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Coronavirus disease-2019 (COVID-19) has led to a temporary suspension of liver transplant activity across the world and the remodeling of care for patients on the waiting list and transplant recipients with the increasing use of remote consultations. Emerging evidence shows that patients with more advanced liver disease are at increased risk of severe COVID-19 and death, whereas transplant recipients have similar risk with the general population which is mainly driven by age and metabolic comorbidities. Tacrolimus immunosuppression might have a protective role in the post-transplant population. Vaccines that have become rapidly available seem to be safe in liver patients, but the antibody response in transplant patients is likely suboptimal. Most transplant centers were gradually able to resume activity soon after the onset of the pandemic and after modifying their pathways to optimize safety for patients and workforce. Preliminary evidence regarding utilizing grafts from positive donors and/or transplanting recently recovered or infected recipients under certain circumstances is encou raging and may allow offering life-saving transplant to patients at the greatest need. This review summarizes the currently available data on liver trans plantation in the context of a major pandemic and discusses areas of uncertainty and future challenges. Lessons learnt from the COVID-19 pandemic might provide invaluable guidance for future pandemics.

Background and Aims A 40% risk of disease recurrence post-liver transplantation (LT) for autoimmune hepatitis (AIH) has been previously reported. Risk factors for recurrence and its impact on long-term patient outcome are poorly defined. We aimed to assess prevalence, time to disease recurrence, as well as patient and graft survival in patients with recurrent AIH (rAIH) versus those without recurrence. Methods Single-center retrospective study of adult recipients who underwent LT for AIH between January 2007 and December 2017. Patients with AIH overlap syndromes were excluded. Results A total of 1436 LTs were performed during the study period, of whom 46 (3%) for AIH. Eight patients had AIH overlap syndromes and were excluded. Patients were followed up for 4.4 ± 3.4 years and mean age at LT was 46.8 years. Average transplant MELD (Model for End-Stage Liver Disease) score was 24.9. About 21% of patients (8 of 38) were transplanted for acute onset of AIH; 66% of patients (n = 25) received a deceased donor liver graft, and 34% a living donor organ. rAIH occurred in 7.8% (n = 3/38) of recipients. Time to recurrence was 1.6, 12.2 and 60.7 months. Patient and graft survival in patients without recurrence was 88.6% and 82.8% in 5 years, whereas in those with rAIH, it was 66.7%, respectively. Conclusion Although AIH recurs post-LT, our data indicate a lower recurrence rate when compared to the literature and excellent patient and graft survival.

Ascites occurs in up to 70% of patients during the natural history of cirrhosis. Management of uncomplicated ascites includes sodium restriction and diuretic therapy, whereas that for refractory ascites (RA) is regular large-volume paracentesis with transjugular intrahepatic portosystemic shunt being offered in appropriate patients. Renal impairment occurs in up to 50% of patients with RA with type 1 hepatorenal syndrome (HRS) being most severe. Liver transplant remains the definitive treatment of eligible candidates with HRS, whereas combined liver and kidney transplant should be considered in patients requiring dialysis for more than 4 to 6 weeks or those with underlying chronic kidney disease.

Ascites commonly complicates cirrhosis, becoming refractory to treatment with diuretics and sodium restriction in approximately 10% of patients. Pathogenesis of refractory ascites (RA) is multifactorial, the common final pathway being renal hypoperfusion and avid sodium retention. Refractory ascites has a negative prognostic implication in the natural history of cirrhosis. Management of RA include sodium restriction and regular large volume paracentesis (LVP) with albumin infusions, preventing paracentesis-induced circulatory dysfunction. In appropriate setting, transjugular intrahepatic porto-systemic shunt (TIPS) can be considered. Ascites clearance with TIPS can lead to nutritional improvement, avoiding sarcopenia. Liver transplantation (LT) remains the definitive treatment for eligible candidates. Areas covered: Our review summarizes current updates on pathogenesis and clinical management of RA including potential future therapeutic options such as the automated slow-flow ascites pump, chronic outpatient albumin infusion and cell-free and concentrated ascites reinfusion therapy. Expert commentary: Standard of care in patients with RA include LVP with albumin replacement and prompt referral for LT where indicated. Other novel therapeutic options on the horizon include automated low-flow ascites pump and cell-free, concentrated albumin reinfusion therapy.

Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.

