Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury.

Background: A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival. Methods: A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included. Predictors of HRS reversal were identified by logistic regression analysis. Survival analysis was performed using the Kaplan-Meier method, and Cox regression models were used to determine independent predictors of mortality. Results: Complete response to therapy was observed in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete treatment response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (ΔRRI) by day 3 of treatment. Independent predictors of HRS reversal were the presence of SIRS at baseline (P=0.022; odds ratio [OR] 15.74, 95% confidence interval [CI] 1.47-167.82) and ΔRRI ≥5% by day 3 of treatment (P=0.048; OR 6.67, 95%CI 1.021-43.62). Mean transplant-free survival at 6 months was significantly better in treatment responders (148 vs. 90 days, P<0.001). Independent predictors of 6-month mortality were response to treatment (P=0.004) and model for end-stage liver disease-sodium >23 (P=0.018). Conclusions: SIRS and ΔRRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation.

A case-cohort study of left ventricular diastolic dysfunction in patients with cirrhosis: the liver-heart axis.

Background: Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival. Methods: A total of 203 cirrhosis patients were enrolled and underwent investigations, including 2-dimensional echocardiography with tissue Doppler imaging, and 139 patients with LVDD (cases) were compared with 64 patients without LVDD (controls). Logistic regression and Kaplan-Meier analysis were applied. Results: Mean age was 52.76±10 years. Among LVDD patients, 56% had grade-1, and 44% had grade-2 LVDD. Cirrhosis related to NASH had a more significant association with LVDD (P<0.001) than other etiologies. LVDD was significantly associated with a greater incidence of Child-Turcotte-Pugh (CTP) class C (P<0.001), higher model for end-stage liver disease scores (P=0.001), duration of cirrhosis >2 years since diagnosis (P=0.028), ascites (P<0.001), hepatic encephalopathy (P<0.010), hepatorenal syndrome (P<0.001), and a history of obesity (P=0.004). Multivariate analysis showed that higher CTP score, ascitic fluid protein and prolonged QTc interval were independently associated with LVDD (P=0.009; P=0.018; P=0.016, respectively). Kaplan-Meier survival analysis showed significantly poorer survival status in patients with higher grades of LVDD (P<0.001). The area under the receiver operating characteristic curve (0.78) was greatest for ascitic fluid protein in predicting LVDD, with a cutoff of >1 g/dL. Conclusions: Higher CTP score, prolonged QTc, higher ascitic fluid protein levels, and poor survival are significantly associated with LVDD. Ascitic fluid protein >1 g/dL could be an indicator for evaluating LVDD.

Comparison of conventional scoring systems versus MAGIC score to predict short-term mortality in patients hospitalized for alcoholic hepatitis.

BACKGROUND: Multiple prognostic models are available to predict mortality in alcoholic hepatitis (AH) which are of modest benefit, but the best model remains unexplored. METHODS: This is a retrospective analysis (2012-2015) of AH patients. Conventional prognostic scoring systems viz. Maddrey's Discriminant Function (mDF), Age Bilirubin International Normalized Ratio and Creatinine (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), and the Model for End-stage Liver Disease score (MELD), were compared with Model for AH to Grade the Severity in an Asian patient cohort (MAGIC) score, using area under the ROC curves for ascertaining 30/90-day mortality. RESULTS: Eighty-eight patients (100% male); mean (SD) age of 45.6 (7.6) years with a follow-up of 80.7 (45.1) days were included. The 30 and 90-day mortality were 21 (23.9%) and 42 (47.7%), respectively; the commonest cause being sepsis in 22 (48.9%) patients. Survival probabilities for mDF < 32 and mDF > 32 were 100% and 42.25% ± 4.46%, respectively (p = .001). The mean (SD) scores of mDF, MELD and GAHS were significantly higher in deceased patients 70.8 (26.5), 23.4 (5.2), 8.1 (1.01), respectively, as compared to those who survived 40.8 (23.1), 18.9 (5.1), 7.3 (0.9), respectively; p = .001. ABIC and MAGIC scores were higher among the deceased, but were not significant. mDF had the best predictive AUROC value 0.872, followed by MELD 0.772, and MAGIC 0.626, respectively. mDF was significantly superior in comparison to MAGIC score (p < .001). CONCLUSION: This study showed that mDF had a better predictive performance than other scoring systems in patients with AH.

Quality of life, caregiver burden and mental health disorders in primary caregivers of patients with Cirrhosis.

