Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients with Primary Biliary Cholangitis

Patients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort. TARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal-Wallis tests were used to compare differences in symptoms between groups. A total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%). The prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus

Prevalence and Factors Associated With Statin Use Among Patients With Nonalcoholic Fatty Liver Disease in the TARGET-NASH Study

Patients with nonalcoholic fatty liver disease (NAFLD) are at an increased risk of cardiovascular disease. Hydoxy-3-methyglutaryl-coenzyme reductase inhibitors, statins, reduce the risk of cardiovascular events.1 Studies have shown that statins are safe among patients with liver disease, including those with compensated cirrhosis,2 and their use is associated with lower mortality, hepatic decompensation, and possibly hepatocellular carcinoma.3,4 Despite these data, statins are under prescribed among patients with liver disease due to concerns about hepatotoxicity.5 This study aimed to assess prevalence and patient factors associated with indicated statin use in patients with NAFLD in a real-world cohort

Validation of a Clinical Risk-based Classification System in a Large Nonalcoholic Fatty Liver Disease Real-world Cohort

There is an unmet need to validate simple and easily available methods that can be used in routine practice to identify those at risk of adverse outcomes from nonalcoholic fatty liver disease (NAFLD). A retrospective-prospective analysis of NAFLD patients enrolled in a longitudinal noninterventional study (TARGET-NASH) was performed to validate the prognostic utility of the following risk-categories: (A) Fibrosis-4 (FIB-4) 2.6 and/or LSM >12.5 kp. Those in class A with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm , or class B with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm were upstaged by one class. Fine-Gray competing risk analyses were performed for all outcomes. A total of 2523 individuals (class A = 555, B = 879, C = 1089) were followed for a median duration of 3.74 years. Adverse outcomes increased from class A to C in all-cause mortality (0.07 vs 0.3 vs 2.5/100 person-years [PY], hazard ratio [HR], 3.0 and 16.3 class B and C vs A), liver-associated clinical events (0.2 vs 1 vs 8/100 PY, HR, 4.3 and 36.6 B and C vs A), major adverse cardiovascular events (0.69 vs 0.87 vs 2.02/100 PY, HR, 0.78 and 1.55 B and C vs A), hepatocellular carcinoma (0 vs 0.09 vs 0.88/100 PY, HR, 8.32 C vs B), and chronic kidney disease (1.24 vs 2.48 vs 3.51/100 PY). Those who were upstaged had outcome rates similar to the lower class defined by their FIB-4. These data support a FIB-4-based risk-stratification of NAFLD that can be used in routine clinical practice. gov Identifier: NCT02815891

Impact of itch on quality of life in people with primary biliary cholangitis: A plain language summary

What is this summary about? This is a summary of an article about people with primary biliary cholangitis (PBC) who also suffer from itch. PBC is a disease that affects the liver; itching is common in PBC and can dramatically reduce a person's quality of life. People in a study called TARGET-PBC filled in surveys about their PBC symptoms, including itching, and the effects the symptoms had on their lives. Information was also collected on the medications people were taking for their PBC and itch. What were the results? Out of 211 people with PBC who filled in the surveys, 170 (81%) had itching. More than one-third of them (37%) had itch that was clinically significant. Clinically significant itch has been defined as an itch that sometimes affects a person's sleep, makes them scratch until their skin is raw, or causes embarrassment. These people would benefit from a discussion about treatment options. Clinically significant itch was linked with worse scores on the surveys, meaning poorer quality of life. This link was true for all areas looked at, but particularly for social aspects and cognition, such as memory and concentration. Sleep was affected in most people with clinically significant itch and there were high levels of fatigue. People with clinically significant itch were more likely to be taking anti-itch medication compared with those with mild itch, but onethird of them still had not received any treatment for itch. When itch medication was used, the stepwise guidelines suggested by specialty professional societies was not usually followed. What do the results mean? Itching is problematic for the people in this study. Those with clinically significant itch have a worse quality of life compared with those with mild itch and this affects all areas of their life measured. The study also shows that people do not always receive medication for their itch, and that treatment guidelines are not always followed

A Real‐World Observational Cohort of Patients with Hepatocellular Carcinoma: Design and Rationale for TARGET‐HCC

