Early cirrhosis and a preserved bone marrow niche favour regenerative response to growth factors in decompensated cirrhosis.

BACKGROUND: Exogenous growth factor-mobilized bone marrow (BM) stem cells have shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in granulocyte-colony stimulating factor (G-CSF)-mobilized stem cell therapy, possible mechanisms of regeneration and predictive factors of regenerative response. METHODS: Sixty consecutive DC patients received either G-CSF with EPO (Group A; n = 30) or G-CSF and placebo (Group B; n = 30) for 2 months and were carefully followed up for 1 year. Baseline and post-treatment liver biopsy, BM biopsy and BM aspirate were analysed for fibro-inflammatory and regenerative response and BM hematopoietic reservoir. RESULTS: Addition of EPO to G-CSF showed a significant improvement in Child-Pugh score (P = 0.03) and MELD score (P = 0.003) as compared to G-CSF alone, with reduction in mortality (16.6% vs 36.7%, P = 0.09). The combination arm also demonstrated a decreased incidence of acute kidney injury (P < 0.001), encephalopathy (P = 0.005) and refilling of ascites (P = 0.03). Compared to monotherapy, it increased CD163+ macrophages (P = 0.013), Ki67+ index (P < 0.001) with decrease in α-SMA levels (P < 0.001) in liver tissue. The response was better with grade 1 and 2 than with grade 3 ascites; Child B cirrhosis and MELD < 16. Non-responders had lower hematopoietic stem cells (HSCs) at baseline. On multivariate analysis, the liver disease severity (MELD < 16) and a relatively preserved BM (BM-HSCs > 0.4) predicted therapeutic response (AUROC = 0.82). CONCLUSIONS: Early DC (MELD < 16) patients with mild-moderate ascites and those with a healthy cellular baseline BM respond better to growth factor therapy. Addition of EPO to G-CSF provides better regenerative response than G-CSF monotherapy.

Impact of family history of metabolic traits on severity of non-alcoholic steatohepatitis related cirrhosis: A cross-sectional study.

BACKGROUND & AIMS: Familial aggregation of metabolic traits with fatty liver disease is well documented. However, there is scarcity of data regarding such association with non-alcoholic steatohepatitis (NASH)-related cirrhosis. This study was aimed to explore the association of family history of metabolic traits with severity of cirrhosis. METHODS: In a cross-sectional study, all consecutive patients with NASH-related cirrhosis presenting to our tertiary care centre were included. Family history, personal history, demographic characteristics, medical history, anthropometric measurements and laboratory data were recorded. RESULTS: Of the 1133 cirrhotics (68.1% males, age 51.4±10.9 years); 779 (68.8%) had family history for metabolic traits. These patients had lower age at diagnosis (45.4±10.6 vs 49.6±11.2 years), higher Child-Turcotte-Pugh (CTP) score (7.8±1.9 vs 6.6±1.5), higher model for end stage liver disease (MELD) score (12.9±6.1 vs 10.9±4.1) and more incidence of decompensation in the form of ascites (46.3% vs 25.7%), jaundice (12.1% vs 6.2%) and hepatic encephalopathy (26.1% vs 11.0%). Patients with family and personal history of metabolic traits, had an increased risk of an early diagnosis of cirrhosis at<45 years of age (OR: 3.1, 95% CI 2.1-4.4), CTP≥10 (OR: 4.6, 95% CI 2.3-9.1), MELD>15 (OR: 6.6, 95% CI 3.8-11.5) with ≥1 features of decompensation (OR: 4.2, 95% CI 2.9-6.1). Family history of diabetes alone, also had higher risk of cirrhosis with MELD>15 (OR: 4.3, 95% CI 2.4-5.3, P<.001). CONCLUSION: Family and personal history of metabolic traits are associated with early age at diagnosis of cirrhosis with more severity and decompensation and so, has a prognostic importance in NASH-related cirrhotics.

A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock.

BACKGROUND & AIMS: The choice of vasopressor for treating cirrhosis with septic shock is unclear. While noradrenaline in general is the preferred vasopressor, terlipressin improves microcirculation in addition to vasopressor action in non-cirrhotics. We compared the efficacy and safety of noradrenaline and terlipressin in cirrhotics with septic shock. PATIENTS AND METHODS: Cirrhotics with septic shock underwent open label randomization to receive either terlipressin (n=42) or noradrenaline (n=42) infusion at a titrated dose. The primary outcome was mean arterial pressure (MAP) >65 mm Hg at 48 h. RESULTS: Baseline characteristics were comparable between the terlipressin and noradrenaline groups.SBP and pneumonia were major sources of sepsis. A higher proportion of patients on terlipressin were able to achieve MAP >65 mm of Hg (92.9% vs 69.1% P=.005) at 48 h. Subsequent discontinuation of vasopressor after hemodynamic stability was better with terlipressin (33.3% vs 11.9%, P<.05). Terlipressin compared to noradrenaline prevented variceal bleed (0% vs 9.5%, P=.01) and improved survival at 48 h (95.2% vs 71.4%, P=.003). Percentage lactate clearance (LC) is an independent predictor of survival [P=.0001, HR=3.9 (95% CI: 1.85-8.22)] after achieving the target MAP.Therapy related adverse effect were comparable in both the arms (40.5% vs 21.4%, P=.06), mostly minor (GradeII-88%) and reversible. CONCLUSIONS: Terlipressin is as effective as noradrenaline as a vasopressor in cirrhotics with septic shock and can serve as a useful drug. Terlipressin additionally provides early survival benefit and reduces the risk of variceal bleed. Lactate clearance is a better predictor of outcome even after achieving target MAP, suggesting the role of microcirculation in septic shock.

