CLIF-C AD score predicts survival benefit from pre-emptive TIPS in individuals with Child-Pugh B cirrhosis and acute variceal bleeding.

Background & Aims: Among individuals with Child-Pugh B cirrhosis and acute variceal bleeding (AVB), the Baveno VII workshop recommended pre-emptive TIPS in those with a Child-Pugh score of 8-9 and active bleeding at initial endoscopy (Child B8-9 + AB criteria). Nevertheless, whether this criterion is superior to the CLIF-Consortium acute decompensation score (CLIF-C ADs) remains unclear. Methods: Data on 1,021 consecutive individuals with Child-Pugh B cirrhosis and AVB from 13 university hospitals in China who were treated with pre-emptive TIPS (n = 297) or drug plus endoscopic treatment (n = 724) between 2010 to 2019 were retrospectively analysed. A competing risk regression model was used to compare the outcomes between the two groups after adjusting for confounders. The concordance-statistic for benefit (c-for-benefit) was used to evaluate a models' ability to predict treatment benefit (risk difference between treatment groups). Results: Pre-emptive TIPS was associated with reduced mortality compared to drug plus endoscopic treatment (adjusted hazard ratio 0.62, 95% CI 0.44 to 0.88). A higher baseline CLIF-C AD score was associated with greater survival benefit (i.e., larger absolute mortality risk reduction). After adjusting for confounders, a survival benefit was observed in individuals with CLIF-C ADs ≥48 or Child-Pugh B8-9 with active bleeding, but not in those with CILF-C ADs <48, no active bleeding or Child-Pugh B7 with active bleeding. The c-for-benefit of CILF-C ADs for predicting survival benefit was higher than that of Child B8-9+AB criteria. Conclusions: In individuals with Child-Pugh B cirrhosis and AVB, CLIF-C ADs predicts survival benefit from pre-emptive TIPS and outperforms the Child B8-9+AB criteria. Prospective validation should be performed to confirm this result, especially for other aetiologies of cirrhosis. Impact and implications: In this study, among individuals with Child-Pugh B cirrhosis and acute variceal bleeding, the CLIF-Consortium acute decompensation (CLIF-C AD) score could predict the survival benefit from pre-emptive TIPS, with patients with higher CLIF-C AD scores benefiting more from pre-emptive TIPS. Furthermore, the CLIF-C AD score outperformed the Child B8-9 plus active bleeding criteria in terms of discriminating between those who obtained more benefit vs. less benefit from pre-emptive TIPS. Depending on prospective validation, the CLIF-C AD score could be used as the model of choice to determine who should undergo pre-emptive TIPS.

Overview of Complications in Cirrhosis.

Background: Cirrhosis is the outcome of chronic liver disease of any etiology due to progressive liver injury and fibrosis. Consequently, cirrhosis leads to portal hypertension and liver dysfunction, progressing to complications like ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, cirrhotic cardiomyopathy, sarcopenia, hepatocellular carcinoma, and coagulation disorders. End-stage liver disease leads to an impaired quality of life, loss of social and economic productivity, and reduced survival. Methods: This narrative review explains the pathophysiology of complications of cirrhosis, the diagnostic approach and innovative management, with focus on data from India. A comprehensive literature search of the published data was performed in regard with the spectrum, diagnosis, and management of cirrhosis and its complications. Results: There is a change in the epidemiology of metabolic syndrome, lifestyle diseases, alcohol consumption and the spectrum of etiological diagnosis in patients with cirrhosis. With the advent of universal vaccination and efficacious long-term viral suppression agents for chronic hepatitis B, availability of direct-acting antiviral agents for chronic hepatitis C, and a booming liver transplantation programme across the country, the management of complications is essential. There are several updates in the standard of care in the management of complications of cirrhosis, such as hepatorenal syndrome, hepatocellular carcinoma, and hepatic encephalopathy, and new therapies that address supportive and palliative care in advanced cirrhosis. Conclusion: Prevention, early diagnosis, appropriate management of complications, timely transplantation are cornerstones in the management protocol of cirrhosis and portal hypertension. India needs improved access to care, outreach of public health programmes for viral hepatitis care, health infrastructure, and disease registries for improved healthcare outcomes. Low-cost initiatives like immunization, alcohol cessation, awareness about liver diseases, viral hepatitis elimination, and patient focused decision-making algorithms are essential to manage liver disease in India.

Where does TIPS fit in the management of patients with cirrhosis?

