Long-term continuous terlipressin infusion improves cardiac reserve in patients with decompensated cirrhosis.

BACKGROUND AND AIMS: Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis. METHODS: Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve; the change in cardiac output (CO) in response to stress. RESULTS: Median age was 61 years (IQR 56-64), median MELD score was 15 (IQR 12.3-17.0) and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0L/min [↑57.8%]) as compared to baseline (↑1.8L/min [21.3%], p=0.0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (p=0.02), driven primarily by improvement in inotropic function. Resting cardiac output (CO) decreased significantly after terlipressin from 8.9±2.2L/min to 7.2±1.8 L/min (p<0.001, normal range 5-6L/min), due to a decrease in stroke volume from 108 to 86mL/beat (p=0.006). CONCLUSION: Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. ANZCTR NUMBER: (http://www.anzctr.org.au/): ACTRN12619000891123.

Computed Tomography-Derived Extracellular Volume Fraction and Splenic Size for Liver Fibrosis Staging.

OBJECTIVE: Extracellular volume fraction (fECV) and liver and spleen size have been correlated with liver fibrosis stages and cirrhosis. The purpose of the current study was to determine the predictive value of fECV alone and in conjunction with measurement of liver and spleen size for severity of liver fibrosis. METHODS: This was a retrospective study of 95 subjects (65 with liver biopsy and 30 controls). Spearman rank correlation coefficient was used to assess correlation between radiological markers and fibrosis stage. Receiver operating characteristic analysis was performed to assess the discriminative ability of radiological markers for significant (F2+) and advanced (F3+) fibrosis and cirrhosis (F4), by reporting the area under the curve (AUC). RESULTS: The cohort had a mean age of 51.4 ± 14.4 years, and 52 were female (55%). There were 36, 5, 6, 9, and 39 in fibrosis stages F0, F1, F2, F3, and F4, respectively. Spleen volume alone showed the highest correlation (r = 0.552, P < 0.001) and AUCs of 0.823, 0.807, and 0.785 for identification of significant and advanced fibrosis and cirrhosis, respectively. Adding fECV to spleen length improved AUCs (0.764, 0.745, and 0.717 to 0.812, 0.781, and 0.738, respectively) compared with splenic length alone. However, adding fECV to spleen volume did not improve the AUCs for significant or advanced fibrosis or cirrhosis. CONCLUSIONS: Spleen size (measured in length or volume) showed better correlation with liver fibrosis stages compared with fECV. The combination of fECV and spleen length had higher accuracy compared with fECV alone or spleen length alone.

The impact of hepatic and splenic volumetric assessment in imaging for chronic liver disease: a narrative review.

Chronic liver disease is responsible for significant morbidity and mortality worldwide. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) can fully visualise the liver and adjacent structures in the upper abdomen providing a reproducible assessment of the liver and biliary system and can detect features of portal hypertension. Subjective interpretation of CT and MRI in the assessment of liver parenchyma for early and advanced stages of fibrosis (pre-cirrhosis), as well as severity of portal hypertension, is limited. Quantitative and reproducible measurements of hepatic and splenic volumes have been shown to correlate with fibrosis staging, clinical outcomes, and mortality. In this review, we will explore the role of volumetric measurements in relation to diagnosis, assessment of severity and prediction of outcomes in chronic liver disease patients. We conclude that volumetric analysis of the liver and spleen can provide important information in such patients, has the potential to stratify patients' stage of hepatic fibrosis and disease severity, and can provide critical prognostic information. CRITICAL RELEVANCE STATEMENT: This review highlights the role of volumetric measurements of the liver and spleen using CT and MRI in relation to diagnosis, assessment of severity, and prediction of outcomes in chronic liver disease patients. KEY POINTS: Volumetry of the liver and spleen using CT and MRI correlates with hepatic fibrosis stages and cirrhosis. Volumetric measurements correlate with chronic liver disease outcomes. Fully automated methods for volumetry are required for implementation into routine clinical practice.

Safety and Effectiveness of Janus Kinase Inhibitors in the Management of Inflammatory Bowel Disease Following Liver Transplantation.

