Mild Liver Disease Research Articles

Unraveling the Mechanisms of MicroRNA in Suppressing Hepatitis B Virus Progression: A Comprehensive Review for Designing Treatment Strategies

: Liver cancer and cirrhosis caused by the Hepatitis B virus (HBV) remain significant global health challenges due to the virus's high prevalence and contagious nature. Hepatitis B virus can be transmitted through various means, leading to mild or severe liver disease. Although an effective prophylactic vaccine is available, it offers limited benefits for those already chronically infected. Current treatments often fail to consistently eliminate the virus and can cause severe adverse effects. In response to these challenges, researchers have begun exploring microRNAs (miRNAs) as novel therapeutic targets. Studying miRNA-virus interactions presents a promising opportunity to identify potential therapeutic targets. By manipulating host miRNAs, researchers aim to enhance antiviral defenses, restore cellular balance, and prevent viral replication. The text concludes by highlighting the potential for personalized medicine in Hepatitis B treatment, guided by individual miRNA profiles. Numerous studies have been conducted to understand how different miRNAs inhibit HBV replication, paving the way for the development of innovative and effective therapeutic strategies.

High comorbidity burden and low incidence of adverse events in primary shoulder arthroplasty in tertiary care at a university hospital

BackgroundReducing perioperative risk is in the focus of primary arthroplasty caregivers. Primary shoulder arthroplasty patients are considered among those with the lowest perioperative risk. Nonetheless, in tertiary care centres and university settings patients with significant comorbidities are being treated. It remains unclear whether the overall comorbidity burden is truly higher and if this results in an increased frequency of adverse events (AE). As a result, we conducted a study to assess the comorbidity burden and the frequency of major perioperative adverse events and predictive factors following primary shoulder arthroplasty in the university setting. MethodsA retrospective cohort analysis was conducted on patients undergoing primary shoulder arthroplasty for a non-trauma, non-tumour indication from January 1st, 2014 through December 31st, 2018. Administrative data were recorded to assess comorbidity burden and revision surgery within the first postoperative year. Major adverse events were routinely recorded on a weekly basis by the treating physicians. Descriptive and comparative statistical analyses were performed. The cohort was compared against a large North American sample. ResultsOf 386 patients who underwent 400 primary shoulder arthroplasties 14 (3.5 %) experienced adverse events. While AE were distributed equally among anatomical and reverse shoulder arthroplasties, no adverse event was recorded in the 34 hemiarthroplasty patients. The cohort showed an increased comorbidity burden in international comparison. Peptic ulcer disease was significantly associated with AE, while mild liver disease experienced a trend towards AE. ConclusionWe found an increased comorbidity burden and a low rate of AE for primary shoulder arthroplasty in a tertiary care and university setting. The distinct role of peptic ulcer disease in this cohort and the trend in mild liver disease merit further investigation in larger samples. The findings underscore the importance of perioperative risk assessment and management. Level of evidenceIII, retrospective cohort study.

Risk of mortality among patients with alcohol-associated hepatitis in the US from 2007 to 2021

Background/AimsAlcohol-associated hepatitis (AH) mortality and risk factors have not been carefully studied in real-world settings. We examined the rate, temporal trend, and risk factors of mortality in AH. MethodsWe conducted a cohort study of individuals with AH diagnoses using medical claims data from Optum's Clinformatics® Data Mart (CDM). Participants were individuals covered by Medicare Advantage and commercial insurance policies. Cases were identified using diagnostic codes. Cox regressions were used to estimate 90 and 180-day mortality rates by hospitalization status. ResultsThe cohort included 32,001 patients (72% men) who had at least one year of continuous insurance coverage prior to AH diagnoses. Of these, 20,912 were hospitalized within seven days of diagnosis. Ninety and 180-day mortality rates were 12.0% (95% CI [11.6%, 12.5%]) and 16.0% (95% CI [15.4%, 16.5%]), respectively, for the hospitalized patients and 3.1% (95% CI [2.8%, 3.4%]) and 5.1% (95% CI [4.6%, 5.5%]) for the non-hospitalized patients. Pre-existing liver disease, even in a mild form, was associated with an increased risk of death. In hospitalized patients, a history of mild liver disease was associated with a 24% increase in 180-day mortality risk (HR = 1.24, 95% CI: [1.14, 1.36]). Moderate-to-severe liver disease was associated with a more than doubled risk (HR = 2.33, 95% CI: [2.12, 2.56]). ConclusionsHistory of liver disease was associated with significantly increased AH mortality. The finding highlights the chronic disease context of AH and suggests that prior diagnosis of liver disease should be considered for prognosis and targeted prevention.