This study describes the design of the TARGET‐hepatocellular carcinoma (HCC) cohort and descriptive characteristics of the patient population at diagnosis among those who were enrolled in the cohort across academic and community clinical centers. TARGET‐HCC is a 5‐year, longitudinal, observational cohort of patients with HCC receiving care in usual clinical practice. Redacted clinical information, obtained from medical records, captures the natural history and management of the disease, including the safety and efficacy of treatment interventions used in usual clinical practice. Patients can complete patient‐reported outcome measures and provide biological specimens for future translational studies. The TARGET‐HCC study includes adults with histologic, cytologic, or radiologic diagnosis of HCC from academic and community centers in both the United States and Europe. A total of 1,841 participants were enrolled between January 9, 2017, and July 23, 2019, at 67 sites in the United States and Europe. To date, the most common liver disease etiology in the cohort continues to be hepatitis C, although nearly half had a nonviral etiology, including alcohol‐related liver disease or nonalcoholic steatohepatitis. Most included patients were diagnosed at an early stage (Barcelona Clinic Liver Cancer Stage [BCLC] 0/A), but only approximately one third underwent curative treatment. Systemic therapy has been used in 7.3% of enrolled patients, including 45.7% of those with BCLC stage C tumors. Conclusion: Overall, the TARGET‐HCC cohort allows for the assessment of patient characteristics and investigation of new treatment paradigms and sequencing with existing agents as well as novel regimens for HCC

Variation in Alanine Aminotransferase in Children with Non-Alcoholic Fatty Liver Disease

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a major public health concern. Aminotransferase (ALT) is frequently used for screening and monitoring, but few studies have reported typical patterns of ALT elevation in children. Methods: TARGET-NASH is a real-world longitudinal observational cohort of patients with NAFLD receiving care across the United States. Analyses included children enrolled between 1 August 2016, and 12 October 2020, with at least one ALT measurement after enrollment. Peak ALT was based on the first and last available record and categorized into clinical cut points: 70–250 IU/L. A chi-squared test was used to compare differences in proportions, and a Kruskal–Wallis test was used to compare the medians and distributions of continuous responses. Results: Analyses included 660 children with a median age of 13 years. Of the 660, a total of 187 had undergone a biopsy and were more likely to be Hispanic or Latino (67% vs. 57%, p = 0.02) and to have cirrhosis (10% vs. 1%, p 70 U/L. Conclusions: Large variability was seen in ALT among children, including many values > 250 U/L. Higher levels of ALT were associated with increased prevalence of comorbidities and more advanced stages of NAFLD. These findings support an increased need for therapeutics and disease severity assessment in children with peak ALT > 70 U/L

Patient Determinants for Histologic Diagnosis of NAFLD

Much of the current data on nonalcoholic fatty liver disease (NAFLD) are derived from biopsy‐based studies that may introduce ascertainment and selection bias. Selection of patients for liver biopsy has implications for clinical practice and the reported epidemiology of NAFLD. The aim of this study was to determine patient factors predictive of histologic versus empiric clinical diagnosis of NAFLD in real‐world practice. Adults from TARGET‐NASH were included in this study. Descriptive statistics are provided for the cohort and compare the characteristics of histologic NAFLD versus patients with clinically diagnosed NAFLD, followed by logistic regression and machine‐learning models to describe predictors of liver biopsy. The records of 3,474 subjects were analyzed; median age was 59 years, 59% were female, 75% were White, and median body mass index was 32 kg/m(2). Using histologic and/or clinical criteria, a diagnosis of nonalcoholic steatohepatitis was made in 37%, and cirrhosis in 33%. Comorbid conditions included cardiovascular disease (19%), mental health diagnoses (49%), and osteoarthritis (10%). Predictors of a biopsy diagnosis included White race, female sex, diabetes, and elevated alanine aminotransferase (ALT). ALT increased the odds of liver biopsy by 14% per 10‐point rise. Machine‐learning analyses showed non‐White patients with ALT <69 had only a 0.06 probability of undergoing liver biopsy. ALT was the dominant variable that determined liver biopsy. Conclusions: In this real‐world cohort of patients with NAFLD, two‐thirds of patients did not have a liver biopsy. These patients were more likely to be non‐White, older, with a normal ALT, showing potential gaps in or knowledge about this population