A Prospective Open-Label Dose-Response Study to Correct Vitamin D Deficiency in Cirrhosis.

BACKGROUND: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown. OBJECTIVE: We aimed to establish the dose-response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis. DESIGN: An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose-response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE). RESULTS: Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01). CONCLUSIONS: A two-tiered dosing regimen of daily oral vitamin D3 supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use.

Real-World Sustained Virologic Response Rates of Sofosbuvir-Containing Regimens in Patients Coinfected With Hepatitis C and HIV.

BACKGROUND: Patients with hepatitis C virus (HCV) with or without human immunodeficiency virus (HIV) achieve high sustained virological response (SVR) rates on sofosbuvir (SOF)-containing regimens in clinical trials. Real world data on patients coinfected with HCV and HIV treated with SOF-based regimens are lacking. METHODS: This observational cohort study included HIV/HCV-coinfected adults with genotype 1 HCV who initiated treatment with a SOF-containing regimen between December 2013 and December 2014 (n = 89) at the Mount Sinai Hospital or the Brooklyn Hospital Center. The primary outcome was SVR at 12 weeks after the end of treatment. The secondary outcomes were risk factors for treatment failure, serious adverse events, and side effects. A post hoc per protocol analysis of SVR was performed on patients who completed treatment and follow-up. RESULTS: In an intention-to-treat analysis, SVR rates were 76% (31/41) for simeprevir (SMV)/SOF, 94% (16/17) for SMV/SOF/ribavirin (RBV), and 52% (16/31) for SOF/RBV. The SVR rates of SMV/SOF/RBV and SMV/SOF did not differ significantly in this small study (P = .15). However the SVR rate of SMV/SOF/RBV was higher than that of SOF/RBV (P < .01). In a per protocol analysis, SMV/SOF/RBV had a higher SVR rate than SOF/RBV: 100% (16/16) vs 57% (16/28) (P < .01). The most commonly reported adverse effects were rash, pruritus, fatigue, and insomnia. One patient who had decompensated cirrhosis prior to treatment initiation died after receiving SMV/SOF. CONCLUSIONS: SMV/SOF ± RBV is an effective option with minimal adverse effects for most HIV-positive patients with genotype 1 HCV. SMV should be used with caution in patients with decompensated cirrhosis.

A Novel Collaborative Community-Based Hepatitis B Screening and Linkage to Care Program for African Immigrants.

BACKGROUND: Sub-Saharan African nations have among the highest rates of chronic hepatitis B virus (HBV) infection worldwide, but little is known about HBV infection in African-born persons in the United States. METHODS: From October 2011 to July 2013, community-based HBV screenings were conducted targeting persons originating from Africa in New York City. Persons were identified as currently HBV infected (HBsAg positive) or exposed (HBcAb positive). RESULTS: Overall, 955 persons were screened for HBV; the median age was 45 years (interquartile range, 35-54 years) and 75.5% were men. Of these, 919 persons had no history of liver disease, of whom 9.6% (n = 88) had current HBV infection and 73.9% (n = 679) had exposure. In logistic regression, older age (odds ratio [OR], 0.97; 95% confidence interval [CI], .94-.99; P < .01) and female sex (OR, 0.35; 95% CI, .14-.75; P < .01) were less likely to be associated with HBV infection, whereas having a mother with hepatitis was associated with infection (OR, 18.8; 95% CI, 2.72-164.65; P < .01). HBV exposure was associated with older age (OR, 1.03; 95% CI, 1.01-1.04; P < .01), whereas female sex (OR, 0.46; 95% CI, .33-.66; P < .01) and history of blood transfusion (OR, 0.43; 95% CI, .22-.83; P = .01) were negatively associated. A patient navigator linked 97% of infected persons to care. Eleven persons were recommended for treatment, of whom 9 (82%) started therapy. Three persons were diagnosed with hepatocellular carcinoma on the first screening ultrasound. CONCLUSIONS: The high burden of HBV infection among African immigrants in the United States underscores a need for continued screening and linkage to care in this at-risk population.

