Intragastric Balloon in Obese Compensated Nonalcoholic Steatohepatitis Cirrhosis Patients Is Safe and Achieves Significant Weight Reduction at 6-Months.

BACKGROUND AND STUDY AIMS: Weight reduction is the mainstay treatment for Nonalcoholic steatohepatitis (NASH). intragastric balloon (IGB) placement has proven benefit in terms of weight reduction. The aim of the present study is to assess the safety and efficacy of IGB placement in compensated NASH cirrhosis. PATIENTS AND METHODS: Nonalcoholic steatohepatitis cirrhosis patients with CTP ≤ 7, BMI of > 30, and who were unable to achieve weight reduction with lifestyle modification in past 3 months were prospectively enrolled. Spatz3™ adjustable gastric balloon was placed endoscopically. Primary objective was to determine efficacy in weight loss at 6 months, with secondary objectives of reduction in hepatic venous pressure gradient (HVPG), liver fat (controlled attenuation parameter, CAP), liver stiffness measurement (LSM) and clinical events as well as the tolerability and adverse events due to IGB placement. RESULTS: Altogether 56 cirrhosis patients, with a baseline BMI of 35.24 ± 3.92 and a CTP score of 6.27 ± 1.28 underwent IGB placement. The absolute weight reduction achieved was 15.88 kg (- 16.46%) and reduction in BMI was - 10.1% at 6 months. The percentage total body weight loss of ≥ 10% was achieved in 31 (55.35%) patients. The reduction in HVPG at 6-months was 11.12% (n = 16, 14.18 ± 2.12 to 12.60 ± 1.67 mmHg). The mean reduction in LSM was 28.6% and in CAP was 10.09%. Three (5.36%) patients required removal of IGB before 6-months due to persisting vomiting. No patient developed new-onset decompensation or any serious adverse event. CONCLUSION: IGB placement is a safe, well tolerated and effective option for reduction in weight and portal pressure in compensated obese cirrhosis patients. TRIAL REGISTRY: Clinicaltrails.gov identifier no: NCT03753438.

Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients.

BACKGROUND AND AIMS: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. METHODS: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. RESULTS: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality. CONCLUSIONS: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.

Gastrointestinal dysmotility is common in cirrhosis and higher incidence in critically ill patients. Promotility drugs are the first line of medication especially in ICU patients. In our study, we found that feed intolerance is present in nearly one in five critically ill cirrhosis and is associated with higher mortality. Patients who achieve resolution had an improved short-term survival. Prokinetic medications are safe in critically ill cirrhosis and help in early resolution of feed intolerance. Feed intolerance in critically ill cirrhosis should be recognized as an organ dysfunction and approaches for prevention and early diagnosis of feed intolerance could help in improving the outcomes in critical illness.

Assessment of small intestinal bacterial overgrowth in chronic pancreatitis patients using jejunal aspirate culture and glucose hydrogen breath test.

BACKGROUND: A subset of chronic pancreatitis patients respond poorly to pancreatic enzyme replacement therapy. Small intestinal bacterial overgrowth (SIBO) is considered to be one of the major reasons for this poor response. Previous studies have reported a wide range of prevalence of SIBO in patients with chronic pancreatitis. We aimed to assess the prevalence of SIBO in chronic pancreatitis using quantitative jejunal aspirate culture and glucose hydrogen breath test (GHBT). The sensitivity and specificity of GHBT for the diagnosis of SIBO in chronic pancreatitis were also estimated. METHODS: Newly diagnosed chronic pancreatitis patients were recruited into the study. A detailed history and relevant laboratory tests were done. All patients underwent an endoscopy and jejunal fluid aspiration for bacterial cultures and GHBT to detect SIBO. The results of GHBT were compared with jejunal fluid aspirate culture. RESULTS: The jejunal aspirate culture was positive in 18/48 (37.5%) patients while the GHBT showed that 14/48 (29%) patients had SIBO. The sensitivity, specificity, positive and negative predictive value of GHBT in our study was 44.4, 80, 57.14 and 70.59%, respectively. CONCLUSIONS: SIBO is not uncommon in chronic pancreatitis patients. One-third of our study population had SIBO. GHBT has low sensitivity but had high specificity in the diagnosis of SIBO in chronic pancreatitis.