Background & Aims Mortality of patients who develop acute-on-chronic liver failure (ACLF) is unacceptably high but the predominant mode of cell death is unknown. The aim of this study was to evaluate whether plasma levels of caspase-cleaved cytokeratin M30 (marker of apoptosis) and uncleaved cytokeratin M65 (marker of total cell death) are altered in ACLF patients and relate this to liver histology. Methods Twenty-seven patients with acute decompensation of liver disease were divided into two groups: no-ACLF (n = 11) or ACLF (n−16). Healthy controls (n = 8) and acute liver failure (ALF) patients (n = 10) were also enrolled. Cell death was assessed in plasma using an ELISA kit (M30 and M65). Simultaneous biopsy samples were analysed for M30 and caspase-3 staining. Results Plasma M30 value was significantly elevated in ACLF patients compared with healthy volunteers (P = 0.0001), it was also significantly higher in ACLF patients compared with no-ACLF patients (P = 0.002). M65 levels were higher in ALF compared with ACLF patients (P = 0.002) but the apoptotic index defined by M30/M65 ratio was significantly higher in ACLF patients. Patients with extra-hepatic failure had higher M30 levels compared with patients without organ failure (P = 0.03). M30 staining in liver was more marked in the patients with ACLF and was observed in all the patients that died. Conclusions The results of this study suggest that hepatocyte apoptosis is the predominant mode of cell death in ACLF, which can be identified in the peripheral blood. Further studies are required to validate our findings and to determine whether M30 can be used as a biomarker of apoptosis or as a target for therapy.

Fulminant hepatitis (FH) is a rare and devastating syndrome caused by a variety of hepatic insults. It characterized by severe metabolic derangements, neurologic complications and ultimately, multiorgan failure. Liver transplantation is the gold standard therapy for patients with irreversible FH. The major areas of current research in this field include the development of: hepatic support devices, strategies to accelerate hepatic regeneration and criteria for accurate prognostic classification of patients. This review aims to focus on the definitions, aetiologies and management strategies for FH.

Background A 21-year-old white male with a 3-year history of back pain presented with a 6-month history of weight loss (without significant gastrointestinal symptoms), lethargy and left hip pain, and diarrhea that had lasted 4 days. Investigations Barium follow-through, upper and lower gastrointestinal endoscopy and biopsies, capsule enteroscopy, CT of the chest and abdomen, measurement of the concentration of fecal calprotectin, intestinal absorption permeability test and wireless capsule endoscopy. Diagnosis Ankylosing spondylitis associated with ileitis of spondylarthropathy. Management Sulfasalazine and elemental diet, steroids, physiotherapy and bilateral hip replacement.

See Article, pages 1070–1079 Although the outcome of acute liver failure (ALF) has improved due to developments in the general intensive care techniques, mortality rates without transplantation in patients who fulfil poor prognostic criteria are still in excess of 80%. Besides N-acetylcysteine, there are no specific treatment options for ALF that occurs on the background of acetaminophen (APAP) toxicity. Also, strategies to limit progression of acute liver injury in patients who are progressing to ALF remain an unmet need. Further difficulties in the management of patients with ALF are the lack of biomarkers that may indicate progression of liver failure early as decision making regarding listing for transplantation in patients with ALF is challenging. At present, the criteria that are used to list patients for urgent transplantation lack sensitivity [1]. Therefore, the paper by Antoine and colleagues [2] in the present issue of the Journal is welcome as it starts to address

The short-term mortality of cirrhotic patients who develop renal dysfunction remains unacceptably high, and as such the treatment of this condition is an unmet need. Although features of kidney injury are well recognized in these patients, the pathophysiology is complex and not completely understood. Improved understanding of the pathophysiological mechanisms involved in renal dysfunction occurring on a background of cirrhosis is key to developing effective treatment strategies to improve survival. Renal dysfunction due to hepatorenal syndrome (HRS) is characteristic of cirrhosis. Our current understanding is that HRS is functional in nature and occurs as a consequence of hemodynamic changes associated with portal hypertension. However, there is evidence in the literature suggesting that, histologically, the kidneys are not always normal in the vast majority of patients who present with renal dysfunction on the background of cirrhosis. Furthermore, there is emerging data implicating nonvasomotor mechanisms in the pathophysiology of renal dysfunction in cirrhosis. This mini-review aims to present the evidence suggesting that factors other than hemodynamic dysregulation have an important role in the development of this major complication for patients with progressive cirrhosis.