Low adherence of HIV providers to practice guidelines for hepatocellular carcinoma screening in HIV/hepatitis B coinfection.

BACKGROUND: In the era of combination therapy for human immunodeficiency virus (HIV), liver disease, and hepatocellular carcinoma (HCC) are major causes of death for patients coinfected with HIV and hepatitis B virus (HBV). This study compared HIV provider and hepatologist awareness of and adherence to the American Association for the Study of Liver Diseases (AASLD) practice guidelines for chronic HBV management. The primary endpoint of HIV provider adherence to HCC screening recommendations was compared to that of hepatologists at a large metropolitan academic medical center. METHODS: Medical record database searches by ICD-9 codes were used to identify HIV/HBV coinfected (n = 144) and HBV monoinfected (n = 225) patients who were seen at least twice over a 2-year period in outpatient clinics. Adherence to AASLD guidelines was assessed by chart review. Provider awareness was evaluated through a voluntary anonymous survey with knowledge-based questions. RESULTS: Over a 2-year period, only 36.0% of HIV/HBV coinfected patients seen in HIV practices completed HCC screening compared to 81.8% of HBV monoinfected patients in hepatology practices (P < .00001). Similarly, HIV providers less frequently monitored HBV viral load (P < .0001), HBeAg/anti-HBe (P < .00001), HBsAg/anti-HBs (P < .00001) than hepatologists but screened more often for hepatitis A immunity (P = .028). Self-reported adherence and knowledge scores were similar among 19 HIV providers and 16 hepatologists. CONCLUSIONS: HIV providers ordered significantly fewer HCC screening and HBV monitoring tests than hepatologists within a single academic medical center. In the setting of increased reliance on quality indicators for care, both patients and providers will benefit from greater adherence to established guidelines.

Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response.

UNLABELLED: In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). CONCLUSIONS: TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR.

Diabetes mellitus and advanced liver fibrosis are risk factors for severe anaemia during telaprevir-based triple therapy.

BACKGROUND & AIMS: Adding telaprevir to pegylated-interferon and ribavirin increased both response rates and side effects of hepatitis C virus (HCV) treatment. We identified variables associated with severe anaemia during telaprevir-based triple therapy. METHODS: An observational study was performed on 142 HCV-infected patients between June 2011 and March 2012. All subjects completed 12 weeks of telaprevir-based triple therapy or discontinued early because of anaemia. Severe anaemia was defined by a haemoglobin≤8.9 g/dl; advanced fibrosis was determined by Fib-4≥3.25. RESULTS: The 47 (33%) patients who developed severe anaemia were similar to those who did not in sex, race, and prior response to dual therapy, but they were more likely to have diabetes (23.4% vs. 6.3%, P<0.01), advanced fibrosis (46.8% vs. 29.5%, P=0.04) and a history of anaemia during previous dual therapy (29.7% vs. 11.4%, P=0.02). Patients developing severe anaemia were older (59 vs. 56 years, P=0.02), had lower baseline platelet counts (134 vs. 163×10(9) /L, P=0.04), haemoglobin (14.0 vs. 15.0 g/dl, P<0.01), estimated glomerular filtration rate (79 vs. 90 ml/min/1.73 m2, P=0.03) and a higher median ribavirin/weight ratio (14.9 vs. 13.2 mg/kg, P<0.01). In multivariable logistic regression, presence of diabetes (OR=5.61, 95% CI: 1.59-19.72), Fib-4≥3.25 (OR=3.09, 95% CI: 1.28-7.46), higher ribavirin/weight ratio (OR=1.31 per mg/kg, 95% CI: 1.13-1.52) and lower baseline haemoglobin (OR=0.57 per g/dl, 95% CI, 0.41-0.80) were independently associated with developing severe anaemia. CONCLUSIONS: Severe anaemia occurred in one-third of patients receiving telaprevir-based triple therapy. Risk was greater in patients with diabetes, advanced liver fibrosis, higher ribavirin/weight ratio and lower baseline haemoglobin.

HIV-hepatitis C virus co-infection in the era of direct-acting antivirals.