SX-Ella Stent Danis Effectively Controls Refractory Variceal Bleed in Patients with Acute-on-Chronic Liver Failure.

BACKGROUND AND AIMS: Almost 10% of bleeding episodes are refractory to combination of vasoactive agent and endotherapy, and are associated with a mortality up to 50%. Severity of liver disease and high portal pressure are mainly responsible for it. TIPS cannot be used in these patients due to high MELD score. We aimed to evaluate the efficacy of self-expandable DE stents for control of refractory variceal bleeds in patients with ACLF. METHODS: Acute-on-chronic liver failure patients (n = 88, mean age 47.3 ± 10.9 years) with refractory variceal bleeds received either DE stent (Gr. A, n = 35) or continued with repeat endotherapy and vasoactive drug (Gr.B, n = 53). Matching by propensity risk score (PRS) was done to avoid selection bias. Competing risk Cox regression analysis was done to identify event-specific, i.e., gastrointestinal bleed-related death. RESULTS: Majority (78.4%) of patients were alcoholic with MELD score of 45.9 ± 20.1. Control of initial bleeding was significantly more in the DE stent group as compared to controls in both pre-match (89 vs. 37%; p < 0.001) and PRS-matched cohorts (73 vs. 32%; 0.007). Further, bleed-related death was also significantly lower in DE group as compared to controls in both pre-match (14 vs. 64%; p = 0.001) and PRS-matched cohorts (6 vs. 56%; p = 0.001). In a multivariate competing risk Cox model, patients who underwent DE stenting had reduced mortality in both pre-match (p = 0.04, HR 0.36, 95% CI 0.13-0.96) and PRS-matched cohorts (p < 0.001, HR 0.21, 95% CI 0.08-0.51). CONCLUSIONS: Self-expandable DE stents are very effective in control of refractory variceal bleeding and reduced mortality in patients with severe liver failure.

Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.

Endoscopic ultrasound-guided coiling and glue is safe and superior to endoscopic glue injection in gastric varices with severe liver disease: a retrospective case control study.

BACKGROUND/AIMS: Gastric varices (GV) are present in 25% of cirrhotic patients with high rates of rebleeding and mortality. Data on endoscopic ultrasound (EUS)-guided treatment in severe liver disease (model for end stage liver disease sodium [MELD-Na] >18 and Child-Turcotte-Pugh [CTP] C with GV) are scarce. Thus, we performed a retrospective comparison of endoscopic glue injection with EUS-guided therapy in cirrhotic patients with large GV. METHODS: A retrospective study was performed in the tertiary hospitals of India. A total of 80 patients were recruited. The inclusion criteria were gastroesophageal varices type 2, isolated gastric varices type 1, bleeding within 6 weeks, size of GV >10 mm, and a MELD-Na >18. Treatment outcomes and complications of endoscopic glue injection and EUS-guided GV therapy were compared. RESULTS: In this study, the patients' age, sex, liver disease severity (CTP, MELD-Na) and clinical parameters were comparable. The median number of procedures, injected glue volume, complications, and GV obturation were better in the EUS group, respectively. On subgroup analysis of the EUS method (e.g., direct gastric fundus vs. paragastric collateral [PGC] coil placement), PGC coil placement showed decreased coil requirement, less injected glue volume, decreased luminal coil extrusion, and increased successful GV obturation. CONCLUSION: EUS-guided treatment is more efficient and safer, and requires a smaller number of treatment sessions, as compared to endoscopic treatment in severe liver disease patients with large GV. Furthermore, PGC coil placement increases the complete obliteration of GV.

