of 412 CHC patients [59% males; mean age 45 years; genotype 1 (44%), 2 (32%), 3 (19%) and 4 (5%)] treated with pegylated interferon α plus ribavirin. RESULTS: A HOMA-IR ≥2.0 was present in 49% and a metabolic syndrome in 4% of patients. By multivariate analysis, independent predictors of SVR were the lack of advanced fibrosis (≥F3) in genotype 1 and a lower body mass index in genotype 3 patients. In the subgroup of patients in whom HCV-RNA was evaluated at week 4 (n = 281), independent predictors of RVR were HCV-RNA <700,000 IU/ml, age <40 years and lower aspartate aminotransferase:alanine aminotransferase ratio in genotype 1 and baseline HOMA-IR ≤2 in genotype 3 patients. No predictive factor of RVR was identified among genotype 2 patients. RVR was the strongest predictor of SVR among genotype 1 or 3 patients. CONCLUSIONS: In this series of treatment-naïve, Caucasian CHC patients at a low risk for the metabolic syndrome, HOMA-IR is not a predictor of SVR, irrespective of the HCV genotype, although it may predict RVR in genotype 3 infection.

Non-Markov multistate modeling using time-varying covariates, with application to progression of liver fibrosis due to hepatitis C following liver transplant.

Multistate modeling methods are well-suited for analysis of some chronic diseases that move through distinct stages. The memoryless or Markov assumptions typically made, however, may be suspect for some diseases, such as hepatitis C, where there is interest in whether prognosis depends on history. This paper describes methods for multistate modeling where transition risk can depend on any property of past progression history, including time spent in the current stage and the time taken to reach the current stage. Analysis of 901 measurements of fibrosis in 401 patients following liver transplantation found decreasing risk of progression as time in the current stage increased, even when controlled for several fixed covariates. Longer time to reach the current stage did not appear associated with lower progression risk. Analysis of simulation scenarios based on the transplant study showed that greater misclassification of fibrosis produced more technical difficulties in fitting the models and poorer estimation of covariate effects than did less misclassification or error-free fibrosis measurement. The higher risk of progression when less time has been spent in the current stage could be due to varying disease activity over time, with recent progression indicating an "active" period and consequent higher risk of further progression.

Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography.

UNLABELLED: Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV-RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow-up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person-year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM < or =10 kPa, of 16.7 (95% confidence interval [CI], 3.71-75.2; P < 0.001) when LSM 10.1-15 kPa, 20.9 (95% CI, 4.43-98.8; P < 0.001) when LSM 15.1-20 kPa, 25.6 (95%CI, 5.21-126.1; P < 0.001) when LSM 20.1-25 kPa, and 45.5 (95% CI, 9.75-212.3; P < 0.001) when LSM >25 kPa. CONCLUSIONS: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development.

Prognosis of hepatitis C virus-infected Canadian post-transfusion compensation claimant cohort.

Accurate prognostic estimates were required to ensure the sufficiency of the $1.1 billion compensation fund established in 1998 to compensate Canadians who acquired hepatitis C virus (HCV) infection through blood transfusion between 1986 and 1990. This article reports the application of Markov modelling and epidemiological methods to estimate the prognosis of individuals who have claimed compensation. Clinical characteristics of the claimant cohort (n = 5004) were used to define the starting distribution. Annual stage-specific transition probabilities (F0-->F1, . . ., F3-->F4) were derived from the claimants, using the Markov maximum likelihood estimation method. HCV treatment efficacy was derived from the literature and practice patterns were estimated from a national survey. The estimated stage-specific transition probabilities of the cohort between F0-->F1, F1-->F2, F2-->F3 and F3-->F4 were 0.032, 0.137, 0.150 and 0.097 respectively. At 20 years after the index transfusion, approximately 10% of all living claimants (n = 3773) had cirrhosis and 0.5% developed hepatocellular carcinoma (HCC). For nonhaemophilic patients, the predicted 20-year (2030) risk of HCV-related cirrhosis was 23%, and the risk of HCC and liver-related death was 7% and 11% respectively. Haemophilic patients who are younger and are frequently co-infected with human immunodeficiency virus would have higher 20-year risks of cirrhosis (37%), HCC (12%) and liver-related death (19%). Our results indicate that rates of progression to advanced liver disease in post-transfusion cohorts may be lower than previously reported. The Canadian post-transfusion cohort offers new and relevant prognostic information for post-transfusion HCV patients in Canada and is an invaluable resource to study the natural history and resource utilization of HCV-infected individuals in future studies.