Approximately one-third of patients infected with human immunodeficiency virus (HIV) are concomitantly infected with hepatitis C virus (HCV). As a result, liver disease remains a major source of morbidity and mortality in HIV patients. Prior to 2011, treatments of HCV lacked efficacy in clinical trials in HIV/HCV co-infected patients. Fortunately, several direct-acting antivirals (DAAs) have now entered clinical practice and others have reached advanced stages of clinical development. These therapies offer significant benefits such as improved rates of sustained virologic response (SVR), shortened durations of treatment, and compatibility with HIV antiretroviral therapies. Treatments such as sofosbuvir (SOF) have received approval for HIV/HCV co-infected patients. Moreover, interferon-free options exist for HIV/HCV co-infected patients who may be ineligible or intolerant of interferon. Despite these improvements, physicians must be aware of the differences between these DAAs, the patient characteristics that play a role on the effectiveness of these medications, and the drug-drug interactions these DAAs may have with existing HIV antiretroviral therapies. The aim of this review is to discuss the prevalence and incidence of HIV/HCV co-infection, critical factors related to patient evaluation, current treatment options, and new developments in the management of HIV/HCV co-infected patients.

Hepatitis C direct-acting antiviral agents: changing the paradigm of hepatitis C treatment in HIV-infected patients.

Hepatitis C virus (HCV)-related liver disease is a major source of mortality in HIV-infected patients. Approximately one third of all patients with HIV are co-infected with HCV. Patients co-infected with HIV/HCV have shown lower rates of sustained virologic response with pegylated-interferon and weight-based ribavirin as well as more rapid progression of fibrosis than those with HCV mono-infection. Several direct-acting antiviral agents (DAAs), developed originally for HCV mono-infection, are being reevaluated for HIV/HCV co-infection. In addition, entirely new DAAs are being developed, including, interferon-free regimens with fewer side effects, allowing novel treatment opportunities for difficult-to-treat patients. In order for HCV DAAs to be successfully used in the HIV/HCV co-infected population several hurdles must be overcome, including adverse event management and drug-drug interactions. The aim of this review is to discuss the results of trials for new HCV therapies being developed for HIV/HCV co-infected patients and the impact of interferon-free regimens on treatment in the future.

MELD score and antibiotics use are predictors of length of stay in patients hospitalized with hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) represents a significant burden to the healthcare system. The aim of this study was to determine factors influencing the hospital length of stay among patients hospitalized with HE. METHODS: A data warehouse query was performed to identify 316 patients with a first hospitalization during which HE occurred, between April 2010 and February 2012. Baseline and hospitalization characteristics were collected with IRB approval. A negative binomial multivariable model was used to control for potential confounders on the length of hospitalization. RESULTS: Median age was 59 years, and 60.4% of admitted patients were male. The median MELD score was 22 (IQR: 17-28). Median length of stay was 8 days (IQR: 3.25-14.25). After controlling for MELD score, female gender (2.2 days; p = 0.04), being initially admitted for a reason other than HE (liver-related: 7.6 days; p < 0.01 and non liver-related 10.7 days; p < 0.01) and receiving antibiotics other than rifaximin (10.5 days; p < 0.01) were associated with longer length of stay whereas hepatitis C (-3.1 days; p < 0.01) was associated with a shorter length of stay. CONCLUSIONS: MELD score, gender, use of antibiotics other than rifaximin, reason for admission and hepatitis C are predictors readily available in clinic that can help identify patients at risk for longer length of stay.

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis.

BACKGROUND: Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). AIMS: To identify risk factors for new-onset HCC in patients cured of hepatitis C. METHODS: Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post-SVR HCC were identified by comparison with HALT-C participants who did not develop post-SVR HCC. RESULTS: Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post-SVR [interquartile range (IQR) =1.4-10y] at a median age of 61 years (IQR, 59-67). Approximately one-third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25-4), indicating mild necroinflammation. In a multivariable logistic regression model, post-SVR HCC was positively associated with non-Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/µL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. CONCLUSIONS: One-third of patients with post-SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post-SVR HCC risk.