BACKGROUND: The management of inflammatory bowel disease [IBD] patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase [JAK] inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia. METHODS: All liver transplant recipients from the Australian states of Victoria, New South Wales, and Tasmania, who required tofacitinib or upadacitinib for the treatment of IBD, were identified using prospectively maintained liver transplant databases. Patients were followed up until medication cessation or last follow-up. Clinical safety and efficacy data were collected. RESULTS: Eight patients [median age 30 years] were included, seven of whom received first-line JAK inhibition with tofacitinib. All patients had failed one or more biologic therapies prior to commencing JAK inhibition, including six patients who had failed two or more agents. JAK inhibition was continued for a median of 17 months, with 143 patient-months of combined follow-up. The anti-rejection medication tacrolimus was prescribed in all patients. Overall, seven [88%] patients achieved clinical remission, including all three patients who were switched from tofacitinib to upadacitinib. One patient required colectomy after 1 month of treatment. There were no other cases of serious infection, venous thromboembolism, or major adverse cardiovascular events during follow-up. CONCLUSIONS: As the largest case series to date, these data indicate that combining JAK inhibition with transplant anti-rejection medication may be a safe and clinically effective method of treating IBD in patients with prior biologic failure.

Continuous home terlipressin infusion increases handgrip strength and reduces ascites-A prospective randomized crossover study.

BACKGROUND AND AIMS: Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension. APPROACH AND RESULTS: This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema. CONCLUSIONS: This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.

Reversing malnutrition and low muscle strength with targeted enteral feeding in patients awaiting liver transplant: A randomized controlled trial.

BACKGROUND AND AIMS: Most patients with decompensated cirrhosis fail to meet their nutrition targets. The impact of nasogastric feeding (NGF) on malnutrition in cirrhosis remains unknown. This study aims to assess the impact of pretransplant NGF on pre-liver transplant and post-liver transplant outcomes. APPROACH AND RESULTS: This single-center, prospective randomized controlled trial of 55 patients with severe malnutrition and low handgrip strength (HGS) compared a standard high-energy high-protein diet to diet plus supplemental nocturnal NGF while awaiting transplant. The primary outcome was a change in HGS. The median age was 58.5 years (IQR: 51.1-64), median MELD was 24 (20-28.5), and 32 (58%) patients were male. The median duration of NGF was 63.0 days (34.5-127), following which time the median between-group difference in HGS was 3.6 kg (95% CI: 1.7-5.2, p <0.001), an increase of 20% from baseline. Mid-upper-arm circumference, triceps skinfold, and immune function all increased significantly with NGF. Muscle and nutritional parameters continued to improve with increasing duration of feeding. NGF significantly increased daily energy intake between groups by 1285 kcal (95% CI: 860-1677) and protein intake by 51 g (95% CI: 32-71) (both p <0.001). All NGF patients met >100% of their measured nutritional requirements. Posttransplant clinical outcomes were similar between groups. CONCLUSIONS: Targeted enteral feeding before liver transplant improves HGS, anthropometry, and immune function in severely malnourished patients with cirrhosis. These findings provide a strong rationale for early consideration of NGF to reverse malnutrition and improve muscle strength. Appropriately powered studies should explore whether NGF can also impact clinically relevant outcomes including pretransplant and posttransplant mortality.

Branched-chain amino acid supplementation does not improve measures of sarcopenia in cirrhosis: results of a randomised controlled trial.

