Non-Invasive Evaluation of Hepatic Fibrosis: The Diagnostic Performance of Magnetic Resonance Elastography in Patients with Viral Hepatitis B or C

Purpose

To compare the accuracy of magnetic resonance elastography (MRE) with that of aspartate aminotransferase-to-platelet ratio index (APRI) for estimating the stage of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection.

Materials and Methods

We retrospectively enrolled 160 patients with chronic hepatitis and 25 healthy living liver donors. Fibrosis stage (METAVIR, F0 to F4) was determined histopathologically for all patients. APRI was recorded at the time of histopathologic examination and liver stiffness values were measured on MRE quantitative stiffness maps. The cutoff values, sensitivity, and specificity of MRE and APRI for each fibrosis stage were determined using receiver operating characteristic (ROC) analysis.

Results

MRE had a significantly greater area under the ROC curve than APRI score for discriminating among METAVIR stages F2-F4. Using a cutoff value of 2.80 kPa, MRE had a sensitivity of 94.4% and a specificity of 97.8% for detecting significant fibrosis (≥F2). There were no significant differences in fibrosis stage between patients with HBV and those with HCV infection. For ≥F2, the cutoffs were 2.47 kPa (100% sensitivity), 2.80 kP (maximum sum of sensitivity and specificity), and 3.70 kPa (100% specificity).

Conclusions

MRE is a more accurate modality than APRI for detecting significant fibrosis in patients with chronic HBV or HCV infection. Antiviral treatment should be considered in patients with liver stiffness values ≥ 2.8 kPa.     

Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

Background and Aim

Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as potential biomarkers for clinically significant and advanced fibrosis.

Methods

Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy.

Results

Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p<0.05), while the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (p<0.05). C1M showed no difference between fibrosis stages. Using Receiver Operating Characteristics analysis, the best marker for detecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0.75 and AUC = 0.86. Combination of Pro-C3 and C4M with age, BMI and gender in a multiple ordered logistic regression model improved the diagnostic value for detecting ≥F2 and ≥F3 with AUC = 0.80 and AUC = 0.88.

Conclusion

The Pro-C3 protein fragment provided clinically relevant diagnostic accuracy as a single marker of liver fibrosis. A model combining Pro-C3 and C4M along with patient’s age, body mass index and gender increased the diagnostic power for identifying clinically significant fibrosis.     

Modeling the Health and Economic Burden of Hepatitis C Virus in Switzerland

Background

Chronic hepatitis C virus infection is a major cause of liver disease in Switzerland and carries a significant cost burden. Currently, only conservative strategies are in place to mitigate the burden of hepatitis C in Switzerland. This study expands on previously described modeling efforts to explore the impact of: no treatment, and treatment to reduce HCC and mortality. Furthermore, the costs associated with untreated HCV were modeled.

Methods

Hepatitis C disease progression and mortality were modeled. Baseline historical assumptions were collected from the literature and expert interviews and strategies were developed to show the impact of different levels of intervention (improved drug cure rates, treatment and diagnosis) until 2030.

Results

Under the historical standard of care, the number of advanced stage cases was projected to increase until 2030, at which point the annual economic burden of untreated viremic infections was projected to reach €96.8 (95% Uncertainty Interval: €36 – €232) million. Scenarios to reduce HCV liver-related mortality by 90% by 2030 required treatment of 4,190 ≥F2 or 3,200 ≥F3 patients annually by 2018 using antivirals with a 95% efficacy rate. Delaying the implementation of these scenarios by 2 or 5 years reduced the impact on mortality to 75% and 57%, respectively.

Conclusions

With today’s treatment efficacy and uptake rates, hepatitis C disease burden is expected to increase through 2030. A substantial reduction in disease burden can be achieved by means of both higher efficacy drugs and increased treatment uptake. However, these efforts cannot be undertaken without a simultaneous effort to diagnose more infections.     

Hepatitis C Related Chronic Liver Cirrhosis: Feasibility of Texture Analysis of MR Images for Classification of Fibrosis Stage and Necroinflammatory Activity Grade

Purpose

To assess the feasibility of texture analysis for classifying fibrosis stage and necroinflammatory activity grade in patients with chronic hepatitis C on T2-weighted (T2W), T1-weighted (T1W) and Gd-EOB-DTPA-enhanced hepatocyte-phase (EOB-HP) imaging.