First Report of Two-stage Living Donor Liver Transplantation to Avoid Futility and Ensure Double Equipoise in Acute Liver Failure Complicated by Toxic Liver Syndrome.

Acute hepatic failure may occasionally be complicated by toxic liver syndrome. Emergency hepatectomy for stabilization followed by delayed graft implantation is a recognized strategy in such cases in the setting of deceased donor liver transplantation. Living donor liver transplantation adds additional complexity to this scenario as the donor liver is a directed donation and failure to stabilize the patient after emergency hepatectomy can lead to a futile live donor hepatectomy, hepar-divisum, or an orphan graft. We report a case where the two-stage strategy was utilized to circumvent this situation. A patient with toxic liver syndrome underwent emergency hepatectomy and was closely monitored in the operating theater. A live donor hepatectomy was started after the recipient demonstrated cardiovascular and neurological stabilization. Graft implantation was completed after an anhepatic period of 9.45 h. To our knowledge, this is the first reported instance of using the two-stage strategy in living-donor-liver-transplantation for toxic liver syndrome to prevent futile donor surgery and achieve double equipoise.

Palliative Care for Patients with End-Stage Liver Disease.

End-stage liver disease (ESLD) is the culmination of progression of chronic liver disease to cirrhosis, decompensation, and chronic liver failure, featuring portal hypertension or hepatocellular failure-related complications. Liver transplantation offers improved long-term survival for these patients but is negatively influenced by donor availability, financial constraints in developing countries, active substance abuse, progression of disease or malignancy on wait-list, sepsis and extrahepatic organ involvement. In this context, palliative care (PC), an interdisciplinary medical practice that aim to prevent and relieve suffering, offers best possible quality of life and is not limited to end-of-life care. It also encompasses achievable goals such as symptom control and aggressive disease-modifying treatments or interventions that beneficially alter the natural course of the disease to offer curative intend. In this narrative review, we discuss the prognostic factors that define disease course in ESLD, various indications and challenges in PC for advanced cirrhosis and management options for major symptom burden in patients with ESLD based on evidence-based best practice.

Role of N-acetyl Cysteine in Post-transarterial Chemoembolization Transaminitis in Hepatocellular Carcinoma: A Single-center Experience.

BACKGROUND: Transarterial chemoembolization (TACE) is the most common locoregional therapy for hepatocellular carcinoma (HCC). Postembolization syndrome is not an uncommon complication. At present, there is no specific treatment for management of this complication. We aimed to study the role of N-acetyl cysteine (NAC), an antioxidant, in management of this complication. METHODS: In a prospective observational study, consecutive patients with HCC undergoing TACE from January 2016 to January 2017 were included. Patients with postembolization syndrome, defined as an elevation of transaminase levels more than 3-4 times the upper limit of normal, were administered intravenous NAC for 72 h (150 mg/kg for 1 h, then 12.5 mg/kg/h for 4 h, and continuous infusion 6.25 mg/h for the remaining 67 h). The other group received only supportive standard of care. The primary end point was reduction in post-TACE transaminitis. RESULTS: Of 112 patients with HCC, 53 (47.3%) received NAC. The majority were cirrhotics in both the groups. Both groups were well matched in demographic, laboratory, and tumor characteristics. In the NAC group, there was significant reduction in Aspartate transaminase (AST) and Alanine transaminase (ALT) levels from day 1 to day 3 (p = 0.000) compared with the non-NAC group, with no significant change in bilirubin or international normalized ratio levels. The duration of hospital stay was similar in both the groups. None had any major adverse events to NAC. CONCLUSION: This is a prospective, single-center experience, showing that early initiation of N-acetyl cysteine in those with post-TACE embolization syndrome reduces the transaminase level significantly.

Prevalence of Hepatitis B and C Among Prison Inmates in India: A Systematic Review and Meta-Analysis.

Viral hepatitis is still considered a major cause of the burden of disease in India. It is the most common cause of cirrhosis and liver cancer. Prisoners are one of the groups at most risk for hepatitis. This study aimed to estimate the pooled estimates of the prevalence of hepatitis B and C among prisoners in India. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for study selection. The extensive search was done through databases of PubMed, Embase, and Google Scholar. All cross-sectional studies conducted to find the prevalence of hepatitis B and C among prison inmates in India published till June 2020 were screened and included in this meta-analysis. The analysis was conducted using the random-effects model. The heterogeneity was estimated using the I2 indicator. After extracting the required data, the meta-analysis was performed using the software Stata, version 12 (StataCorp LLC, College Station, Texas). The study is registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration no: CRD42020185137). Out of a total of 970 articles searched through the database of PubMed, Embase, and Google Scholar, five studies that met the inclusion criteria were included and analyzed. Hepatitis B and C prevalence were given in four studies each. The results showed that the overall prevalence of hepatitis B and C in prisoners was 8% (95% CI: 4-12) and 7% (95% CI: 1-13). The studies show high heterogeneity with no evidence of publication bias. The prevalence of hepatitis B and C among male prisoners was 4.48% (95% CI: 3.64%-5.32%) and 6.35% (95% CI: 5.48%-7.23%), respectively, while the prevalence among female prisoners was 1.53% (95% CI: 0.31-2.75) and 2.10% (95% CI: 0.28-3.93), respectively. The study findings show a high prevalence of hepatitis B and C in prisoners, which is of particular concern. Appropriate and effective interventions to reduce the transmission of hepatitis B and C in prisons are essential.