Epidemiology of Hepatocellular Carcinoma in Taiwan.

Hepatocellular carcinoma (HCC) is a major contributor to the world's cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013-2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77-83.01% with mild liver disease and 29.93-37.30% with diabetes (without complications) in the period 2013-2021. The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.

Real-world utilization patterns of radium-223 in metastatic prostate cancer in the United States: An administrative claims database study.

79 Background: Radium (Ra)-223 is approved for use in men with symptomatic castration resistant prostate cancer (CRPC) with bone metastases, demonstrating benefits in terms of overall survival and quality of life with a reliable safety profile. In the rapidly evolving treatment landscape for prostate cancer, real-world (RW) data on Ra-223 utilization are limited. We aimed to examine the RW utilization patterns of Ra-223 in patients with metastatic prostate cancer using a large administrative claims database in the US. Methods: A retrospective cohort of men treated with Ra-223 was identified using the closed claims private payor database of the Komodo Research Dataset covering the period from 01/01/2017 to 06/30/2022. The earliest administration of Ra-223 in men with bone metastatic prostate cancer was considered as index date. Individuals were required to have continuous insurance coverage at least 12-month pre-index (baseline) and least 6-month post index or until death if patients survived < 6 months (follow-up). Logistic regression was used to identify baseline demographic, clinical, medications, or healthcare resource use-related factors associated with receiving 5+ cycles of Ra-223. Results: The study cohort comprised of 1,376 men with a median age of 68 years at the time of Ra-223 initiation. Most men were treated by oncologists (52.2%), having bone only metastases (51.5%), having Charlson comorbidity index (CCI) ≥ 1 (76.2%). Diabetes (34.1%), peripheral vascular disease (29.9%), pulmonary disease (25.9%) and mild liver disease (25.1%) were the most common pre-existing comorbidities. Therapies received prior to Ra-223 were androgen receptor pathway inhibitors (75.4%), chemotherapy (32.1%), sipuleucel-T (13.7%) and bone health agents (73.7%). Ra-223 was utilized as a combination therapy by 26.0% of the overall population, predominately with enzalutamide. Nearly 15%, 38%, and 31% received Ra-223 (mono or combination therapy) as 1st, 2nd, and 3rd line therapy, respectively. Approximately 46% of the overall cohort and 54% of those who survived ≥ 6 months had received 5+ cycles, respectively. In regression analysis, men with short survival (<6 month) [Odds ratio, OR: 0.05, 95% confidence interval (CI): 0.03, 0.10], low CCI (0 vs. 4+) (OR: 0.38, 95% CI:0.19, 0.76), and pulmonary disease (OR: 0.71, 95% CI: 0.52, 0.97) had lower likelihood of completion of 5+ cycles. Conclusions: Nearly half of men completed 5+ cycles of Ra-223 therapy in a large US cohort of relatively young mCRPC men with private health insurance. Advanced disease state with short survival and low comorbidity were key factors associated with lower completion of 5+ cycles. The findings highlight the importance of utilizing Ra-223 early after mCRPC diagnosis, when the probability of >6-month survival is higher, to enhance treatment completion that has been shown to result in better outcomes.