BACKGROUND: Sarcopenia is associated with adverse outcomes in cirrhosis. Branched-chain amino acids (BCAA) target several pathways that lead to muscle loss in this population. AIMS: We aimed to evaluate the impact of BCAA supplementation on sarcopenia measures in patients with cirrhosis. METHODS: We conducted a 12-month double-blinded, randomised, controlled trial of BCAA supplementation (30 g daily) compared to an equicaloric, equi-nitrogenous whey protein in volunteers with cirrhosis and reduced muscle strength. The primary endpoint was an increase in grip strength and upper limb lean mass measured on DEXA. Mean-adjusted differences (MAD, 95% CI) between groups at 6 and 12 months are reported as treatment effect using a linear mixed model for repeated measures. RESULTS: A total of 150 volunteers entered the trial (74 BCAA, 76 control), with a median age of 58 years [IQR 48; 63] and MELD of 14 [12; 17]. At 12 months, 57% in the BCAA arm and 61% in the control arm met the primary endpoint (p = 0.80). No significant between-group difference was found in grip strength (MAD -0.15 kg [-0.37; 0.06], p = 0.29) or upper limb lean mass (1.7 kg [-0.2; 3.6], p = 0.22) at 12 months. No significant differences in other body composition parameters, physical performance, frailty, rates of hospitalisation or mortality were found between the BCAA and the control group. Fatigue improved across the entire cohort, without significant between-group differences. 15% of volunteers reported side effects, with distaste higher in the BCAA arm (p = 0.045). CONCLUSION: BCAA supplementation did not improve measures of muscle strength, mass or performance or physical frailty compared to a whey protein supplement in a randomised controlled setting. ACTRN12618000802202.

Enhancing pre-transplant cardiac assessment: Validation and utility of the CAD-LT score with CCTA in liver transplant candidates.

BACKGROUND: Coronary computed tomography angiography (CCTA) is increasingly being used in the preoperative workup for liver transplantation (LT). We sought to assess the utility of integrating CCTA with the novel CAD-LT (Coronary Artery Disease in Liver Transplantation) score and its impact on reducing the need for invasive coronary angiography prior to LT. METHODS: We conducted a retrospective cohort study of consecutive patients (age ≥ 18 years) who underwent CCTA for LT workup between 2011 and 2018 at the Victorian Liver Transplant Unit, Melbourne, Australia. CAD-LT scores, a traditional risk factor-based criteria, were calculated, and patients stratified as low-, intermediate- or high-risk. RESULTS: Overall, 229 patients underwent CCTA. The mean age was 66 ± 5 years (82% male) with a modest-to-high risk factor burden (diabetes, 53%; hypertension, 46%; current or former smoker, 62%). The mean CAD-LT score of our cohort was 12.4 ± 4.0. No patients were classified as low-risk, 49 patients (21.4%) were deemed intermediate-risk and 180 patients (78.6%) were deemed high-risk. A high CAD-LT score (≥ 9) showed high sensitivity (95.3% [95% CI 86-98%]) and modest specificity (27.8% [95% CI 21-35%]) for the detection of obstructive coronary artery disease on CCTA, with a negative predictive value of 94%. Following multidisciplinary discussions, only 41 patients (18%) of patients proceeded to ICA of which 27% received percutaneous coronary intervention. CONCLUSIONS: The use of CCTA in patients deemed intermediate- to high-risk by the CAD-LT score has the potential to reduce the need for invasive coronary angiography in patients undergoing LT workup.

Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation.

Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.

Graft-derived cfDNA Monitoring in Plasma and Bile During Normothermic Machine Perfusion in Liver Transplantation Is Feasible and a Potential Tool for Assessing Graft Viability.

BACKGROUND: Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study. METHODS: Serial plasma and bile samples were collected during NMP for 10 consecutive grafts, at 15 min post-machine reperfusion and then 2-h intervals. Digital polymerase chain reaction was used to quantify gdcfDNA at each time point. RESULTS: Five grafts were suitable for LT, there were no cases of primary nonfunction or death in the recipients. gdcfDNA was quantified in all bile and plasma samples (n > 100). In plasma, gdcfDNA concentrations climbed post-machine reperfusion until 4.25 h (median 2.25 h = 15.98 × 10 6 copies/mL, 4.25 h = 40.21 × 10 6 copies/mL). gdcfDNA levels then diverged significantly when comparing the viable and non-viable graft groups (6.25 h, median viable: 117.15 × 10 6 copies/mL versus non-viable: 16.72 × 10 6 copies/mL, P = 0.01). These opposing trends correlated in each graft and in all cases with the viable/non-viable outcome. There was a trend of gradual decline in bile gdcfDNA from viable grafts post-machine reperfusion; discarded grafts showed more variable patterns of release. CONCLUSIONS: gdcfDNA analysis during NMP is a feasible and potential tool to inform viability assessment during NMP for LT. Bile gdcfDNA monitoring offers the prospect of an objective means to assess the degree of biliary injury associated with organ procurement.