Materials and methods

From April 2008 to June 2012, MR images from 123 patients with pathologically proven chronic hepatitis C were retrospectively analyzed. Texture parameters derived from histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model and wavelet transform methods were estimated with imaging software. Fisher, probability of classification error and average correlation, and mutual information coefficients were used to extract subsets of optimized texture features. Linear discriminant analysis in combination with 1-nearest neighbor classifier (LDA/1-NN) was used for lesion classification. In compliance with the software requirement, classification was performed based on datasets from all patients, the patient group with necroinflammatory activity grade 1, and that with fibrosis stage 4, respectively.

Results

Based on all patient dataset, LDA/1-NN produced misclassification rates of 28.46%, 35.77% and 20.33% for fibrosis staging and 34.15%, 25.20% and 28.46% for necroinflammatory activity grading in T2W, T1W and EOB-HP images. In the patient group with necroinflammatory activity grade 1, LDA/1-NN yielded misclassification rates of 5.00%, 0% and 12.50% for fibrosis staging in T2W, T1W and EOB-HP images respectively. In the patient group with fibrosis stage 4, LDA/1-NN yielded misclassification rates of 5.88%, 12.94% and 11.76% for necroinflammatory activity grading in T2W, T1W and EOB-HP images respectively.

Conclusion

Texture quantitative parameters of MR images facilitate classification of the fibrosis stage as well as necroinflammatory activity grade in chronic hepatitis C, especially after categorizing the input dataset according to the activity or fibrosis degree in order to remove the interference between the fibrosis stage and necroinflammatory activity grade on texture features.     

Estimating the Clinical and Economic Benefit Associated with Incremental Improvements in Sustained Virologic Response in Chronic Hepatitis C

Introduction

Hepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40–80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR.

Methods

A published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies.

Results

QALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £300), increasing to £49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively.

Conclusion

Projecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.     

Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

Background/Aim

New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

Methods

To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.

Results

Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population) attend harm reduction (HR) programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap). The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.

Conclusions

Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.     

Hepatitis C Virus Epidemiology in Djibouti,Somalia, Sudan,and Yemen: Systematic Review and Meta-Analysis

Objectives

To characterize hepatitis C virus (HCV) epidemiology and assess country-specific population-level HCV prevalence in four countries in the Middle East and North Africa (MENA) region: Djibouti, Somalia, Sudan, and Yemen.

Methods

Reports of HCV prevalence were systematically reviewed as per PRISMA guidelines. Pooled HCV prevalence estimates in different risk populations were conducted when the number of measures per risk category was at least five.

Results

We identified 101 prevalence estimates. Pooled HCV antibody prevalence in the general population in Somalia, Sudan and Yemen was 0.9% (95% confidence interval [95%CI]: 0.3%–1.9%), 1.0% (95%CI: 0.3%–1.9%) and 1.9% (95%CI: 1.4%–2.6%), respectively. The only general population study from Djibouti reported a prevalence of 0.3% (CI: 0.2%–0.4%) in blood donors. In high-risk populations (e.g., haemodialysis and haemophilia patients), pooled HCV prevalence was 17.3% (95%CI: 8.6%–28.2%) in Sudan. In Yemen, three studies of haemodialysis patients reported HCV prevalence between 40.0%-62.7%. In intermediate-risk populations (e.g.. healthcare workers, in patients and men who have sex with men), pooled HCV prevalence was 1.7% (95%CI: 0.0%–4.9%) in Somalia and 0.6% (95%CI: 0.4%–0.8%) in Sudan.

Conclusion

National HCV prevalence in Yemen appears to be higher than in Djibouti, Somalia, and Sudan as well as most other MENA countries; but otherwise prevalence levels in this subregion are comparable to global levels. The high HCV prevalence in patients who have undergone clinical care appears to reflect ongoing transmission in clinical settings. HCV prevalence in people who inject drugs remains unknown.     

Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools,Hepatic Venous Pressure Gradient (HVPG) and Histology in Nonalcoholic Steatohepatitis

Background & Aims

Non-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology.

