Does multimodal perioperative pain management enhance immediate and short-term outcomes after living donor partial hepatectomy? A systematic review of the literature and expert panel recommendations.

BACKGROUND: The optimal analgesic strategy for patients undergoing donor hepatectomy is not known and the potential short- and long-term physical and psychological consequences of complications are significant. OBJECTIVES: To identify whether a multimodal approach to pain of the donor intraoperatively enhances immediate and short-term outcomes after living liver donation, and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO 2021 CRD42021260699. RESULTS: Nine studies assessing multi-modal analgesia strategies were included in a qualitative assessment. Interventions included local, regional, and neuro-axial anesthetic techniques, pharmacological intervention (NSAIDs, COX-2 inhibitors, ketamine, dexmedetomidine, and lidocaine), and acupuncture. Overall, there was a significant (40%) reduction in opioid requirement on day 1 and a significant reduction in pain scores in the intervention vs control groups. Significant reductions in either length of stay or post-operative complications were demonstrated in four of nine studies. CONCLUSIONS: Opioid use for patients undergoing donor hepatectomy is likely to impact both their short- and long-term outcomes. To reduce post-operative pain scores, shorten length of hospital stay, and promote earlier post-operative return of bowel function, we recommend that multi-modal analgesia be offered to patients undergoing living donor hepatectomy. Further research is required to confirm which multi-modal techniques are most associated with enhanced recovery in living liver donors.

Evaluation of coronary artery disease in potential liver transplant recipients.

Improvements in the management of patients undergoing liver transplantation (LT) have resulted in a significant increase in survival in recent years. Cardiac disease is now the leading cause of early mortality, and the stress of major surgery, hemodynamic shifts, and the possibilities of hemorrhage or reperfusion syndrome require the recipient to have good baseline cardiac function. The prevalence of coronary artery disease (CAD) is increasing in LT candidates, especially in those with nonalcoholic fatty liver disease. In assessing LT recipients, we suggest a management paradigm of "quadruple assessment" to include (1) history, examination, and electrocardiogram; (2) transthoracic echocardiogram; (3) functional testing; and (4) where appropriate, direct assessment of CAD. The added value of functional testing, such as cardiopulmonary exercise testing, has been shown to be able to predict posttransplant complications independently of the presence of CV disease. This approach gives the assessment team the greatest chance of detecting and preventing complications related to CAD. Liver Transplantation 23 386-395 2017 AASLD.

Biomarkers of Hepatic Fibrosis in Chronic Hepatitis C: A Comparison of 10 Biomarkers Using 2 Different Assays for Hyaluronic Acid.

BACKGROUND: Advancing fibrosis is regarded as the most important factor when stratifying patients with chronic hepatitis C for retreatment. GOALS: (1) To compare the performance of 10 biomarkers of fibrosis, including patented tests, among patients with chronic hepatitis C and treatment failure; and (2) to assess the impact on biomarker performance of using 2 different assays of hyaluronic acid (HA). STUDY: For 80 patients, liver histology (Metavir) was compared with biomarker scores using sera obtained within 6 months of liver biopsy (indirect biomarkers: AST:ALT ratio, APRI, Forns index, FIB-4, Fibrometer V3G; direct biomarkers: ELF, Fibrospect II, Hyaluronic acid-HA, Fibrometer V2G, Hepascore). Direct biomarker scores were calculated using 2 validated assays for HA (ELISA and radiometric). RESULTS: Using the ELISA assay for HA to calculate the direct panels, all 10 of the biomarkers exhibited comparable overall discriminatory performance (unweighted Obuchowski measure, ordROC 0.92-0.94, P-value>0.05) except AST:ALT ratio and APRI (ordROC 0.86-0.88, P-value<0.05). For the detection of moderate (F2-4) and advanced (F3-4) fibrosis, the AUROC of Fibrometer 2G were significantly higher than AST:ALT ratio and APRI but none of the other biomarkers. Good correlation was observed between the 2 HA assays (intraclass correlation coefficient=0.873) with the ELISA assay exhibiting superior diagnostic performance (ordROC 0.92 vs. 0.88, P-value=0.003). Importantly, the performance of many of the direct biomarkers at their diagnostic thresholds was heavily influenced by the choice of HA assay. CONCLUSIONS: Although many biomarkers exhibited good diagnostic performance for the detection of advancing fibrosis, our results indicate that diagnostic performance may be significantly affected by the selection of individual component assays.

Noninvasive markers of liver fibrosis: on-treatment changes of serum markers predict the outcome of antifibrotic therapy.

AIM: The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established. METHODS: A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study. RESULTS: At 24 months, absolute changes in Ishak fibrosis stage and ELF ranged from -4 to +4 and from -2.41 to +2.68, respectively. Absolute changes in ELF at 12 months were significantly associated with changes in both ELF and histology at 24 months. A model combining both baseline ELF and change of ELF at 12 months could predict the 24-month ELF (R=0.609, P<1×10), a decrease in ELF at 24 months [area under the curve (AUC): 0.80-0.85] and an increase in ELF at 24 months (AUC: 0.81-0.85). Furthermore, a model combining both baseline histologic stage and ELF together with the change of ELF at 12 months could predict 24-month histology (R=0.601, P<1×10, AUC: 0.88-0.92), histologic fibrosis regression (AUC: 0.81-0.84) and progression (AUC: 0.86-0.91). CONCLUSION: Our observations suggest that a change in the serum marker ELF predicts changes in liver fibrosis over a longer period. These data support the use of ELF as a surrogate marker of liver fibrosis evolution in monitoring antifibrotic treatments, thus permitting 'response-guided' therapy by the early identification of patients who will benefit from prolonged treatment.

Role of self-expanding metal stents in the management of variceal haemorrhage: Hype or hope?

Despite the advances of medical, endoscopic and radiological therapy over recent years the mortality rates of acute variceal haemorrhage are still 16%-20% and the medium term outcome has not improved in the last 25 years. Early transjugular intrahepatic portosystemic shunt has proved to be an effective therapy for selected groups of patients with a high risk of re-bleeding and moderate liver disease. However, there is an unmet need for a therapy that can be applied in patients with a high risk of re-bleeding and advanced liver disease either as definitive therapy or as a bridge to permanent therapy. Self-expanding metal stents can be placed without the need for endoscopic or fluoroscopic control and, once in place, will provide effective haemostasis and allow a route for oral fluids and nutrition. They can remain in place whilst liver function recovers and secondary prophylaxis is initiated. We review the results of 6 case series including a total of 83 patients and the first randomised controlled trial of self-expanding metal stents vs balloon tamponade (BT) in the management of refractory variceal haemorrhage. We report that self-expanding metal stents provide effective haemostasis and perform better than BT in refractory bleeding, where they are associated with fewer complications. Whilst the most effective place for self-expanding metal stents in the management algorithm needs to be determined by further randomised controlled trials, currently they provide an effective alternative to BT in selected patients.