No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients.

BACKGROUND & AIMS: Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS: We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks. RESULTS: Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively (P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks' treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment. CONCLUSION: In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Comparing the Risk of Poor Outcomes Among Hepatitis C-Infected, Cured, and Never-Infected Controls.

Background and Aims: Studies show decreased rates of poor outcomes after hepatitis C virus (HCV) cure. However, there are no data comparing risk of poor outcomes to that of HCV never infected; results that could have implications for those who may not need ongoing specialty follow-up after cure. Methods: Retrospective cohort study conducted among Kaiser Permanente Northern California adults ages 18 and up between 2002 and 2019. Three cohorts were identified: 1) chronic HCV, 2) HCV cured, and 3) every chronic HCV and HCV-cured individual was matched by age, sex and race-ethnicity to 3 HCV negative controls. Outcomes of interest were cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and all-cause mortality. A low-risk group of HCV cured individuals without significant liver disease and/or concomitant liver disease cofactor(s) were identified. Results: We identified 21,184 chronic HCV, 11,950 HCV cure, and 99,402 control individuals. Five-year cumulative incidence of cirrhosis, decompensated cirrhosis, HCC and all-cause mortality was 10% vs 3.6% vs 0.8%, 12% vs 2.6% vs 0.6%, 3.9% vs 1.6% vs 0.07%, and 14% vs 2.8% vs 2.2% for chronic HCV, HCV cure, and control individuals, respectively (log-rank P < .01 for all). Compared to controls, HCV cured low-risk individuals had numerically similar 5-year cumulative incidence of cirrhosis, decompensated cirrhosis, HCC and all-cause mortality (1.2% vs 0.8%, P < .01; 0.9% vs 0.6%, P < .01; 0.5% vs 0.1%, P < .01; 1.7% vs 2.2%, P < .01). Conclusion: HCV cure provides significant health benefits but does not universally return risk of poor outcomes to that of the general population. A simple stratification at the time of HCV cure could identify low-risk individuals who can potentially be discharged from specialty clinics/HCC surveillance.

Hepatocellular Carcinoma in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Importance: In the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC. Objective: To develop a prediction model for HCC incidence in a cohort of patients with MASLD. Design, Setting, and Participants: This prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024. Exposure: Data were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD. Main Outcome and Measures: The cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk. Results: A total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241. Conclusions and Relevance: This prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.

Life Expectancy of Insured People With and Without Hepatitis C Virus Infection, 2007-2017.

Among 25 291 and 4 921 830 people with and without hepatitis C, life expectancy at age 20 increased 1.8 years and 0.3 years from the interferon to interferon-free era, respectively. Increases were highest for racial and/or ethnic minority groups with hepatitis C.

Hepatitis C treatment uptake and response among human immunodeficiency virus/hepatitis C virus-coinfected patients in a large integrated healthcare system.

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014-December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46-0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54-0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23-0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48-0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.

Disparities in Initiation of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in an Insured Population.

OBJECTIVES: The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. METHODS: We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. RESULTS: Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). CONCLUSIONS: Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.

Serum Fibrosis Marker Panels FIB-4 Index and Aspartate Aminotransferase (AST)-to-Platelet Ratio Index (APRI) Are Equivalent to AST Alone at Predicting Liver Fibrosis in a Cohort of 1731 Patients Infected with Hepatitis C Virus.

BACKGROUND: Efficient tools are needed to stage liver disease before treatment of patients infected with hepatitis C virus (HCV). Compared to biopsy, several studies demonstrated favorable performance of noninvasive multianalyte serum fibrosis marker panels [fibrosis-4 (FIB-4) index] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI), but suggested cutoffs vary widely. Our objective was to evaluate FIB-4 index and APRI and their component tests for staging fibrosis in our HCV-infected population and to determine practical cutoffs to help triage an influx of patients requiring treatment. METHODS: Transient elastography (TE) results from 1731 HCV-infected patients were mapped to an F0-F4 equivalent scale. Each patient's APRI and FIB-4 index were calculated. Areas under the receiver operator curve (AUROCs) and false-positive and false-negative rates were calculated to retrospectively compare the performance of the indices and their component tests. RESULTS: The highest AUROCs for distinguishing severe (F3-F4) from mild-to-moderate (F0-F2) fibrosis had overlapping 95% CIs: APRI (0.77; 0.74-0.79), FIB-4 index (0.76; 0.73-0.78), and AST (0.74; 0.72-0.77). Cutoffs had false-negative rates of 2.7%-2.8% and false-positive rates of 6.4%-7.4% for all 3 markers. CONCLUSIONS: AST was as effective as FIB-4 index and APRI at predicting fibrosis. Published cutoffs for APRI and FIB-4 index would have been inappropriate in our population, with false-negative rates as high as 11%. For our purposes, no serum fibrosis marker was sufficiently sensitive to rule-out significant fibrosis, but cutoffs developed for AST, FIB-4 index, and APRI all had specificities of 79.2%-80.3% for ruling-in severe fibrosis and could be used to triage 1/3 of our population for treatment without waiting for TE or liver biopsy.