Prevalence of and Factors Associated with Sleep-Wake Abnormalities in Patients with Cirrhosis.

BACKGROUND & AIMS: Sleep-wake abnormalities [poor nighttime sleep and excessive daytime sleepiness (EDS)] are common in patients with cirrhosis. The aim of this study was to assess the prevalence of sleep-wake abnormalities and clinical factors associated with these abnormalities in a group of patients with cirrhosis. METHODS: 1098 patients with cirrhosis [Child Turcotte Pugh (CTP) class A, 22.2%; CTP class B, 29.2% and CTP class C, 48.6%], with either no ascites or mild ascites controlled on diuretics, and no history of or current overt hepatic encephalopathy were included in the study. RESULTS: Poor nighttime sleep and EDS were found in 569 (51.8%) and 489 (44.5%) patients respectively. On multivariate analysis, factors associated with poor nighttime sleep were CTP class C (vs. class A), presence of minimal hepatic encephalopathy (MHE), intermediate or evening type of diurnal preference category (vs. morning type), high risk for obstructive sleep apnea (OSA), diuretic use, presence of major depression, and presence of generalized anxiety disorder (GAD). Factors associated with EDS on multivariate analysis were CTP class B and C (vs. class A), intermediate or evening type of diurnal preference category (vs. morning type), high risk for OSA, presence of major depression, and presence of GAD. CONCLUSIONS: Sleep-wake abnormalities are common in patients with cirrhosis. CTP status, diurnal preference chronotype, risk of OSA, major depression and GAD are associated with both poor nighttime sleep and EDS. MHE and diuretic use are associated with poor nighttime sleep, but not with EDS.

An unusual cause of gastrointestinal bleed in patients with liver cirrhosis.

Acute upper gastrointestinal (UGI) bleeding in cirrhosis has been classically linked to variceal rupture, although peptic ulcer and portal hypertensive gastropathy-related bleed are not uncommon. Gastrointestinal stromal tumour (GIST) is the most common mesenchymal tumour and may also present as UGI bleed; however, there are no reports of GIST presenting as UGI bleed in patients with cirrhosis. Here, we report three cases of GIST who had presented with UGI bleed and were successfully managed with surgical excision and are tolerating imatinib without recurrence.

Case Control Study of Post-endoscopic Variceal Ligation Bleeding Ulcers in Severe Liver Disease: Outcomes and Management.

Background and Aims: The management of post-endoscopic variceal ligation (EVL) bleeding ulcers (PEBUs) is currently based on local expertise and patients liver disease status. The present retrospective study investigated associations between the endoscopic morphology of PEBUs and patient outcomes. Methods: Patients underwent EVL (primary or secondary), from January 2015 to January 2018, in two tertiary care hospitals in India (ILBS New Delhi and Dharamshila Narayana New Delhi). Mortality rates were determined at post-EVL day five and week six. PEBUs were typified based on Jamwal & Sarin classification system as follows: A, ulcer with active spurting; B, ulcer with ooze; C, ulcer base with visible vessel or clot; and D, clean or pigmented base. Results: Of 3854 EVL procedures, 141 (3.6%) patients developed PEBU, and 46/141 (32.6%) suffered mortality. Among the former, the PEBU types A, B, C, and D accounted for 17.7, 26.2, 36.3, and 19.8%, respectively. Of those who died, 39.1, 30.4, 21.7, and 8.8% had PEBU types A, B, C, and D. Treatments included transjugular intrahepatic portosystemic shunts (TIPS), esophageal self-expandable metal stent (SEMS), glue and sclerosant injection, Sengstaken-Blakemore tube placement and liver transplant. On univariate analysis, no correlation with hepatic venous pressure gradient, TIPS placement, size of varices, or number of bands was found. The Model for End-Stage Liver Disease (MELD)-sodium score correlated positively with outcome. After adjusting for MELD-sodium score, mortality was best predicted by type-A ulcer (p = 0.024; OR 8.95, CI 1.34-59.72). Conclusions: PEBU occurred in 3.6% of a large EVL cohort. Stratifying patients based on PEBU type can help predict outcomes, independent of the MELD-sodium score. Classifying PEBUs by endoscopic morphology may inform treatment strategies, and warrants further validation.

Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial.

BACKGROUND/AIMS: The aim of this study was to study the efficacy and safety of zolpidem for sleep disturbances in patients with cirrhosis. METHODS: Fifty-two Child-Turcotte-Pugh (CTP) class A or B cirrhotics with Pittsburgh Sleep Quality Index >5 were randomized to either zolpidem 5 mg daily (n=26) or placebo (n=26) for 4 weeks. RESULTS: The therapy of 4 weeks was completed by 23 patients receiving zolpidem (3 stopped treatment due to excessive daytime drowsiness) and 24 receiving placebo (2 refused to continue the study). In the zolpidem group, after 4 weeks of therapy, there was significant increase in total sleep time (TST) and sleep efficiency compared to baseline and improvement in polysomnographic parameters of sleep initiation and maintenance (i.e., decrease in sleep latency time, decrease in wake time, and decreases in number of arousals and periodic limbs movements per hour of sleep), without any significant change in sleep architecture. CONCLUSION: Four weeks of 5 mg daily zolpidem in CTP class A or B cirrhosis patients with insomnia led to significant increases in TST and sleep efficiency and improvement in polysomnographic parameters of sleep initiation and maintenance without any significant change in sleep architecture.

Endoscopic drainage of obstructed biliary system in altered gastrointestinal anatomy: An experience from a tertiary center in India.

INTRODUCTION: With the advances in imaging and endoscopic technology, scope of endoscopic interventions in biliary obstruction associated with altered gastrointestinal (GI) anatomy has increased. We analyzed our experience on single-balloon enteroscopy and endoscopic ultrasound (EUS)-guided ERCP (SBE-ERCP) and EUS-guided hepatogastrostomy (EUS-HG) in the presence of altered GI anatomy. METHODS: Data of 15 patients (SBE-ERCP in 12, and EUS-HG in 3) over a period of 1 year (April 2016-March 2017) and followed up for 90 to 270 days were retrospectively analyzed. Inclusion criteria were (a) age 18-80 years, (b) fit for anesthesia, (c) intact primary confluence, (d) failed percutaneous transhepatic biliary drainage (PTBD) or difficult EUS-HG (due to poor visualization of intrahepatic ducts due to pneumobilia after PTBD; SBE-ERCP was undertaken in them), and (e) cholangitis without shock. Exclusion criteria were (a) involved or separated primary biliary confluence, (b) shock, (c) unfit for anesthesia, and (d) liver metastasis in the left lobe (EUS-HG). RESULTS: All were symptomatic with pain, jaundice, and cholangitis. The median serum bilirubin and serum alkaline phosphatase (SAP) were 2.8 mg/dL and 273 IU/mL, respectively. SBE-ERCP in 12 and EUS-HG in 3 cases were  done successfully with observed success rate of 91.6% and 100% (3/3), respectively. Three patients had minor complications (post-procedure pain, fever, and pneumoperitoneum), which were managed conservatively. CONCLUSION: Endoscopic interventions in patients with altered GI anatomy are safe.

EUS-guided Gall Bladder Drainage in Severe Liver Disease: A Single-center Experience in Critically Ill Cirrhotics.