Microemulsion co-delivering curcumin and DHA-rich algal oil alleviates nonalcoholic fatty liver disease

The combined effect of curcumin and docosahexaenoic acid (DHA) on liver injury has not yet been reported. We determined the synergistic effect of curcumin and DHA on the protection of WRL-68 cells from palmitic acid-induced injury, and on the inhibition of LX2 cells. A microemulsion to co-deliver both compounds was prepared by ultrasonic emulsification. Mice were fed a high-fat diet for 10 weeks to induce mild non-alcoholic fatty liver disease (NAFLD). At a dose of 5 mg/kg curcumin and 30 mg/kg DHA, the microemulsion successfully lowered serum triacylglycerol (TG) and low-density lipoprotein cholesterol levels, and significantly attenuated NAFLD. A pharmacokinetic study in rats showed that the microemulsion had a higher Cmax value for curcumin, a greater AUC0–24 value and a longer t1/2 value for both curcumin and DHA. This investigation provides a novel application of a combination of functional food ingredients to treat chronic liver disease.

Steatotic liver disease is the most important somatic determinant of quality of life in patients with obesity: A cross-sectional study.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are often comorbid and stigmatized. This can negatively affect quality of life (QOL). Other studies have primarily used the Chronic Liver Disease Questionnaire (CLDQ), which focuses on liver-related symptoms, to characterize QOL, but most MASLD patients have only mild liver disease, and CLDQ might overlook QOL issues pertaining to them. We aimed to determine the impact of metabolic dysfunction-associated steatohepatitis (MASH) on QOL in obese patients using a 136-item generic QOL questionnaire. We included participants with BMI ≥ 35 kg/m2 who all fully answered the sickness impact profile (SIP, range 0-100, normal = 3.4, 100 = worst) and had a liver biopsy to diagnose MASLD. Sociodemographics, comorbidity and biometric data were obtained from all participants. Of 176 (mean age 45.9 years, 70% female, 12.6 years of education), 132 had no-MASH and 44 MASH. On stepwise multivariable regression analysis, divorce (p = .011), unemployment (p < .003) and hepatic steatosis (p = .01) were associated with poor overall QOL. No other somatic comorbidity was associated. MASH patients more frequently than no-MASH reported physical discomfort (48% vs. 30%, p = .04), inability to do daily activities (29% vs. 54%, p = .006) and attention problems (32% vs. 57%, p = .003). MASLD severity was the only somatic determinant of QOL in patients with obesity in this cohort, and a large fraction reported debilitating symptoms. Patients and caregivers should consider the limitations this poses when planning interventions.

Incidentally Discovered Cryptogenic Cirrhosis in a Patient with Untreated Celiac Disease

Celiac disease is a common gastrointestinal disorder that primarily manifests its effects on the small bowel. However, the systemic nature of this condition, especially regarding the liver, has been gaining some recognition in the literature. Mild liver disease is common, but few cases progress to cirrhosis. We present a case of an asymptomatic 78-year-old male with a past medical history of longstanding celiac disease, atrial fibrillation, heart failure with preserved ejection fraction, type 2 diabetes mellitus (DM), and chronic kidney disease stage III who underwent a computed tomography (CT) scan for thoracic aortic aneurysm surveillance. Incidentally, on a CT scan, cirrhotic liver morphology was discovered. Right upper quadrant ultrasound confirmed heterogenous echotexture of the liver, consistent with a diagnosis of cirrhosis. Laboratory work-up demonstrated elevated alkaline phosphatase of 171, tissue transglutaminase (TTG) significantly elevated at &gt; 100, and a negative panel of other chronic liver disease labs, including negative anti-smooth muscle antibody, antimitochondrial antibody, liver kidney microsomal antibody, HFE gene, ceruloplasmin, alpha-1-antitrypsin, and alpha-fetoprotein &lt; 2 ng/mL. The patient was not taking any hepatotoxic medications. Although the patient did have type 2 DM, his hemoglobin A1c was well-controlled at 5.9%, and he had no hyperlipidemia and a normal body mass index, making a metabolic etiology of liver disease less likely. The patient had no significant alcohol use, either. The only patient’s major risk factor for liver disease was his untreated celiac disease, diagnosed in infancy. The patient was instructed to avoid any gluten, alcohol, and other hepatotoxic substances and was subsequently followed by a gastroenterologist. The following case report explores the pathogenesis of celiac-associated liver disease and the effect a gluten-free diet can have on the small bowel and the liver.