Visualization of anterior chamber angle dynamics using optical coherence tomography.

PURPOSE: To describe the technology of optical coherence tomography (OCT) in imaging the anterior chamber angles and its impact on understanding the pathophysiology of angle-closure glaucoma (ACG). DESIGN: Observational case series. PARTICIPANTS: Three subjects with, respectively, impending angle-closure attack, plateau iris syndrome, and phacomorphic glaucoma were recruited. METHODS: The anterior chamber angle in each patient was imaged with a commercially available OCT unit. The angle configurations were assessed and compared before and after laser peripheral iridotomy (LPI) and argon laser peripheral iridoplasty (ALPI). MAIN OUTCOME MEASURES: Visualization of the changes in the anterior chamber angle configurations and normalization of the intraocular pressure (IOP). RESULTS: A patient with impending angle-closure attack precipitated by a topical mydriatic agent was treated with LPI. Optical coherence tomography imaging of the anterior chamber angles was performed before and after the laser procedure. Conversion of anterior iris bowing and angle crowding to iris straightening and angle opening after LPI was demonstrated. Intraocular pressure became normalized with the change in angle configuration. The second patient presented with symptoms of intermittent angle-closure attacks and was initially diagnosed with primary ACG. Despite successful LPI, the angles remained occludable, and the IOP continued to be elevated. Optical coherence tomography was used to review the anterior chamber angle configuration and demonstrated a typical pattern compatible with the diagnosis of plateau iris syndrome. Subsequent ALPI converted the plateau configuration to open angle, with normalization of IOP and disappearance of symptoms. The third patient presented with an acute angle-closure attack and was diagnosed with phacomorphic glaucoma. Argon laser peripheral iridoplasty was performed successfully to open the angle, as evident by the OCT images, and the IOP was brought under control, together with relief of symptoms. CONCLUSIONS: The commercially available OCT unit can be practically employed for anterior chamber angle imaging. The different patterns of angle configurations are correlated with the underlying pathophysiology in different forms of ACG.

Treatment of cystic epithelial downgrowth with intralesional administration of mitomycin C.

PURPOSE: To report a case of postoperative cystic epithelial downgrowth treated with needle aspiration and intralesional administration of mitomycin C. METHODS: Case report. A 60-year-old woman with a history of right cataract surgery 7 years ago presented with decreased vision of 1/60. The reduced vision was diagnosed secondary to a large acquired cystic epithelial downgrowth on the surface of the iris occluding the pupil. RESULTS: The cystic epithelial downgrowth was treated with aspiration and intralesional administration of mitomycin C solution. There was no evidence of recurrence on follow-up 1 year after the procedure. CONCLUSIONS: Treatment of acquired cystic epithelial downgrowth with needle aspiration and intralesional administration of mitomycin C resulted in a satisfactory outcome without undertaking more extensive and invasive surgical treatments.

Transmandibular, circumglossal, retropharyngeal approach for chordomas of the clivus and upper cervical spine. Technical note.

Extensive clival tumors that involve both the midline and lateral skull base compartments, or those that extend inferiorly to the anterior cervical spine, are difficult to expose in a wide fashion using any of the transmaxillary, transoral, or transcervical routes. In the transmandibular, circumglossal, retropharyngeal (TCR) approach wide access of this region can be obtained, thus allowing for a more complete resection of tumor and infiltrated bone. It also provides for an improved ability to perform dural reconstruction, should it be necessary. Over the past 4 years four patients with extensive clival chordomas underwent resection via the TCR approach. Gross-total resection was achieved in two patients, a greater than 98% resection in one patient, and a greater than 95% resection in the fourth patient. The surgical technique, all approach-related complications and morbidity, and patient outcome are discussed. If an expanded exposure of the clivus is necessary, the TCR approach is a good choice as well as a useful surgical technique to have available.

Localized conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is amenable to local chemotherapy.

PURPOSE: Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is a rare, low-grade, non-Hodgkin's B-cell lymphoma. We report our successful management of localized conjunctival MALT lymphoma with topical Mitomycin C (MMC). METHODS: This is a case report. A 35-year-old woman had a mobile painless 1.5x1-cm mass in the left conjunctiva for 2 years. Examination revealed two similar masses in the right conjunctiva. Incisional biopsy for immunohistochemical stain and PCR of the left conjunctival mass showed MALT lymphoma. She was given four courses of topical 0.04% MMC eyedrops. There was transient conjunctival injection and superficial punctate keratopathy which responded to topical steroid and lubricant. RESULTS: The lesions regressed completely after the fourth cycle of treatment and repeat biopsy confirmed complete remission. CONCLUSION: This is the first report of localized conjunctival MALT lymphoma being successfully treated by topical MMC with minimal local controllable side effects.