Real-world experience of treating frozen shoulder using active manipulation under local anesthetic: A retrospective study.

ABSTRACT: Currently, there is limited evidence to guide treatment and no standard management guidelines exist for treating frozen shoulder (FS). A general management approach consists of initial evaluation, range of motion (ROM) exercises, intra-articular injection of glucocorticoid, home exercise program (HEP), and/or physical therapies. However, the general approach lacks detail and has limited evidence of its effectiveness. This retrospective cohort study evaluates the short-term recovery of near-full to full-ROM technique followed by an instructed HEP for strengthening and coordinating shoulder girdle muscle group for FS management. This study details our experiences following a general approach to managing FS and aims to fill this knowledge void, providing additional context of the efficacy of FS management in the real-world. Seven-two adult patients with FS (46 females, 26 males; mean age of 66; standard deviation of 15.1; range 23-87) from an orthopedic and physical medicine and sport medicine office between 2014 and 2018 were included in this study. Following general management of FS, patients received a glucocorticoid-lidocaine mixture injection administered to the respective shoulder at the glenohumeral joint space and/or subacromial separately. Immediately, patients underwent active manipulation of the affected shoulder in 3 directions: forward flexion, abduction, and extension in the sagittal plane. Lastly, patients were instructed to perform movements similar to the active manipulation protocol as a HEP. The abduction and forward flexion ROM showed significant improvements with the described protocol. Following treatment, there was a 90.20° and 77.33° increase in average shoulder abduction and forward flexion ROM, respectively (P < .05). The immediate goal of this protocol was to gain maximum ROM in different directions of shoulder mobility. Following the general management of FS, active manipulation under local anesthetic was a highly effective treatment modality for adhesive capsulitis that was time-saving and cost-effective.

Real World Experience of Drug Induced Liver Injury in Patients Undergoing Chemotherapy.

BACKGROUND & AIM: To better understand the clinical significance of drug induced liver injury (DILI) during chemotherapy, we examined the epidemiology, incidence, and treatment effects of DILI in patients undergoing chemotherapy for genitourinary malignancies over a two-year period. METHODS: We conducted a retrospective review of 284 patients who underwent chemotherapy for prostate, bladder, testicular and renal cell carcinomas over a two year period. Those with abnormal or absent liver test (LT) results prior to chemotherapy initiation were excluded. Post chemotherapy LT results were defined as DILI if ALT>3× ULN and/or total bilirubin (TB)>2× ULN, in the absence of other more likely causes of elevated LT. RESULTS: The cumulative incidence of DILI in the total study population was 6.1% (17/284), and in the population who had appropriate LT performed it increased to 18.9% (17/90). Chemotherapeutic agents were determined to be the cause of DILI in 82% (14/17) of patients, and the treatment plans were changed in 59% (10/17) of patients. CONCLUSION: In this real world study, the cumulative incidence of DILI was higher than commonly reported in clinical trials, and the majority of affected patients had to have their cancer treatment altered or interrupted.

Factors associated with success of telaprevir- and boceprevir-based triple therapy for hepatitis C virus infection.

AIM: To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODS: Outcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTS: The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 104 cells/µL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/µL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION: The SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results.

AIM: To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. METHODS: The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response - the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response (SVR) 12] - were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression. RESULTS: SVR12 rates were as follows: 86% (95%CI: 80%-91%) among 178 patients on SMV/SOF ± RBV; 62% (95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78% (95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR12 were $174442 (standard deviation: ± $18588) for SMV/SOF ± RBV; $223003 (± $77946) for SOF/RBV; and $126496 (± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio (OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin (OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR12 (OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION: SVR12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus.