In this review, we summarise the current knowledge on the indications and contraindications of transjugular intrahepatic portosystemic shunt (TIPS) placement for the treatment of the complications of portal hypertension in cirrhosis, specifically variceal haemorrhage and ascites. Moreover, we discuss the role of TIPS for the treatment of portal vein thrombosis (PVT) and the prevention of complications after extrahepatic surgery ('preoperative TIPS') in patients with cirrhosis. The position of TIPS in the treatment hierarchy depends on the clinical setting and on patient characteristics. In acute variceal haemorrhage, preemptive TIPS is indicated in patients at a high risk of failing standard therapy, that is those with a Child-Pugh score of 10-13 points or Child-Pugh B with active bleeding at endoscopy, although the survival benefit in the latter group still remains to be established. Non-preemptive TIPS is a second-line therapy for the prevention of recurrent variceal haemorrhage and for the treatment of ascites. Of note, TIPS may also improve sarcopenia. Contraindications to TIPS placement, independent of clinical setting, include very advanced disease (Child-Pugh >13 points), episodes of recurrent overt hepatic encephalopathy without an identifiable precipitating factor, heart failure, and pulmonary hypertension. In patients with PVT, TIPS placement not only controls complications of portal hypertension, but also promotes portal vein recanalisation. Although the severity of portal hypertension correlates with poor outcomes after extrahepatic surgery, there is no evidence to recommend preoperative TIPS placement.

Granulocyte Colony-Stimulating Factor Use in Decompensated Cirrhosis: Lack of Survival Benefit.

BACKGROUND: Granulocyte colony-stimulating factor (GCSF) has been utilized in decompensated cirrhosis (DC) for improving transplant-free survival (TFS). Data from multiple centers are conflicting with regard to patient outcomes. In this retrospective study, we present our 'real-world experience' of GCSF use in a large group of DC. METHODS: From September 2016 to September 2018, 1231 patients with cirrhosis were screened, of which 754 were found to have decompensation(s). Seventy-three patients with active ascites, jaundice, or both completed GCSF treatment (10 mcg/kg per day for 5 days, followed by 5 mcg/kg/day once every third day for total 12 doses). Per-protocol analysis (n = 56) was performed to study clinical events, liver disease severity, and outcomes at 3, 6, and 12 months after treatment. Modified intention-to-treat (mITT, n = 100) analysis was performed to study overall survival at 180 days. Outcomes were compared with a matched historical control (HC) group (n = 24). RESULTS: Nine (16%, n = 56), 24 (43%, n = 56), and 36 (75%, n = 48) patients died at 3, 6, and 12-month follow-up after GCSF. The commonest cause of death was sepsis (53%) followed by progressive liver failure (33%). Nine percent of patients developed hepatocellular carcinoma on follow-up at the end of 1 year. Acute variceal bleeds, overt hepatic encephalopathy, intensive unit admissions, and liver disease severity scores were higher after treatment at the end of 1 year. The Child-Pugh score >11 and model for end-stage liver disease-sodium score >25 and > 20 predicted worse outcomes at all time points and at 6 and 12 months after GCSF, respectively. Compared to a matched HC group, patients receiving GCSF had higher mortality (75% vs 46%, P = 0.04) at one year. mITT analysis revealed poor overall survival at 6 months compared to HCs (48% vs 75%, P = 0.04). CONCLUSION: Survival in DC was shorter than what was expected in the natural history of the disease after GCSF use.

Addition of Somatostatin After Successful Endoscopic Variceal Ligation Does not Prevent Early Rebleeding in Comparison to Placebo: A Double Blind Randomized Controlled Trial.

BACKGROUND: Efficacy of endoscopic sclerotherapy in controlling acute variceal bleeding is significantly improved when vasoactive drug is added. Endoscopic variceal ligation (EVL) is superior to sclerotherapy. Whether efficacy of EVL will also improve with addition of somatostatin is not known. We compared EVL plus somatostatin versus EVL plus placebo in control of acute variceal bleeding. METHODS: Consecutive cirrhotic patients with acute esophageal variceal bleeding were enrolled. After emergency EVL, patients were randomized to receive either somatostatin (250 mcg/hr) or placebo infusion. Primary endpoint was treatment failure within 5 days. Treatment failure was defined as fresh hematemesis ≥2 h after start of therapy, or a 3 gm drop in Hb, or death. RESULTS: 61 patients were enrolled (EVL plus somatostatin group, n = 31 and EVL plus placebo group, n = 30). The baseline characteristics were similar. Within the initial 5-day period, the frequency of treatment failure was similar in both the groups (EVL plus somatostatin group 8/31 [26%] versus EVL plus placebo group 7/30 [23%]; P = 1.000). The mortality was also similar in the two groups (3/31 [10%] vs. 3/30 [10%]; P = 1.000). Baseline HVPG ≥19 mm Hg and active bleeding at index endoscopy were independent predictors of treatment failure. CONCLUSIONS: Addition of somatostatin infusion to EVL therapy does not offer any advantage in control of acute variceal bleeding or reducing mortality. The reason for this may be its failure to maintain sustained reduction in portal pressure for five days. Active bleeding at index endoscopy and high baseline HVPG should help choose early alternative treatment options. Trial registered with ClincalTrials.gov vide NCT01267669.