Hepatitis C Virus (HCV) Infection and Neurocognitive Impairment in Subjects with Mild Liver Disease.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related deaths. It is estimated that 40-74% of patients with hepatitis C will experience at least one extrahepatic manifestation within their lifetime. The finding of HCV-RNA sequences in post-mortem brain tissue raises the possibility that HCV infection may affect the central nervous system and be the source of subtle neuropsychological symptoms, even in non-cirrhotic. Our investigation aimed to evaluate whether asymptomatic, HCV-infected subjects showed cognitive dysfunctions. Twenty-eight untreated asymptomatic HCV subjects and 18 healthy controls were tested using three neuropsychological instruments in a random sequence: Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Continuous Visual Attention Test (CVAT). We performed depression screening, liver fibrosis assessment, blood tests, genotyping, and HCV-RNA viral load. A MANCOVA and univariate ANCOVAS were performed to examine group differences (HCV vs. healthy controls) in four scores of the CVAT (omission errors, commission errors, reaction time-RT, and variability of RT-VRT), and the scores derived from the SDMT, and the COWAT. A discriminant analysis was performed to identify which test variables effectively discriminate HCV-infected subjects from healthy controls. There were no group differences in the scores of the COWAT, SDMT, and in two variables of the CVAT (omission and commission errors). In contrast, the performance of the HCV group was poorer than the controls in RT (p = 0.047) and VRT (p = 0.046). The discriminant analysis further indicated that the RT was the most reliable variable to discriminate the two groups with an accuracy of 71.7%. The higher RT exhibited by the HCV group may reflect deficits in the intrinsic-alertness attention subdomain. As the RT variable was found to be the best discriminator between HCV patients and controls, we suggest that intrinsic-alertness deficits in HCV patients may affect the stability of response times increasing VRT and leading to significant lapses in attention. In conclusion, HCV subjects with mild disease showed deficits in RT and intraindividual VRT as compared to healthy controls.

Ethnic disparity in hospitalization among veterans with COVID-19 and cancer.

e18613 Background: COVID19 results in severe disease and resource utilization, particularly among patients with cancer. Hospitalization rates among COVID19 outpatient US veterans with cancer vary according to race (white vs non-Hispanic black). Less is known about ethnic (Hispanic vs non-Hispanic) disparities in hospitalization rates. We aimed to identify ethnic disparities in all-cause hospitalization rates among COVID19 outpatient US veterans with cancer. Methods: We conducted a retrospective cohort study of veterans with cancer and an index diagnosis of COVID19 (ICD10 U07) between 1/1/2020 and 3/31/2022 managed at the South Texas Veterans Health Care System. We included patients for whom ethnicity data (Hispanic or non-Hispanic white) were available. Our primary outcome was all-cause hospitalization rates at 30 days and 60 days following an index diagnosis of COVID19 among Hispanic and non-Hispanic white patients with cancer. We analyzed continuous variables using unpaired t test and categorical variables using Chi-square analysis for statistical significance (p &lt; 0.05). Results: Of 968 outpatient veterans with a history of cancer and a COVID19 diagnosis between 1/1/2020 and 3/31/2022, 762 met our inclusion criteria. Of these, 300 (39.4%) identified as Hispanic (94% male, p &lt; 0.05) and 462 (60.6%) identified as non-Hispanic white (90% male). At baseline Hispanic patients were younger and were more likely to have underlying comorbidities (T2DM, mild liver disease, AIDS; p &lt; 0.05). Hispanic patients with cancer demonstrated hospitalization rates after the index COVID19 diagnosis comparable to those of non-Hispanic white patients at 30d (34% vs 28.8%) and 60d (35.7% vs 32%). Conclusions: Although Hispanic patients with cancer demonstrated a trend of higher hospitalization rates at 30d and 60d following a COVID19 diagnosis, this difference was not statistically significant. Further studies with a larger sample size and generalizability to assess ethnic disparities in other clinical settings are warranted.