Redefining Nutritional Requirements in End-Stage Liver Disease: Towards a Personalized Approach.

Malnutrition is ubiquitous in cirrhotic patients presenting for liver transplant (LT). Providing an appropriate energy prescription is fundamental to effective nutrition therapy. We aimed to compare measured energy expenditure (mEE) with predicted energy expenditure (pEE) in patients awaiting LT and determine clinical factors associated with mEE. In this prospective observational study, energy expenditure was measured by indirect calorimetry in 110 adult patients referred for LT and predicted by commonly utilized equations (Harris-Benedict, Schofield, and EASL guidelines). Nutritional status, anthropometry, muscle function, biochemical and clinical data were also collected. The median model for end-stage liver disease (MELD) was 19 (IQR 13, 25), and the majority were Child-Pugh B (51%) or C (37%). Malnutrition was evident in 85%. Median mEE by calorimetry was 1756 (1531, 2104) kcal/d and significantly higher than pEE as per Harris-Benedict 1480 (1322, 1722) kcal/d and Schofield 1474 (1349, 1723) kcal/d (both p < 0.001), but lower than EASL guidelines (35 kcal/kg) when an activity factor was applied to mEE; 2283 (1990, 2735) kcal/d versus 2590 (2178, 3010) kcal/d (p < 0.001). Hypermetabolism (mEE:pEE > 1.2) was evident in 48% of the cohort. Multivariate analysis found MELD, Child-Pugh class, diuretic use, and severe malnutrition to be independent predictors of hypermetabolism. A new liver-specific predictive model has been developed, showing superior agreement with mEE than common predictive equations. In conclusion, there is a poor correlation between mEE and pEE in patients awaiting LTs, and hypermetabolism is common. Relying on historical predictive equations in this patient population may result in significant under or over-feeding. A tailored energy prescription based on indirect calorimetry or a liver-specific predictive model is recommended for LT candidates.

Outcomes of patients with hepatorenal syndrome undergoing liver transplantation in the era of terlipressin.

BACKGROUND: The efficacy of terlipressin in improving pre-liver transplant renal function in hepatorenal syndrome (HRS) has been well documented, however, its impact on post-transplant renal function remains poorly described. This study aims to describe the impact of HRS and terlipressin on post-liver transplant renal function and survival. METHODS: A single-centre, retrospective, observational study was conducted to identify post-transplant outcomes of patients diagnosed with HRS undergoing liver transplant (HRS cohort) and those undergoing transplant for non-HRS, non-hepatocellular carcinoma cirrhotic indications (comparator cohort) between January 1997 and March 2020. The primary outcome was serum creatinine at 180 days post-liver transplant. Other renal outcomes and overall survival were secondary outcomes. RESULTS: 109 patients with HRS and 502 comparator patients underwent liver transplant. The comparator cohort was younger than the HRS cohort (53 vs. 57 years, P < 0.001). The median creatinine at day 180 post-transplant was higher in the HRS transplant group (119 µmol/L vs. 103 µmol/L, P < 0.001), however, this association lost significance following multivariate analysis. Seven patients (7%) in the HRS cohort received a combined liver-kidney transplant. There was no significant difference in the 12-month post-transplant survival between the two groups (94% vs. 94%, P = 0.5). CONCLUSION: Patients with HRS treated with terlipressin who subsequently undergo liver transplantation have post-transplant renal and survival outcomes comparable to patients transplanted for cirrhosis without HRS. This study supports the practice of liver-only transplant in this cohort and the reservation of renal allografts for those who have primary renal disease.

Transjugular intrahepatic portosystemic shunt insertion improves muscle mass but not muscle function or frailty measures.