BACKGROUND AND AIM: To investigate the impact of a sustained virological response (SVR) to hepatitis C virus (HCV) treatment on liver stiffness (LS). METHODS: LS, measured by transient elastography (FibroScan), demographic and laboratory data of patients treated with interferon (IFN)-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment) were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant. RESULTS: The median age of the patients (n = 100) was 60 years [IQR (interquartile range) 54-64); 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25-18.60) pre-treatment to 7.60 kPa (IQR: 5.60-12.38) at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60%) of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 --0.38) versus -2.40 kPa (IQR: -7.70 --0.23), p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98-0.5) during a median follow-up time of 1.17 (IQR: 0.88-1.63) years, which was not a statistically significant decrease (p = 0.99). CONCLUSIONS: LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.

Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus.

AIM: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection. METHODS: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome. RESULTS: Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m(2), 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases. CONCLUSION: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

Re-re-treatment of hepatitis C virus: Eight patients who relapsed twice after direct-acting-antiviral drugs.

AIM: To determine risk factors associated with hepatitis C virus (HCV) treatment failure after direct acting antivirals in patients with complex treatment histories. METHODS: All HCV mono-infected patients who received treatment at our institution were queried. Analysis was restricted to patients who previously failed treatment with boceprevir (BOC) or telaprevir (TVR) and started simeprevir (SMV) and sofosbuvir (SOF) ± ribavirin (RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus (HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December, 31(st) 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics, HCV infection, and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF. RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon (PEG) and RBV who failed this triple therapy were subsequently re-treated with an off-label all-oral regimen of SMV and SOF for 12 wk, with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response, but later relapsed. Eight (100%) patients were male. Mean age was 56 (range, 49-64). Eight (100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6 (mean 3.8). Eight (100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven (87.5%) patients had genotype 1a HCV. Seven (87.5%) patients had over 1 million IU/mL HCV RNA at the time of re-treatment. CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.

Primary Care-Based Hepatitis C Treatment Outcomes With First-Generation Direct-Acting Agents.

OBJECTIVES: Vulnerable, urban populations with a history of substance use disorders have a high prevalence of hepatitis C virus (HCV). Primary care-based treatment has been proposed to improve access to care. In this study, we present outcomes from our urban, primary care-based HCV treatment program in patients treated with telaprevir or boceprevir in combination with pegylated-interferon and ribavirin ("triple therapy"). METHODS: We collected data from 126 consecutive patients with genotype 1 HCV monoinfection seen in our treatment program (2011-2013). Among the 40 who initiated treatment, we analyzed factors associated with achieving a sustained viral response (SVR). RESULTS: During the study period, 40 patients initiated triple therapy (32%), 80% with recent or past substance use disorders. Patients initiating treatment were younger than untreated patients (P = 0.002), but otherwise did not differ demographically, or in the severity of their liver fibrosis (P > 0.05). An SVR was achieved in 18 patients (45%) and was less likely in patients with recent or past substance use disorders or psychiatric illness (both P < 0.01). CONCLUSIONS: Nearly one third of patients initiated triple therapy with SVR rates comparable to other HCV treatment settings, despite a significant burden of mental illness and substance dependence. Our experience demonstrates that a primary care-based practice can successfully deliver HCV care to a vulnerable population. Additional interventions may be needed to improve outcomes in patients with recent or past substance use disorders or psychiatric illness.

Pegylated-IFNα2a for HIV/hepatitis C virus coinfected patients: out with the old, in with the new.

INTRODUCTION: Liver disease is a major burden in patients co-infected with HIV and hepatitis C virus (HCV). From the time of its approval, pegylated-IFNα-2a (pegIFN-α2a) has played a major role in treatment of HCV in HIV/HCV co-infection. AREAS COVERED: This article briefly summarizes the epidemiology of HCV/HIV co-infection, the pharmacokinetic, and pharmacodynamic properties of pegIFN-α2a. Results from clinical trials investigating therapies containing pegIFN-α2a for HIV/HCV co-infected patients will be discussed with a focus on efficacy and safety. EXPERT OPINION: PegIFN-α2a has improved rates of sustained virologic response for co-infected patients. In combination with direct-acting antivirals (DAA), the disparity between mono- and co-infected patients is beginning to disappear. For the first time, IFN-free regimens are available in clinical practice. It is unlikely that pegIFN-α2a will continue to be a critical component in treatments for HCV in the general co-infected population.