THU-208 - Hepatitis C virus (HCV) infection and neurocognitive impairment in subjects with mild liver disease

THU-208 - Hepatitis C virus (HCV) infection and neurocognitive impairment in subjects with mild liver disease

THU-184 - Hepatitis C virus (HCV) infection and neurocognitive impairment in subjects with mild liver disease: the role of neuropsychological and cognitive provoked P300 tests

THU-184 - Hepatitis C virus (HCV) infection and neurocognitive impairment in subjects with mild liver disease: the role of neuropsychological and cognitive provoked P300 tests

Real-world utilization pattern of pexidartinib in patients with tenosynovial giant cell tumor (TGCT).

e18792 Background: In August 2019, pexidartinib became the first and only systemic therapy approved in the US for the treatment of symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. As TGCT is a rare condition, real-world pexidartinib utilization data are limited and greatly needed to inform clinical use. Methods: Adults (≥18 years) with ≥1 pexidartinib claim from 8/2/2019 - 1/1/2022 identified in the IQVIA Longitudinal Prescription Claims (LRx) linked with Medical Claims (Dx) databases were analyzed. Patient characteristics 6 months before first (index) pexidartinib claim were summarized. Pexidartinib dosing, interruption, and treatment duration were assessed post-index. Discontinuation was defined as treatment gap of ≥90 days. Results: Of 167 patients treated with pexidartinib (median age, 45 years; 59.9% female), the most common comorbidities were osteoarthritis (10.8%), hypertension (8.4%), and obesity (7.8%); 3 patients (1.8%) had mild liver disease and none had moderate-to-severe liver disease pre-index. Median starting dose was 800 mg/day (Table). Over median follow-up of 17.9 months, median (IQR) dose was 622 (442-750) mg/day. Dose reduction was observed in 57 (34.1%) patients and dose increase in 14 (8.4%) patients. Probability of discontinuation was 24.0%, 38.3% and 53.7% at 3-, 6- and 12-month follow-up, respectively. Median (95% confidence interval [CI]) time to pexidartinib discontinuation was 10.1 (7.1, 13.0) months. Fourteen (8.4%) patients restarted pexidartinib after discontinuation. Overall, median (95% CI) time on treatment was 14.2 (10.1, 18.4) months when treatment duration after restart of therapy was considered. Rate of joint surgery after pexidartinib treatment was low (7.2%, n = 12) with median (IQR) time from index to surgery of 5.4 (4.2-12.5) months and median time from last pexidartinib claim to surgery of 2.7 (1.0-8.2) months. Three patients restarted pexidartinib after surgery. Conclusions: Compared to patients in ENLIVEN, real-world pexidartinib patients had similar demographic characteristics. Real-world average daily dose was lower than the full dose recommended in the prescribing information. Compared to ENLIVEN, rate of discontinuation was higher in first 6 months but similar at 12 months. Findings could inform treatment strategy in clinical practice and future research in TGCT. [Table: see text]

WED-315 - Celiac disease in patients with autoimmune hepatitis is associated with a milder liver disease course and a better chance of immunosuppressive treatment withdrawal

WED-315 - Celiac disease in patients with autoimmune hepatitis is associated with a milder liver disease course and a better chance of immunosuppressive treatment withdrawal

P288 The effects of stopping ursodeoxycholic acid in adult patients with mild cystic fibrosis-related liver disease (CFLD)

Ursodeoxycholic acid (UDCA) has been used to treat people with CFLD for years, and usually started in childhood or adolescence. This study aims to assess the effect of stopping UDCA on Liver Function Tests (LFT’s) and liver stiffness measurement (LSM) using ultrasound shear wave elastography of adult patients with CF-related liver disease (PwCFLD) under the care of the All Wales Adult CF Centre (AWACFC).

Rise in alanine aminotransferase after HCV treatment is a highly sensitive screen for treatment failure.

