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Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.

Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.

Background. We examined the association between sarcopenia and post-transplant mortality in acutely ill inpatients with cirrhosis who underwent urgent liver transplantation. Methods. Included were inpatients at 4 centers who were urgently listed as nonstatus 1 and transplanted from 2005 to 2017 with an abdominal computed tomography scan <90 days before transplantation. Skeletal muscle index (SMI) = total skeletal muscle cross-sectional area at the L3 vertebral level, normalized to height. Cox regression associated SMI with post-transplant mortality. Optimal search identified SMI cutoffs to detect survival. Results. Of 126 inpatients, 63% were male patients, model for end-stage liver disease (MELDNa) was 32, and follow up was 5.1 years. Among men, 23% died. Median SMI was lower in men who died versus survived (45 versus 51 cm2/m2). SMI was associated with post-transplant mortality (hazard ratio [HR] = 0.96 per cm2/m2, 95% CI 0.92-0.99). Patients with SMI ≤ 48 cm2/m2 versus >48 cm2/m2 experienced higher rates of death at 1 year (86% versus 95%) and 3 years (73% versus 95%) (Log-rank P = 0.01). In MELD-adjusted analysis, sarcopenia was strongly associated with post-transplant mortality (HR = 4.39, 95% CI 1.49-12.97). Among women, 35% died. Median SMI was similar in women who died versus survived (45 versus 44 cm2/m2). SMI was not associated with post-transplant mortality (HR = 1.02, 95% CI 0.96-1.09). Optimal search did not identify any SMI cutoff that predicted post-transplant mortality. Conclusions. Among patients who underwent urgent inpatient evaluation and liver transplantation, we identified an SMI cutoff value of 48 cm2/m2 to predict post-transplant mortality in men. Our data support the use of SMI as a tool to capture the impact of muscle depletion on post-transplant mortality in acutely ill men with cirrhosis undergoing urgent liver transplantation.

Linked ContentThis article is linked to Ebadi et al and Wang et al papers. To view these articles, visit https://doi.org/10.1111/apt.15029 and https://doi.org/10.1111/apt.15147.

Linked ContentThis article is linked to Ebadi et al and Cheng and Wang papers. To view these articles, visit https://doi.org/10.1111/apt.15029 and https://doi.org/10.1111/apt.15165.

Linked ContentThis article is linked to Ebadi et al and Imga and Efe papers. To view these articles, visit https://doi.org/10.1111/apt.15029 and https://doi.org/10.1111/apt.15075.

SummaryBackgroundVitamin D deficiency has been implicated in the outcome of chronic liver disease.AimTo determine the frequency of severe vitamin D deficiency in autoimmune hepatitis (AIH), assess its association with treatment non‐response, and evaluate the relationship between vitamin D status and liver‐related mortality and need for transplantation.MethodsTwo hundred and nine patients were evaluated by liver tissue examination at presentation. Serum vitamin D levels were determined, and serum levels <25 nmol/L (10 ng/mL) were considered severely deficient. Treatment non‐response was defined as non‐normalised aspartate aminotransferase/alanine aminotransferase and immunoglobulin G levels during conventional immunosuppressive therapy. Univariate and multivariate analyses were performed using binary logistic regression and Cox proportional hazards model.ResultsThe mean vitamin D level was 60 ± 38 nmol/L (range, 3‐263 nmol/L), and 42 patients (20%) had severe vitamin D deficiency. Treatment non‐response was more common in patients with severe vitamin D deficiency than in patients without (59% vs 41%, P = 0.04). Severe vitamin D deficiency was also independently associated with a higher risk of developing cirrhosis (HR 3.40; 95% CI 1.30‐8.87, P = 0.01) and liver‐related mortality or requirement for liver transplantation (LT; HR 5.26, 95% CI, 1.54‐18.0, P = 0.008). Patients with persistent severe deficiency following vitamin D supplementation continued to have poor outcomes.ConclusionsSevere vitamin D deficiency is associated with treatment non‐response, progression to cirrhosis, and liver‐related death or need for LT. Severe vitamin D deficiency is a prognostic biomarker in AIH.