BACKGROUND AND AIMS: Caregivers are needed for cirrhotic patients as there is progressive decline in cognition and self-care. We intend to study the quality of life (QOL), psychosocial burden and prevalence of mental health disorders among caregivers. METHODS: Cross-sectional study where caregivers, defined as person who takes responsibility of providing care to patient, of cirrhotic patients were included. Short form 36 health survey (SF-36) to assess QOL, Zarit Burdern Index12 (ZBI) for caregiver burden (CB). Patient Health Questionnaire (PHQ) identified depression and Generalized Anxiety Disorder (GAD-7) questionnaires, anxiety. RESULTS: Of 132 caregivers, mean age of caregiver was 41.2 ± 10.3 years, with female preponderance. Mean MELD was 21.4 ± 7, majority belonged to CHILD C. Comparing the SF36 score of caregivers to normal population showed lower level of QOL for caregivers. Mean ZBI score - 14 ± 5.8. Mean GAD score - 8.1 ± 5.1, 54 (41%) had anxiety. Mean PHQ score - 7.8 ± 5.2, 45 (34%) had depression. REGRESSION ANALYSIS: Alcoholic cirrhosis, history of hepatic encephalopathy (HE), Anxiety, Depression and recidivism predicted CB. Treatment costs (ODDS-1.15), alcoholic cirrhosis (ODDS -8.9), history of HE (ODDS-7.5) and caregiver duration (ODDS-0.25) predicted anxiety. Treatment costs (ODDS-1.5), caregiver age (ODDS-0.87), spouse as caregiver (ODDS-10.9) and higher education (ODDS-0.79) predicted depression. CONCLUSIONS: Caregivers of cirrhotic patients have high prevalence of CB with low QOL and high incidence of anxiety and depression, compared with the general population. Alcoholism in patients precipitates while higher education helps cope up with these disorders.

Imaging of infracolic and pelvic compartment by linear EUS.

The peritoneal cavity is subdivided into supracolic and infracolic compartments by transverse mesocolon, which attaches the colon to the posterior abdominal wall. Infracolic compartment is subdivided into right and left compartment by small bowel mesentery. Left infracolic space freely communicates with pelvic compartment. The infracolic compartment contains the coils of small bowel which is separated from paracolic gutter on either side by ascending and descending colon. Pelvic compartment mainly contains bladder, rectum and genital organ (prostate, seminal vesicle in male and uterus in female). The evaluation of different compartments of peritoneum is gaining importance in multimodality imaging. It has become essential that clinicians and endosonographers thoroughly understand the peritoneal spaces and the ligaments and mesenteries that form their boundaries in order to localize disease to a particular peritoneal/subperitoneal space and formulate a differential diagnosis on the basis of that location. In this article we describe the applied EUS anatomy of peritoneal ligaments, infracolic and pelvic compartments of peritoneum and there technique of imaging from stomach, duodenum, sigmoid colon and rectum. Imaging from stomach images the infracolic compartment through transverse mesocolon, imaging from duodenum images the infracolic compartment through the mesentery and imaging from rectum and sigmoid images the infracolic and pelvic compartments through the sigmoid mesocolon and pelvic peritoneum.

A paradoxical role for an acute phase reactant in decompensated cirrhosis.

BACKGROUND: This study aims to determine the predictive power of baseline C-reactive protein (CRP) value in cirrhotic patients with ascites, without overt infection, that might lead to spontaneous bacterial peritonitis (SBP)/ cellullitis. METHODS: 152 consecutive cirrhotic patients with ascites, without overt infection were included in the study, after measuring the baseline CRP value. All patients were followed up for a duration of one year, or till development of SBP/cellulitis. RESULTS: Baseline CRP was elevated in 76.8% of the patients. Development of infection was observed in 78 (51.3%) patients. SBP was diagnosed in 54 patients, cellulitis was documented in 15 patients. 9 patients had simultaneous SBP and cellulitis Baseline CRP was 10.2 ± 6.34 mg/dL in the group who developed infection, it was 4.81 ± 4.41 mg/dL in the group who did not develop infection (p = 0.002). Baseline CRP > 9.5 mg/dL, serum albumin < 2.8 g/dL and a previous history of infection were independent predictors of developing SBP/cellulitis. CONCLUSIONS: Along with low serum albumin and previous history of infection, CRP can be used as a predictive tool for early detection of infection, thus enabling to reduce the morbidity and mortality.

Non-typhoidal salmonella: an unusual cause of spontaneous bacterial peritonitis in decompensated cirrhosis.

Salmonella typhimurium, a non-typhoidal salmonella, is an unusual cause of spontaneous bacterial peritonitis (SBP). It is usually reported in asymptomatic patients with normal or high ascitic fluid protein levels with underlying immunosuppression, as high opsonic activity in the ascitic fluid of these patients protects them from the usual organisms causing spontaneous bacterial peritonitis, unless they are exposed to a particularly virulent organism like salmonella. We report a case of culture-proven non-typhoidal salmonella in a patient with decompensated cirrhosis, with low protein and without any underlying immunosuppression, and no other source to explain its origin.

Bilirubin, aspartate aminotransferase and platelet count score: a novel score for differentiating patients with chronic hepatitis B with acute flare from acute hepatitis B.