Nucleic acid testing to confirm sustained virological response (SVR) after HCV therapy is technical, often expensive, and frequently unavailable where disease prevalence is highest. Alternative surrogate biomarkers merit evaluation. In a short-treatment trial in Vietnam (SEARCH-1; n = 52) we analysed how changes in alanine transaminase (ΔALT) and aspartate transaminase (ΔAST), from end of treatment (EOT) to EOT + 12 weeks, related to SVR, defined as HCV RNA < lower limit of quantification 12 weeks after EOT. In a separate UK trial (STOPHCV1; n = 202), we then tested the hypothesis that any elevation in ALT or AST between EOT and EOT12 is a sensitive screen for treatment failure. In SEARCH-1, among 48 individuals with data, 13 failed to achieve SVR. Median ΔALT and ΔAST were negative in cured patients but elevated when treatment failed [median ΔALT (IQR): -2 IU/L (-6, +2)] versus +17 IU/L (+7.5, +38) (p< 0.001). Amongst treatment failures, 12/13 had increase in ALT and 13/13 had increase in AST after EOT, compared with 12/35 in those cured. In STOPHCV1, 196/202 patients had evaluable data, of which 57 did not achieve SVR. A rise in ALT after EOT was 100% sensitive (95% C.I. [93.7 - 100%]) and 51% specific (42.4 - 59.7%) for detecting treatment failure. ΔAST >0 IU/L was 98.1% (89.9 - 99.9%) sensitive and 35.8% (27.3 - 45.1%) specific. A rise in ALT or AST after HCV therapy is a highly sensitive screen for treatment failure in mild liver disease. This finding could reduce costs and complexity of managing HCV.

Abstract P1-07-04: Claims-derived comorbidities associations with real-world overall survival (rwOS) among patients with metastatic breast cancer in an electronic health record-claims linked dataset

Abstract Introduction: Comorbid conditions can significantly impact various aspects of cancer care and therefore are often utilized as covariates to control for selection bias in observational studies. Oncology based electronic health record (EHR) data is often used as a source for comorbidity information but may be subject to missingness due to differences in clinician documentation. Utilizing additional data sources, such as health care claims data, may allow for greater capture of comorbidities. This study used a claims data linked to oncology EHR to identify comorbidities and related patient characteristics, as well as the association between a claims-derived comorbidity index and real-world overall survival (rwOS) among outpatient metastatic breast cancer (mBC) patients, to characterize the comorbidities data from this data source. Methods: We selected patients diagnosed with mBC between 2013 and 2021 from a linkage of mBC de-identified EHR-derived Flatiron Health Research Database (FHRD) and Komodo Health claims data. Charlson Comorbidity Index (CCI) were identified based on the presence of a pre-specified International Classification of Diseases (ICD) codes within 12 months preceding cancer diagnosis. To understand comorbidity data within this linkage, patient characteristics were assessed after the study cohort was stratified by the presence of any comorbidity assessed as part of CCI. We calculated the CCI for the study cohort as well as the prevalence of comorbid conditions that are used as part of the CCI. Kaplan-Meier estimates and Cox proportional hazards model were used to estimate median survival time and hazard ratios (HRs) of rwOS among patients with a CCI score of 1 and 2+. Results: The study cohort had 3,213 patients with a median age of 63 [IQR(52, 76)] and 98.7% were female. White patients accounted for 60.1% of the study population while Black and Hispanic/Latino patients accounted for 12.5% and 7.4% of the study cohort, respectively. Patients with comorbidities were older (mean age of 65 vs 61), had a higher (2+) ECOG performance status (PS) score (14.0% vs 9.7%), and were more likely to be Black (16.0% vs 11.0%) or Hispanic/Latino 10.8% vs 6.3%). Twenty percent of the patients had diabetes, 8.2% had peripheral vascular disease, 7.5% had mild liver disease, and 6.3% had congestive heart failure. According to index values, 21.0% of the study cohort had a CCI score of 1, and 18.0% had a score of 2 and above. The median survival times in years for patients with a CCI score of 1 and 2+ were 2.51 [95% CI 2.29,2.81] and 2.05 [95% CI 1.83,2.42], respectively. Based on univariate analysis, patients with a CCI score greater than zero had a higher risk of mortality (CCI 1: HR = 1.25 [95%CI 1.10, 1.41, p&amp;lt; 0.01], CCI 2+: HR = 1.54 [95%CI 1.35, 1.76, p&amp;lt; 0.01]). In the multivariate analysis, adjusted for age, ethnicity/race, and baseline ECOG PS score, the HR for the CCI 1 group was not statistically significant (HR=1.12 [95%CI 0.99, 1.27, p=0.08]). However, the risk of mortality was statistically significant for the CCI 2+ group (HR=1.31 [95%CI 1.14, 1.50], p &amp;lt; 0.01) in the adjusted analysis. Conclusion: Claims data linked to EHR can be used to identify comorbidities and describe patient characteristics. As anticipated, generally, the presence of more comorbid conditions was associated with worse rwOS for patients with mBC. This finding supports use of this linked dataset for similar future studies. Citation Format: Mustafa S. Ascha, Alemseged A. Asfaw, Prakirthi Yerram, Samantha N. Reiss, Sarah D. Brake, Niquelle B. Wadé. Claims-derived comorbidities associations with real-world overall survival (rwOS) among patients with metastatic breast cancer in an electronic health record-claims linked dataset [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-07-04.

