Background & Aims Characterization of relative adrenal insufficiency (RAI) in cirrhosis is heterogeneous with regard to studied patient populations and diagnostic methodology. We aimed to describe the prevalence and prognostic importance of RAI in non‐critically ill patients with cirrhosis. Methods A systematic review and meta‐analysis was performed using MeSH terms and Boolean operators to search five large databases (Ovid‐MEDLINE, ScienceDirect, Web of Science, Cochrane Library and http://clinicaltrials.gov). The population of interest was patients with cirrhosis and without critical illness. The primary outcome was the pooled prevalence of RAI as defined by a peak total cortisol level <18 μg/dl, delta total cortisol <9 μg/dl or composite of the two thresholds in response either a standard‐dose or low‐dose short synacthen test. Odds ratios and standardized mean differences from random‐effects models estimated important clinical outcomes and patient characteristics by adrenal functional status. Results Twenty‐two studies were included in final analysis, comprising 1991 patients with cirrhosis. The pooled prevalence of RAI was 37% (95% CI 33–42%). The prevalence of RAI varied by Child–Pugh classification, type of stimulation test used, specific diagnostic threshold and by severity of illness. Ninety‐day mortality was significantly higher in patients with RAI (OR 2.88, 95% CI 1.69–4.92, I2 = 15%, p < 0.001). Conclusions Relative adrenal insufficiency is highly prevalent in non‐critically ill patients with cirrhosis and associated with increased mortality. Despite the proposed multifactorial pathogenesis, no studies to date have investigated therapeutic interventions in this specific population.
To the Editor, We thank Dr. Lee and colleagues for their interest in our systematic review and meta-analysis on relative adrenal insufficiency (RAI) in cirrhosis 1 and wish to comment on their letter. 2 We agree that total cortisol (TC) levels are an imperfect assessment of patient adrenal function in cirrhosis given their dependence on the availability of liver-derived binding proteins. This is high-
Background Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the two most common primary liver tumors. Proton Beam Therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation, limiting damage to nearby structures. We present a single center experience on liver toxicity, tumor response, and survival in patients with HCC and iCCA treated with PBT with Pencil Beam Scanning (PBS).MethodsConsecutive patients receiving PBT for HCC or iCCA were reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy using PBS. Tumor size was approximated by clinical target volume (CTV). Liver toxicity was determined by changes in MELD-Na and albumin-bilirubin (ALBI) grade. Tumor response was determined by imaging at six to eight weeks post-therapy.Results44 consecutive patients were included, 22 patients in each group. 35% of patients had multifocal disease and median CTV was 232.5cc. Overall survival was 82%. For both cancer types, tumor size, laboratory values, and total radiation dose were not associated with liver toxicity. All iCCA patients had stable or improved ALBI grade following treatment, however there were 4 deaths. Among HCC patients, ALBI grade was stable in 83%, average MELD-Na score remained stable, and there was only one death.ConclusionsOur results indicate that PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis who received biologically effective doses ≥80.5 Gy. Overall survival was 86.4%, similar between HCC and iCCA.
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