Methods

This was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan–Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC).

Results

During a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50).

Conclusions

Non-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.     

Soluble Adhesion Molecules in Patients Coinfected with HIV and HCV: A Predictor of Outcome

Background

Higher serum levels of adhesion molecules (sICAM-1 and sVCAM-1) are associated with advanced liver fibrosis in patients coinfected with human immunodeficiency virus and hepatitis C virus. We assessed the relationship between serum levels of adhesion molecules and liver-related events (LRE) or death, in coinfected patients.

Methods

We studied clinical characteristics and outcomes of 182 coinfected patients with a baseline liver biopsy (58 with advanced fibrosis) and simultaneous plasma samples who were followed for median of 9 years. We used receiver-operating characteristic (ROC) curves to calculate optimized cutoff values (OCV) of sICAM-1 and sVCAM-1, defined as the values with the highest combination of sensitivity and specificity for LRE. We used multivariate regression analysis to test the association between OCVs of sICAM-1 and sVCAM-1 and outcomes. The variables for adjustment were age, HIV transmission category, liver fibrosis, baseline CD4+ T-cell counts, antiretroviral therapy, and sustained virologic response (SVR).

Results

During the study period 51 patients had SVR, 19 had LRE, and 16 died. The OCVs for LRE were 5.68 Log pg/mL for sICAM-1 and 6.25 Log pg/mL for sVCAM-1, respectively. The adjusted subhazard ratio (aSHR) (95% confidence interval [CI]) of death or LRE, whichever occurred first, for sICAM-1 and sVCAM-1 > OCV were 3.98 ([1.14; 13.89], P = 0.030) and 2.81 ([1.10; 7.19], respectively (P = 0.030).

Conclusions

Serum levels of sICAM-1 and sVCAM-1 can serve as markers of outcome in HIV/HCV-coinfected patients. Therapies targeting necroinflammatory damage and fibrogenesis may have a role in the management chronic hepatitis C.     

Hemoglobin Decrease with Iron Deficiency Induced by Daclatasvir plus Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b

Background

Decreased hemoglobin (Hb) level has been supposed to be a relatively rare side effect of a combination therapy against hepatitis C virus that consists of the NS5A inhibitor daclatasvir (DCV) and the NS3/4A protease inhibitor asunaprevir (ASV).

Methods

The study was conducted in 75 patients with genotype 1b chronic hepatitis C virus infection who had started combination therapy with DCV and ASV at St. Marianna University School of Medicine Hospital between September 2014 and December 2014.

Results

Among the patients examined, decreased Hb level by ≥1.5 g/dL from the values at treatment initiation was observed in 11 individuals. This was accompanied by decreased mean corpuscular volume, and iron and ferritin levels.

Conclusions

These findings suggest that the mechanism of the phenomenon is caused by iron deficiency. The underlying mechanism and clinical impacts will need to be further examined.     

Reactivation of Hepatitis B Virus in HBsAg-Negative Patients with Hepatocellular Carcinoma

Background & Aims

Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE).

Methods

A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2–3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46).

Results

During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216–116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation.

Conclusions

TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.     

Age as a Predictor of Significant Fibrosis Features in HBeAg-Negative Chronic Hepatitis B Virus Infection with Persistently Normal Alanine Aminotransferase

Background

Although alanine aminotransferase (ALT) levels reflect the degree of liver damage, not all patients with chronic hepatitis B virus (HBV) infection exhibit persistently elevated ALT levels. In the present study, we aimed to comprehensively evaluate the characteristics of histological abnormalities in a large population of Chinese patients with chronic HBV and persistently normal ALT levels.

Methods

In total, 2303 consecutive patients who underwent liver biopsy were screened. Of these patients, 273 were categorized as having persistently normal ALT levels (PNALT), whereas 618 were categorized as having persistently or intermittently elevated ALT levels (PIALT). All these patients had at least three ALT values recorded in the year prior to the baseline liver biopsy.

