ABSTRACT
Liver tests are commonly performed in primary care and may signal the presence of acute or chronic liver disease. Abnormal results are defined by standardized rather than individual laboratory thresholds and must be interpreted in the context of a patient's history and examination. The pattern and severity of liver injury may provide clues about the cause of disease and should guide diagnostic evaluation with serologic testing and liver imaging. A systematic, stepwise approach to the evaluation and management of abnormal liver test results is recommended to optimize high-value care.
Subject(s)
Liver Diseases/diagnosis , Liver Diseases/therapy , Liver Function Tests , Primary Health Care , Biomarkers/analysis , Diagnosis, Differential , Humans , Medical History Taking , Physical Examination , Severity of Illness IndexABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced malignancies but are associated with diarrhea and colitis. The objective of our systematic review and meta-analysis was to determine the incidence and outcomes of ICI-associated diarrhea and colitis. Bibliographic databases were searched through August 13, 2019, for observational studies of ICI therapy reporting the incidence and/or treatment of diarrhea or colitis. The primary outcome was ICI-associated diarrhea and colitis. Meta-analyses were performed with random-effects models. Twenty-five studies (N=12,661) were included. All studies had a high risk of bias in at least 1 domain. The overall incidence of diarrhea/colitis was 12.8% [95% confidence interval (CI), 8.8-18.2, I2=96.5]. The incidence was lower in patients treated with anti-programmed cell death 1/programmed death-ligand 1 (4.1%, 95% CI, 2.6-6.5) than in those treated with anti-cytotoxic T-cell lymphocyte-associated antigen 4 (20.1%, 95% CI, 15.9-25.1). The remission of diarrhea and/or colitis was higher in patients treated with corticosteroids plus biologics (88.4%, 95% CI, 79.4-93.8) than in those treated with corticosteroids alone (58.3%, 95% CI, 49.3-66.7, Q=18.7, P<0.001). ICI were permanently discontinued in 48.1% of patients (95% CI, 17.8-79.1). ICI were restarted after temporary interruption in 48.6% of patients (95% CI, 18.2-79.4) of whom 17.0% (95% CI, 6.4-30.0) experienced recurrence. Real-world incidence of ICI-associated diarrhea/colitis exceeds 10%. These events lead to permanent ICI discontinuation in just over 50% of patients, while <20% have recurrence of symptoms if ICI are resumed. Further studies are needed to identify patients who would benefit from early treatment with biologics as well as appropriate patients to resume ICI therapy.
Subject(s)
Colitis/chemically induced , Diarrhea/chemically induced , Immune Checkpoint Inhibitors/adverse effects , Adrenal Cortex Hormones/therapeutic use , Biological Products/therapeutic use , Colitis/drug therapy , Colitis/epidemiology , Diarrhea/drug therapy , Diarrhea/epidemiology , Humans , Incidence , Neoplasms/drug therapy , Neoplasms/epidemiology , Observational Studies as TopicABSTRACT
Chronic hepatitis C virus infection remains a national and global public health burden and is associated with significant morbidity and mortality. Oral direct-acting antiviral combination regimens have excellent tolerability and efficacy with rates exceeding 90%. Sustained virologic response is associated with significant improvements in clinical outcomes. However, translation of sustained virologic response rates from trials to community settings has been poor with interferon-based regimens. We review and summarize key datasets from major real-world observational cohort studies. We review preliminary data from oral generic direct-acting antiviral formulations. Future real-world studies are needed to further clarify optimal treatment strategies for difficult-to-treat populations.
Subject(s)
Antiviral Agents/therapeutic use , Drugs, Generic/therapeutic use , Hepatitis C, Chronic/drug therapy , Administration, Oral , Antiviral Agents/administration & dosage , Cohort Studies , Drug Therapy, Combination , Drugs, Generic/administration & dosage , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Observational Studies as Topic , Sustained Virologic Response , Treatment OutcomeABSTRACT
BACKGROUND: Treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) regimens has resulted in high rates of sustained virologic response (SVR). Treatment of vulnerable populations may be improved by incorporating an on-site intensive specialty pharmacy (ON-ISP). AIMS: To describe outcomes of HCV treatment at a safety-net hospital and proportion of subjects achieving SVR for those using the ON-ISP compared to an off-site pharmacy (OFF-SP). METHODS: A retrospective cohort study of 219 subjects treated for HCV with DAA at Boston Medical Center was conducted. Subject characteristics, virologic response, and pharmacy services used were recorded. We used multivariable logistic regression to test the association between ON-ISP and SVR after adjusting for covariates. RESULTS: SVR occurred in 71% of subjects by intention-to-treat (73% among ON-ISP users vs 57% among OFF-SP users) and 95% completing treatment per-protocol (96% among ON-ISP users vs 87% among OFF-SP users). Adjustment for age, sex, ethnicity, insurance, fibrosis, prior treatment, and MELD revealed an increased likelihood of SVR among users of ON-ISP: OR 6.0 (95% CI 1.18-31.0). No significant difference in treatment delay or adverse events was seen among users of either pharmacy type. CONCLUSIONS: HCV treatment with DAA was well tolerated, but the rate of SVR was low (71%) compared to trials. This was due to loss to follow-up, as the per-protocol rate of SVR was much higher (95%). Use of ON-ISP was associated with an increase in SVR and may be valuable for improving care for vulnerable populations.