Clinical indications for liver transplantation (LT) in patients with autoimmune hepatitis (AIH) are identical to those of patients with other chronic liver diseases that end in acute or semiacute liver failure, decompensated cirrhosis, or hepatocellular carcinoma. Recurrent disease after LT has been reported in 10%‐50% of patients with AIH, and the frequency of detection is influenced in part by the use of protocol or clinically indicated liver biopsy. De novo AIH connotes the development of AIH in patients transplanted for liver diseases other than AIH, and it has been reported in 5%‐10% of pediatric and 1%‐2% of adult recipients. Recurrent disease can negatively impact on graft and patient survival, and retransplantation has been required in 8%‐23%. De novo AIH is within the spectrum of graft dysfunction that includes plasma cell–rich rejection, and it can also progress to cirrhosis and graft failure. Treatment for recurrent or de novo disease is based on the conventional regimens for AIH, and corticosteroid therapy alone or combined with azathioprine is standard. Better control of disease activity prior to LT has been associated with less recurrence, and maintenance corticosteroid treatment after LT can reduce its frequency. In conclusion, recurrent AIH is far more frequent than de novo AIH. Both may have negative impacts on graft and patient survival, and early detection and treatment are key objectives. Future investigations must codify the diagnostic criteria for each graft dysfunction, seek diagnostic biomarkers, and evaluate treatments that improve outcomes without increasing the risk of pre‐ and post‐LT infections.

AbstractBackgroundSarcopenia, characterized by low muscle mass, associates with mortality in patients with cirrhosis. Skeletal muscle area in a single computed tomography image at the level of the third lumbar vertebrate (L3) is a valid representative of whole body muscle mass. Controversy remains regarding applicability of psoas muscle to identify patients at greater risk of mortality. We aimed to determine psoas muscle index (PMI) association with skeletal muscle index (SMI) and to evaluate the capacity of PMI to predict liver transplant waitlist mortality.MethodsWe evaluated listed adult patients with cirrhosis from 2012 to 2013 at four North American liver transplant centres. From L3 computed tomography images within 3 months of listing, we determined SMI and PMI expressed by cm2/m2. Low SMI was defined as SMI <39 cm2/m2 in women and <50 cm2/m2 in men as published by us earlier. Cut‐offs for PMI to predict mortality were established using a receiver‐operating characteristic analysis. Mortality predictors were determined using competing‐risk analysis with reported results as subdistribution hazard ratios (sHRs).ResultsOf 353 waitlist candidates, 68% were men, mean age 56 ± 9 years, and Model for End‐stage Liver Disease of 16 ± 8 points. Low SMI was present more frequently in men than women (51 vs. 36%, P = 0.02). Moderately strong correlation between SMI and PMI was observed (r > 0.7, P < 0.001). Low PMI (males < 5.1 cm2/m2; females < 4.3 cm2/m2) yielded poor and moderate concordance with low SMI in men and women, respectively (Kappa coefficient 0.31 and 0.63). SMI (39 ± 9 vs. 43 ± 7 cm2/m2; P = 0.009) and PMI (4.4 ± 1.3 vs. 5.2 ± 1.1 cm2/m2; P = 0.001) were lower in women who died and/or were delisted (compared with non‐deceased patients) whereas men who died and/or were delisted had only lower SMI (47 ± 7 vs. 51 ± 9 cm2/m2; P = 0.003), but not PMI compared with non‐deceased patients. In women, both SMI (sHR 0.94, P = 0.048) and PMI (sHR 0.58, P = 0.002) were predictors of mortality, while in men, SMI was significant (sHR 0.95, P = 0.001) and PMI showed a trend to be (sHR 0.85, P = 0.09) associated with mortality. Overall, 104 patients (29%) were misclassified between SMI and PMI categories. Using PMI cut‐offs, 66% and 28% of low SMI men and women, who have a higher risk of mortality, were incorrectly classified as low risk.ConclusionsSkeletal muscle index is a more complete and robust measurement than PMI, especially in men with cirrhosis. Low PMI identifies an incomplete subset of patients at increased risk of mortality indicated by low SMI. Given the poor performance of PMI, SMI should not be substituted by PMI.