Results

Significant necroinflammation was observed in 9.7% (11/113) patients with PNALT, 23.3% (42/180) patients with PIALT (ALT 1–2× upper limit of normal [ULN]), and 27.8% (42/151) patients with PIALT (ALT > 2× ULN), whereas significant fibrosis was observed in 8.8% (10/113) patients with PNALT, 27.8% (42/151) patients with PIALT (ALT 1–2× ULN), and 21.2% (32/151) patients with PIALT (ALT > 2× ULN). Multiple logistic regression analysis indicated that age parameters were associated with significant histological abnormalities in patients with PNALT. The area under the curve showed that age was associated with significant fibrosis characteristics in patients with hepatitis B extracellular antigen (HBeAg)-negative PNALT.

Conclusion

Significant histological abnormalities are not often observed in Chinese patients with PNALT. Interestingly, age appears to be a predictor of significant fibrosis in patients with HBeAg-negative PNALT.     

Profile of an HIV Testing and Counseling Unit in Bangladesh: Majority of New Diagnoses among Returning Migrant Workers and Spouses

Introduction

Analysis of data from HIV testing and counseling (HTC) services provides an opportunity to identify important populations for targeting of HIV prevention efforts. Our primary aim was to describe the demographics of clients presenting to HTC in Bangladesh, a low HIV prevalence country. Our secondary aim was to determine the risk factors for HIV positivity among returning migrant workers who were tested.

Methods

We performed a cross-sectional study of data collected between 2002 and 2010 from the first HTC service established in Bangladesh, located in three large cities.

Results

8973 individuals attended HTC services, with 558 (6.2%) of clients testing positive for HIV, including 33 children. The majority of those who tested positive were aged 25–44 (71%), male (70%), and married (68%). Key populations considered at increased risk of HIV, such as female sex workers, people who inject drugs, and males who have sex with males accounted for only 11% of adults who tested positive. Notably, 75% of adults testing positive had a history of migrant work or was the spouse of a migrant worker. In multivariable logistic regression of those with a migrant work history presenting for HTC, we found rural residence, working in the Middle East, and longer duration of migrant work to be independently associated with testing positive, and female gender and higher level of education to be negatively associated.

Conclusions

These data suggest that in Bangladesh, in addition to targeting traditional key populations, HIV prevention efforts should also focus on migrant workers and their spouses.     

Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis

Background and Aim

Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed.

Methods

The Medline, Web of Science, and Embase databases (from inception to June 2015) were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds ratios (ORs) of advanced hepatic fibrosis or cirrhosis for low or moderate, high, and any coffee consumption versus no consumption were pooled. Two cups per day was used as the cut-off level between low or moderate and high consumption.

Results

Sixteen studies were included, involving 3034 coffee consumers and 132076 people who do not consume coffee. The pooled results of the meta-analysis indicated that coffee consumers were less likely to develop cirrhosis compared with those who do not consume coffee, with a summary OR of 0.61 (95%CI: 0.45–0.84). For low or moderate coffee consumption versus no consumption, the pooled OR of hepatic cirrhosis was 0.66 (95%CI: 0.47–0.92). High coffee consumption could also significantly reduce the risk for hepatic cirrhosis when compared with no coffee consumption (OR = 0.53, 95%CI: 0.42–0.68). The effect of coffee consumption on hepatic fibrosis was summarized as well. The pooled OR of advanced hepatic fibrosis for coffee consumption versus no consumption was 0.73 (95%CI: 0.58–0.92). The protective effect of coffee on hepatic fibrosis and cirrhosis was also identified in subgroup meta-analyses of patients with alcoholic liver disease and chronic hepatitis C virus (HCV) infection.

Conclusion

Coffee consumption can significantly reduce the risk for hepatic fibrosis and cirrhosis.     

Loss from Treatment for Drug Resistant Tuberculosis: Risk Factors and Patient Outcomes in a Community-Based Program in Khayelitsha,South Africa

Background

A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting.

Methodology

LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013.

Results

Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment.

Conclusion

LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.     

Predictors of Frequent Emergency Room Visits among a Homeless Population

Background

Homelessness, HIV, and substance use are interwoven problems. Furthermore, homeless individuals are frequent users of emergency services. The main purpose of this study was to identify risk factors for frequent emergency room (ER) visits and to examine the effects of housing status and HIV serostatus on ER utilization. The second purpose was to identify risk factors for frequent ER visits in patients with a history of illicit drug use.