INTRODUCTION: Sarcopenia in cirrhosis is associated with poor outcomes. While transjugular intrahepatic portosystemic shunt (TIPS) insertion improves radiological measures of muscle mass, its impact on muscle function, performance and frailty has not been evaluated. METHODS: Patients with cirrhosis referred for TIPS were prospectively recruited and followed for 6 months. L3 CT scans were used to calculate skeletal muscle and adipose tissue parameters. Handgrip strength, Liver Frailty Index and short physical performance battery were serially monitored. Dietary intake, insulin resistance, insulin-like growth factor (IGF)-1, and immune function using QuantiFERON Monitor (QFM) were measured. RESULTS: Twelve patients completed the study with a mean age of 58 ±â€…9 years and model for end-stage liver disease score of 16 ±â€…5. At 6 months post-TIPS, skeletal muscle area increased from 139.33 cm 2  ±â€…22.72 to 154.64 ±â€…27.42 ( P  = 0.012). Significant increases were observed in the subcutaneous fat area ( P  = 0.0076) and intermuscular adipose tissue ( P  = 0.041), but not muscle attenuation or visceral fat. Despite marked changes in muscle mass, no improvements were observed in handgrip strength, frailty, or physical performance. At 6 months post-TIPS, IGF-1 ( P  = 0.0076) and QFM ( P  = 0.006) increased compared to baseline. Nutritional intake, hepatic encephalopathy measures, insulin resistance and liver biochemistry were not significantly impacted. CONCLUSION: Muscle mass increased following TIPS insertion as did IGF-1, a known driver of muscle anabolism. The lack of improvement in muscle function was unexpected and may relate to impairment in muscle quality and the effects of hyperammonaemia on muscle contractile function. Improvements in QFM, a marker of immune function, may suggest a reduction in infection susceptibility in this at-risk population and requires further evaluation.

Graft-Derived Cell-Free DNA Quantification following Liver Transplantation Using Tissue-Specific DNA Methylation and Donor-Specific Genotyping Techniques: An Orthogonal Comparison Study.

Background: Graft-derived cell-free DNA (gdcfDNA) analysis has shown promise as a non-invasive tool for monitoring organ health following solid organ transplantation. A number of gdcfDNA analysis techniques have been described; however, the majority rely on sequencing or prior genotyping to detect donor-recipient mis-matched genetic polymorphisms. Differentially methylated regions of DNA can be used to identify the tissue-of-origin of cell-free DNA (cfDNA) fragments. In this study, we aimed to directly compare the performance of gdcfDNA monitoring using graft-specific DNA methylation analysis and donor-recipient genotyping techniques in a pilot cohort of clinical samples from patients post-liver transplantation. Results: 7 patients were recruited prior to LT, 3 developed early, biopsy-proven TCMR in the first 6 weeks post-LT. gdcfDNA was successfully quantified in all samples using both approaches. There was a high level of technical correlation between results using the two techniques (Spearman testing, rs = 0.87, p < 0.0001). gdcfDNA levels quantified using the genotyping approach were significantly greater across all timepoints in comparison to the tissue-specific DNA methylation-based approach: e.g., day 1 post-LT median 31,350 copies/mL (IQR 6731-64,058) vs. 4133 copies/mL (IQR 1100-8422), respectively. Qualitative trends in gdcfDNA levels for each patient were concordant between the two assays. Acute TCMR was preceded by significant elevations in gdcfDNA as quantified by both techniques. Elevations in gdcfDNA, using both techniques, were suggestive of TCMR in this pilot study with a 6- and 3-day lead-time prior to histological diagnosis in patients 1 and 2. Conclusions: Both the graft-specific methylation and genotyping techniques successfully quantified gdcfDNA in patients post-LT with statistically significant concordance. A direct comparison of these two techniques is not only important from a technical perspective for orthogonal validation, but significantly adds weight to the evidence that gdcfDNA monitoring reflects the underlying biology. Both techniques identified LT recipients who developed acute TCMR, with several days lead-time in comparison to conventional diagnostic workflows. Whilst the two assays performed comparably, gdcfDNA monitoring based on graft-specific DNA methylation patterns in cfDNA offers major practical advantages over the donor-recipient genotyping, and hence enhances the potential to translate this emerging technology into clinical practice.

Evaluating treatment response following locoregional therapy for hepatocellular carcinoma: A review of the available serological and radiological tools for assessment.

Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer-related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non-curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post-treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

A Single Centre Experience with Pre-Operative Markers in the Prediction of Outcomes after Liver Resection for Hepatocellular Carcinoma.

BACKGROUND AND AIM: The C-reactive protein to albumin ratio, albumin-bilirubin index and platelet-albumin-bilirubin index have emerged as prognostic scores in hepatocellular carcinoma, although their clinical utility remains unclear, with ongoing investigation in multiple patient populations. This study aims to report survival outcomes and evaluate these indices in a cohort of patients undergoing liver resection for hepatocellular carcinoma in a tertiary Australian centre. METHODS: This retrospective study reviewed data from the Department of Surgery at Austin Health and electronic health records (Cerner corporation). The impact of pre, intra and post-operative parameters on post-operative complications, overall and recurrence free survival were analyzed. RESULTS: 163 liver resections were performed in 157 patients between 2007 and 2020. Post-operative complications occurred in 58 patients (35.6%), with pre-operative albumin < 36.5 g/L (3.41(1.41-8.29),p = 0.007) and open liver resection (3.93(1.38-11.21),p = 0.011) demonstrating independent predictive significance. 1,3 and 5-year overall survival was 91.0%, 76.7% and 66.9% respectively, with a median survival time of 92.7 months (81.3-103.9). Hepatocellular carcinoma recurred in 95 patients (58.3%) with a median time to recurrence of 27.8 months (15.6-39.9). 1,3 and 5 year recurrence-free survival rates were 94.0%, 73.7% and 55.1% respectively. Pre-operative C-reactive protein-albumin ratio > 0.034 was significantly associated with reduced overall (4.39(1.19-16.16),p = 0.026) and recurrence-free (2.53(1.21-5.30),p = 0.014) survival. CONCLUSION: C-reactive protein-albumin ratio > 0.034 is a strong predictor of poor prognosis following liver resection for hepatocellular carcinoma. In addition, pre-operative hypoalbuminemia was associated with post-operative complications, and future studies are required to assess the potential benefits of albumin replacement in reducing post-surgical morbidity.

Cyclosporine as an alternative immunosuppressant for steroid-resistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a multiorgan reaction associated with a broad range of commonly used medications. Most cases of DRESS syndrome resolve with cessation of the inciting agent; however, use of systemic immunosuppression, most commonly with oral corticosteroids, is also recommended in cases with visceral organ involvement.We report a case of steroid-resistant relapsing-remitting DRESS syndrome secondary to sulfasalazine. Our patient experienced significant flare of symptoms of DRESS syndrome with multiple attempts to wean prednisolone. Initiation of cyclosporine as an alternative immunosuppressive agent to long-term corticosteroids has resulted in a 6-month remission in both dermatological and hepatic sequelae of DRESS syndrome.

Clinical and financial impacts of abnormal liver biochemistry after liver transplantation.

OBJECTIVE: After liver transplant (LT), many investigations are needed to evaluate abnormal liver function test (LFT), which has poor specificity for graft function and complication. A single center retrospective audit of all adult single organ LT from 1/1/2015 to 31/12/2017 was performed. Demographic, clinical and investigation data from the LT database and electronic medical records and cost data from the hospital's Business Intelligence Unit were analyzed. Patients were classified into uncomplicated or complicated LFT by 2 independent investigators and the number, type, and cost of investigations in the first 30 post-operative days were analyzed. Investigations prior to liver biopsy was sub-analyzed. RESULTS: There was 170 LT with 87 cases of uncomplicated LFT (51.2%) and 83 cases of complicated LFT (48.8%). Most patients with complicated LFT had additional investigations (97.6%), most commonly cholangiogram (55.4%) and liver biopsy (LBx) (50.6%). The additional investigations cost was $1863.3 (95% CI 1289.0-2437.6). Although most LBx (73.8%) showed evidence of rejection, LBx was often not the initial investigation of choice. Current LFT based post-transplant monitoring is inefficient. It remains difficult to determine which patient will benefit from an early invasive procedure like LBx, using LFT alone without further imaging investigations.