People with autoimmune hepatitis and celiac disease have a milder liver disease course and a better chance of immunosuppressive treatment withdrawal.

People with autoimmune hepatitis and celiac disease have a milder liver disease course and a better chance of immunosuppressive treatment withdrawal.

The Charlson comorbidity index and short-term readmission in patients with heart failure: A retrospective cohort study.

The relationship between the Charlson comorbidity index (CCI) and short-term readmission is as yet unknown. Therefore, we aimed to investigate whether the CCI was independently related to short-term readmission in patients with heart failure (HF) after adjusting for other covariates. From December 2016 to June 2019, 2008 patients who underwent HF were enrolled in the study to determine the relationship between CCI and short-term readmission. Patients with HF were divided into 2 categories based on the predefined CCI (low < 3 and high > =3). The relationships between CCI and short-term readmission were analyzed in multivariable logistic regression models and a 2-piece linear regression model. In the high CCI group, the risk of short-term readmission was higher than that in the low CCI group. A curvilinear association was found between CCI and short-term readmission, with a saturation effect predicted at 2.97. In patients with HF who had CCI scores above 2.97, the risk of short-term readmission increased significantly (OR, 2.66; 95% confidence interval, 1.566-4.537). A high CCI was associated with increased short-term readmission in patients with HF, indicating that the CCI could be useful in estimating the readmission rate and has significant predictive value for clinical outcomes in patients with HF.

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study.

World Health Organization has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of direct-acting antiviral (DAA) therapy for hepatitis C. We evaluated early virological response as a means of shortening treatment and explored host, viral and pharmacokinetic contributors to treatment outcome. Duration of sofosbuvir and daclatasvir (SOF/DCV) was determined according to day 2 (D2) virologic response for HCV genotype (gt) 1- or 6-infected adults in Vietnam with mild liver disease. Participants received 4- or 8-week treatment according to whether D2 HCV RNA was above or below 500 IU/ml (standard duration is 12 weeks). Primary endpoint was sustained virological response (SVR12). Those failing therapy were retreated with 12 weeks SOF/DCV. Host IFNL4 genotype and viral sequencing was performed at baseline, with repeat viral sequencing if virological rebound was observed. Levels of SOF, its inactive metabolite GS-331007 and DCV were measured on days 0 and 28. Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and 1 withdrew. SVR12 was achieved in 21/34 (62%) treated for 4 weeks, and 17/17 (100%) treated for 8 weeks. Overall, 38/51 (75%) were cured with first-line treatment (mean duration 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance-associated substitutions (RASs), all first-line treatment failures cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS, SOF or DCV levels. Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use in patients with mild liver disease, while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4-week treatment. Funded by the Medical Research Council (Grant MR/P025064/1) and The Global Challenges Research 70 Fund (Wellcome Trust Grant 206/296/Z/17/Z).