Methods

A retrospective analysis was performed on 412 patients enrolled in a Boston-based health care for the homeless program (HCH). This study population was selected as a 2:1 HIV seronegative versus HIV seropositive match based on age, sex, and housing status. A subgroup analysis was performed on 287 patients with history of illicit drug use. Chart data were analyzed to compare demographics, health characteristics, and health service utilization. Results were stratified by housing status. Logistic models using generalized estimating equations were used to predict frequent ER visits.

Results

In homeless patients, hepatitis C was the only predictor of frequent ER visits (OR 4.49, p<0.01). HIV seropositivity was not predictive of frequent ER visits. In patients with history of illicit drug use, mental health (OR 2.53, 95% CI 1.07–5.95) and hepatitis C (OR 2.85, 95% CI 1.37–5.93) were predictors of frequent ER use. HIV seropositivity did not predict ER use (OR 0.45, 95% CI 0.21 – 0.97).

Conclusions

In a HCH population, hepatitis C predicted frequent ER visits in homeless patients. HIV seropositivity did not predict frequent ER visits, likely because HIV seropositive HCH patients are engaged in care. In patients with history of illicit drug use, hepatitis C and mental health disorders predicted frequent ER visits. Supportive housing for patients with mental health disorders and hepatitis C may help prevent unnecessary ER visits in this population.     

Prediction of Week 4 Virological Response in Hepatitis C for Making Decision on Triple Therapy: The Optim Study

Background

Virological response to peginterferon + ribavirin (P+R) at week 4 can predict sustained virological response (SVR). While patients with rapid virological response (RVR) do not require triple therapy, patients with a decline <1log₁₀ IU/ml HCVRNA (D1L) should have treatment discontinued due to low SVR rate.

Aim

To develop a tool to predict first 4 weeks’ viral response in patients with hepatitis C genotype 1&4 treated with P+R.

Methods

In this prospective and multicenter study, HCV mono-infected (n=538) and HCV/HIV co-infected (n=186) patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model) and a validation cohort (to validate the model).

Results

D1L was reached in 509 (80.2%) and RVR in 148 (22.5%) patients. Multivariate analyses demonstrated that HIV co-infection, Forns’ index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC) for D1L was: 0.81 (95%CI: 0.76 — 0.86) in the estimation cohort and 0.71 (95%CI: 0.62 — 0.79) in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 — 0.88) in the estimation cohort and 0.82 (95%CI: 0.76 — 0.88) in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.

Conclusions

The combination of genetic (IL28B polymorphism) and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.     

Serum Osteopontin Predicts Degree of Hepatic Fibrosis and Serves as a Biomarker in Patients with Hepatitis C Virus Infection

Background & Aims

Osteopontin (OPN) is a matricellular protein that upregulates during pathogenesis of hepatic fibrosis. The present study was aimed to evaluate whether serum OPN could be used as a biomarker to assess the degree of hepatic fibrosis in patients with hepatitis C virus (HCV) infection.

Methods

Needle biopsy was performed on HCV patients and scored as zero fibrosis (F0), mild fibrosis (F1), moderate fibrosis (F2), severe fibrosis (F3) and liver cirrhosis (F4) based on Masson’s trichrome and α-smooth muscle actin (α-SMA) staining. Serum OPN levels were measured using ELISA and correlated with the degree of fibrosis. Furthermore, the OPN values were correlated and evaluated with platelets count, serum hyaluronic acid (HA), and collagen type IV and subjected to receiver operating characteristic (ROC) curve analysis.

Results

Serum OPN levels were remarkably increased from F0 through F4 in a progressive manner and the differences were significant (P < 0.001) between each group. The data were highly correlated with the degree of hepatic fibrosis. The ROC curve analysis depicted that serum OPN is an independent risk factor and an excellent biomarker and a prognostic index in HCV patients.

Conclusions

The results of the present study indicate that serum OPN levels reflect the degree of hepatic fibrosis and could be used as a biomarker to assess the stage of fibrosis in HCV patients which would help to reduce the number of liver biopsies. Furthermore, serum OPN serves as a prognostic index towards the progression of hepatic fibrosis to cirrhosis and hepatocellular carcinoma.