Background and Aims: Acute calculous cholecystitis with impending gall bladder perforation in severe liver diseases including decompensated cirrhosis and acute-on-chronic liver failure (ACLF) is difficult to manage, due to the procedures such as cholecystectomy and per cutaneous cholecystostomy being associated with high risk and complications in these patients. Methods: Four cases of severe liver disease with acute calculous cholecystitis who presented to the Institute of Liver and Biliary Sciences (New Delhi, India) for further management were included in the study if they underwent endoscopic ultrasound-guided gall bladder drainage (EUS-GBD). The patients were followed up for a minimum of 3 months and outcomes were recorded. Results: Four cases of severe liver disease (three ACLF and one decompensated cirrhosis), with model for end-stage liver disease scores of 24, 26, 23 and 25 respectively, presented with acute calculous cholecystitis (Tokyo grade III) and systemic sepsis (high total leukocyte counts). Their international normalized ratios were 2.3, 2.6, 2.2 and 2.9 respectively, and two were in shock, requiring inotropes at presentation. Ultrasonography of the abdomen confirmed hugely distended gall bladder with stone impacted at the neck and moderate ascites. All these cases underwent EUS-GBD by linear echo endoscope, and had the gastric wall punctured in the antrum using a 19G access needle followed by dilatation of the tract using controlled radial expansion balloon and Sohendra dilator. In three cases, the plastic stents were placed. In the fourth case, a Nagi stent was placed. All the patients recovered and were discharged within a week. Conclusions: EUS-GBD is challenging in severe liver disease but represents a life-saving procedure, and hence can be attempted in such critically ill patients with utmost care and precaution.

AKI persistence at 48 h predicts mortality in patients with acute on chronic liver failure.

BACKGROUND AND AIM: Management of acute kidney injury (AKI) in cirrhotics has undergone a paradigm change. We evaluated the impact of AKI persistence at 48 h on outcome in patients with acute on chronic liver failure (ACLF). METHODS: Consecutive patients with ACLF (n = 373) were prospectively followed. AKI was defined as increase in serum creatinine of 0.3 mg/dl or 1.5- to 2-fold from baseline. Persistent AKI was defined as nonresponsive AKI at 48 h with respect to admission serum creatinine. RESULTS: AKI at admission was present in 177 (47.5 %) patients. At 48 h, 73 % patients had persistent AKI and 27 % had responsive AKI. High Model for End-Stage Liver Disease (MELD) (≥26) [p, odds ratio (OR), 95 % confidence interval (CI)] [<0.001, 3.65 (2.1-3.67)], systemic inflammatory response syndrome (SIRS) [0.03, 1.6 (1.02-21.6)], and age (≥42 years) [0.03, 1.84 (1.19-2.85)] were significant predictors of AKI persistence. Persistent AKI was associated with significantly higher in-hospital mortality [p < 0.001, hazard ratio (HR) 1.7, 95 % CI 1.32-2.27]. We further found a lower cutoff for serum creatinine of 1.14 mg/dl at 48 h with better sensitivity of 61 %, specificity of 61 %, and likelihood ratio (LR+) of 1.6, correctly classifying 61 %, as against the conventional cutoff of 1.5 mg/dl with sensitivity of 37 %, specificity of 57 %, and LR+ of 3.3, correctly classifying 56 %. This new cutoff also predicted mortality with higher odds (OR 2.4, 95 % CI 1.3-4.8) as compared with the conventional cutoff (OR 2.1, 95 % CI 1.1-4.1). CONCLUSION: AKI persistence at 48 h predicts mortality better than serum creatinine of 1.5 mg/dl in patients with ACLF. Serum creatinine value of 1.14 mg/dl and smaller increases in its value should be considered for risk stratification of patients with ACLF for interventional strategies.

Pregnancy-related liver disorders.

Pregnancy-related liver disorders accounted for 8% of all maternal deaths at our center from 1999 to 2011. Of the three pregnancy-related liver disorders (acute fatty liver of pregnancy (AFLP), HELLP (Hemolysis, elevated liver enzymes, low platelets) syndrome and pre-eclamptic liver dysfunction, which can lead to adverse maternal and fetal outcome, AFLP is most typically under - diagnosed. Risk of maternal death can be minimised by timely recognition and early/aggressive multi-specialty management of these conditions. Urgent termination of pregnancy remains the cornerstone of therapy for some of these life threatening disorders, but recent advancements in our understanding help us in better overall management of these patients. This review focuses on various aspects of pregnancy-related liver disorders.