Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis.

BACKGROUND & AIMS: Patients with decompensated cirrhosis have significantly reduced survival without liver transplantation. Granulocyte colony-stimulating factor (G-CSF) has been shown to increase survival in patients with acute-on-chronic liver failure, and erythropoietin promoted hepatic regeneration in animal studies. We performed a double-blind, randomized, placebo-controlled trial to determine whether co-administration of these growth factors improved outcomes for patients with advanced cirrhosis. METHODS: In a prospective study, consecutive patients with decompensated cirrhosis seen at the Institute of Liver and Biliary Sciences, New Delhi (from May 2011 through June 2012) were randomly assigned to groups given subcutaneous G-CSF (5 µg/kg/d) for 5 days and then every third day (12 total doses), along with subcutaneous darbopoietin α(40 mcg/wk) for 4 weeks (GDP group, n = 29), or only placebos (control group, n = 26). All patients also received standard medical therapy and were followed for 12 months. Histology was performed on liver biopsies. The primary end point was survival at 12 months. RESULTS: Baseline characteristics of patients were comparable; alcohol intake was the most common etiology of cirrhosis. A higher proportion of patients in the GDP group than controls survived until 12 months (68.6% vs 26.9%; P = .003). At 12 months, Child-Turcotte Pugh scores were reduced by 48.6% in the GDP group and 39.1% in the control group, from baseline (P = .001); Model for End Stage Liver Disease scores were reduced by 40.4% and 33%, respectively (P = .03). The need for large-volume paracentesis was significantly reduced in GDP group, compared with controls (P < .05). A lower proportion of patients in the GDP group developed septic shock (6.9%) during follow-up compared with controls (38.5%; P = .005). No major adverse events were observed in either group. CONCLUSIONS: In a single-center randomized trial, a significantly larger proportion of patients with decompensated cirrhosis given a combination of G-CSF and darbopoietin α survived for 12 months more than patients given only placebo. The combination therapy also reduced liver severity scores and sepsis to a greater extent than placebo. Clinicaltrials.gov ID: NCT01384565.

HPi: A Novel Parameter to Predict Graft-related Outcome in Adult Living Donor Liver Transplant.

BACKGROUND: Portal hyperperfusion is frequently associated with early allograft dysfunction (EAD). It is imperative to identify patients who would require portal inflow modulation. We aimed to identify factors associated with hyperperfusion-related graft injury and develop a predictive index for the same. METHODS: Prospectively maintained database was queried to identify 135 adult living donor liver transplant recipients between September 2016 and July 2020. According to the calculated sample size, 96 patients were randomly selected for "test cohort". The remaining 39 patients made the "validation cohort." EAD was defined according to the A2ALL study. "Hyperperfusion index (HPi)," defined as posttransplant portal pressure gradient (ΔPpost)/graft-to-recipient splenic volume ratio (GRSVR), was devised on the basis of laws of flow dynamics and regression analysis. RESULTS: Overall, 40 patients (29.6%) had EAD, six 90-d mortalities (4.4%) were attributable to EAD. In the test cohort, EAD patients (n = 29, 30.2%) had lower GRSVR (1.00 versus 2.22, P < 0.001), higher ΔPpost (14.8 versus 11.9, P = 0.004), and HPi (20.89 versus 8.67, P < 0.001). Multivariate analysis revealed GRSVR, ΔPpost, and HPi as significant factors to predict EAD. Receiver operating characteristic determined cutoff of HPi ≥9.97 could predict EAD with sensitivity of 90% and specificity of 73% (F-score = 0.712). HPi ≥16.25 predicted 90-d mortality with sensitivity of 100% and specificity of 78.9%. Patients with higher HPi had delayed graft-related recovery. Non-EAD patients had a higher 1-y (96% versus 79%) and 2-y (88% versus 79%) survival. The cutoff of HPi was validated well in the validation cohort (F-score = 0.645) (Hosmer-Lemeshow test, P = 0.89). CONCLUSIONS: While predicted GRSVR may help identify at-risk patients preoperatively, intraoperatively calculated HPi is more accurate in identifying patients who would require portal inflow modulation. Achieving an HPi below target cutoff significantly decreases the risk of EAD even in low-GRSVR patients.

Recurrent Hepatic Artery Thrombosis Following Living Donor Liver Transplant as Sequelae of SARS-CoV-2 Infection-a Case Report.

As the second wave of COVID-19 disease is gripping the globe, liver transplant centers are increasingly receiving patients recovered from SARS-CoV-2 infection in recent few weeks. Unexpected complications in these patients are increasingly being recognized. We performed liver transplantation on a 51-year-old gentleman with decompensated liver disease 23 days after recovering from a mild SARS-CoV-2 infection. Surprisingly, despite massive blood loss and a prolonged anhepatic phase, his thromboelastographic (TEG) parameters persistently revealed hypercoagulability. After a brief uneventful early post-operative period, he developed hepatic arterial thrombosis on the 14th post-operative day, and again after 4 days, both of which required surgical intervention. Following discharge, the artery was thrombosed again which was only picked up when he developed a cholangiolar abscess, leading to graft loss necessitating re-transplantation. There is a lot of evidence suggesting that patients with SARS-CoV-2 infection tend to be hypercoagulable. We believe that this hypercoagulability might have played a significant role in the development of hepatic arterial thrombosis and eventual graft loss in this patient. This highlights the importance of revisiting anticoagulation protocols in liver transplant recipients recovered from COVID-19 and base them on TEG rather than routine parameters such as INR and APTT, which are routinely deranged in such patients.

Intramural hematoma of duodenum: An unusual complication after endoscopic therapy for a bleeding peptic ulcer.

Intramural hematoma of duodenum (IDH) is a relatively unusual complication associated with endoscopic treatment of bleeding peptic ulcer. This unusual condition is usually seen in children following blunt trauma to the abdomen. We describe here a case of IDH occurring following endoscopic therapy for bleeding duodenal ulcer in an adult patient with end-stage renal disease. The hematomas appeared on the second day of endoscopic intervention, caused transient duodenal obstruction and resolved spontaneously with conservative treatment in a week.