BACKGROUND: Early therapy improves the outcome in patients with chronic hepatitis B with acute flare (CHB-AF). However in mesoendemic countries, it is difficult to differentiate CHBAF from acute hepatitis B (AHB). The aim of this study was to formulate a clinical score to differentiate CHB-AF from AHB in patients presenting with an acute hepatitis-like picture. METHODS: Patients with a protracted clinical course of >2 months with elevated liver enzymes and positive hepatitis B virus DNA, who had undergone liver biopsy were included in this study. The clinical and laboratory profiles were compared between patients with biopsy suggestive of CHB-AF and AHB. RESULTS: Of the 75 patients included, 32 patients had a liver biopsy suggestive of CHB-AF. At 6 months, HBsAg clearance was lower in the CHB-AF group (9.4 vs. 76.7%). Presence of prodrome, platelet count, aspartate aminotransferase (AST), alanine aminotransferase and bilirubin levels and presence of anti-core antibody (IgM anti HBc) were lower in CHB-AF group (P<0.01). Using the receiver operating characteristic curve, peak bilirubin level, peak AST levels and least platelet count within the first 8 weeks had the highest predictive power. Optimal values of platelet <2.4×105/µL, peak bilirubin <4.5 mg/dL and AST <550 IU/L were given a point each. On internal validation a score of 2 had 86% specificity, 70.1% sensitivity and 82.7% diagnostic accuracy in predicting CHB-AF. CONCLUSION: Bilirubin, AST and platelet count (BAP) score may be helpful in differentiating CHB-AF from AHB. A score of >2 could strongly suggest CHB-AF. However the score requires further validation.

Helicobacter pylori infection in patients with liver cirrhosis: prevalence and association with portal hypertensive gastropathy.

BACKGROUND: The role of Helicobacter pylori (H. pylori) in the pathogenesis of portal hypertensive gastropathy (PHG) in cirrhotic patients is poorly defined. The aim of this study was toinvestigate the prevalence of H. pylori infection and its association with PHG in patients with liver cirrhosis. METHODS: Seroprevalence of H. pylori was tested in 70 cirrhotic patients with PHG (cases) and 70 cirrhotic patients without PHG (controls) using an anti-H. pylori IgG ELISA. All patients underwent upper gastrointestinal endoscopy to assess the severity of PHG and grade of varices. RESULTS: The presence of H. pylori was observed in 31 (44.3%) cirrhotic patients with PHG (cases) compared to 19 (27.1%) cirrhotic patients without PHG (controls). The risk estimate showed a significant association between H. pylori and PHG in cirrhotic patients (P=0.034, OR 2.134, 95% CI 1.052-4.327). Out of the 31 patients with PHG and H. pylori infection, 19 had severe PHG and 12 had mild PHG while 5 patients had severe PHG and 34 had mild PHG in the group of H. pylori negative patients. The difference was statistically significant (P<0.001, OR 10.767, 95% CI 3.293-35.205). Of the 70 patients with PHG, 24 had severe PHG and of these 18 (75%) were in Child C compared to 6 (25%) in Child B. CONCLUSION: There is significant association between H. pylori infection and PHG in cirrhotic patients which is also related to severity of PHG. Thus, H. pylori needs to be eradicated in cirrhotic patients with PHG.

QT interval prolongation: a risk factor for development of hepatorenal syndrome in cirrhotic patients with acute variceal bleeding.

BACKGROUND: This study aimed to assess whether QT interval prolongation is an independent risk factor for development of hepatorenal syndrome (HRS) in cirrhotic patients with acute variceal bleeding. METHODS: 78 consecutive cirrhotic patients with acute variceal bleeding were included in the study. All patients were evaluated before bleeding (T0), during bleeding (T1) and 6 weeks later (T2). RESULTS: HRS developed in 14 (17.9%) patients. QT corrected by heart rate (QTc) prolonged at T1, returning towards baseline at T2 (mean ± SD; from 424.0 ± 10.2 to 461.2 ± 17.6 to 426.1 ± 8.8ms, P < 0.001). At T1, patients who developed HRS had longer QTc (P = 0.017) and lower serum sodium (P = 0.039). QTc and serum sodium independently predicted HRS; the best cut-off values were QTc > 468 ms and sodium < 120 mEq/L. Patients on beta-blocker were found to have significant risk for developing HRS (p = 0.040). Based on these three factors, the risk for HRS was nil for patients without risk factors; 6.1%, 11.1%, and 83.3% for those with one, two or three risk factors, respectively (p < 0.001). CONCLUSIONS: Acute variceal bleeding causes further prolongation of QTc in cirrhosis. The combination of beta-blocker, QTc interval and serum sodium can aid in early detection of patients at increased risk of developing bleed-precipitated HRS, thus improving their outcome.

Splenic abscess due to chronic melioidosis in a patient previously misdiagnosed as tuberculosis.

Melioidosis is endemic in Southeast Asia and Northern Australia. Sporadic cases have been reported from many parts of the world where it has an epidemic potential with high-rate fatality cases. In non-endemic areas, melioidosis may be misdiagnosed with common diseases and this may prove fatal. Sporadic cases of melioidosis are mistaken for tuberculosis in India. We report a case of splenic abscess due to chronic melioidosis who was earlier misdiagnosed as tuberculosis and underwent anti-tuberculosis therapy. Following treatment of melioidosis his symptoms subsided. This case is reported because of the rarity of the disease and to highlight the importance of looking for melioidosis in patients with splenic abscess even in non-endemic areas.