Motorized Power Spiral Enteroscopy (MSE): Is Routine Bougienage of the Upper Esophageal Sphincter (UES) Necessary?

Introduction Wire-guided bougienage of the upper esophageal sphincter (UES) was performed routinely before per-oral motorized power spiral enteroscopy (MSE). In the present study, we aimed to answer the clinical question of whether routine bougienage of UES is required. Methods This was a retrospective study that included 20 patients who underwent antegrade spiral enteroscopy for various indications. The feasibility and safety of anterograde MSE without prior bougie dilatation of the upper esophageal sphincter were assessed. The technical success rate (TSR), diagnostic yield, and adverse events (AEs) were also assessed. Results In 16 out of the 20 patients, a spiral enteroscope was taken directly across UES into the esophagus without a prior bougie dilatation. The spiral enteroscope could not be negotiated across UES only in one patient, and bougie dilatation was done. The technical success rate was 100%. The diagnostic yield was 80%. Four patients reported AEs. Conclusions MSE had a good technical success rate and diagnostic yield. Routine dilatation of the UES before the procedure may be unnecessary.

Validity and Reliability of the European Organization Research and Treatment of Cancer Quality of Life Questionnaire-Oesophagogastric 25 in Indian Patients With Corrosive-Induced Benign Refractory Esophageal Strictures.

Background The European organization Research and Treatment of Cancer Quality of Life Questionnaire-Oesophagogastric 25 (EORTC QLQ-OG 25) is designed for patients with esophagogastric cancer. Its performance has never been tested with benign disorders. A health-related quality-of-life questionnaire does not exist for patients with benign corrosive-induced esophageal strictures. Hence, we evaluated the EORTC QLQ-OG 25 in Indian patients with corrosive strictures. Methods The English or Hindi version of QLQ-OG 25 was administered to 31 adult patients undergoing outpatient esophageal dilation at GB Pant hospital, New Delhi. These patients had refractory or recurrent esophageal strictures due to corrosive ingestion and had not undergone reconstructive surgery. Score distribution was analyzed, and item performance was determined based on floor and ceiling effects. Convergent validity, discriminant validity, and internal consistency were checked. Results The average time to finish the questionnaire was 6.70 minutes. Most scales fulfilled convergent validity (corrected item-total correlation >0.4), barring the Odynophagia scale and one item of the Dysphagia scale. Most scales exhibited divergent validity except for odynophagia and one item of dysphagia. Cronbach's alpha was >0.70 for all scales except odynophagia. Responses to questions evaluating taste, cough, swallowing saliva, and talking were highly skewed and had prominent floor effects. Overall, the questionnaire demonstrated good internal consistency, convergent validity, and divergent validity in benign corrosive-induced refractory esophageal strictures patients. Conclusion The EORTC QLQ-OG 25 can be satisfactorily used in patients with benign esophageal strictures to assess health-related quality of life.

Comparing Myelosuppression Frequency in Indian Inflammatory Bowel Disease Patients: A Randomized Trial of Full Dose Versus Gradual Escalation of Thiopurines.

INTRODUCTION: We aimed to compare the frequency of myelosuppression in patients initiating azathioprine (AZA) at full dose versus those undergoing gradual dose escalation. METHODS: Forty patients with inflammatory bowel disease were recruited over one year and randomized into two groups of 20. Group A initiated AZA at a full dose of 2 mg/kg, while group B started at 1 mg/kg with subsequent dose increases at regular intervals. RESULTS: Seventeen patients from each group were included in the final analysis. During follow-up, two patients (11.8%) from group A and four patients (23.5%) from group B experienced relapses (p=0.65). Myelosuppression occurred in two patients (11.8%) from each group. Absolute neutrophil counts in group A tended to have lower median values than those in group B, particularly four weeks after AZA initiation. Univariate analysis identified serum proteins, albumin, and bilirubin as significantly associated with leukopenia, but these factors were not significant according to multivariate analysis. CONCLUSIONS: The incidence of myelosuppression was similar between the groups. Patients with full-dose initiation of AZA had numerically fewer relapses during the follow-up period.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Duodenal strongyloidiasis - Our 15-year histopathological experience at a tertiary gastrointestinal centre.

In order to emphasise the importance of histopathology in the clinically unsuspected diagnosis of duodenal strongyloidiasis, we report six cases diagnosed on duodenal biopsies identified from the database over a period of 15 years, and clinical, endoscopic and histopathological findings were analysed retrospectively. Four were elderly males and the remainder young females. Only one patient had an underlying immunocompromised state. Three presented with cholestatic jaundice and simulated hepatobiliary malignancy. In all cases, endoscopy provided non-specific findings. Only one case showed a predominant eosinophilic infiltrate. Eggs, larvae and adult forms of strongyloides were seen in crypts and showed intense basophilic staining on HE stain. It is concluded that since mostly undetected clinically, duodenal biopsy serves as the first step in the diagnosis of strongyloidiasis. Hepatobiliary manifestations, though very infrequent, should raise the suspicion for strongyloidiasis and thus necessitate the need for duodenal biopsy.

Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus.

Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.

Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis.

BACKGROUND & AIMS: In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites. METHODS: We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders. We included studies in which data on ascites at baseline and on other relevant outcomes during follow-up evaluation were available. We performed separate meta-analyses for patients with vs without ascites. RESULTS: Of the 1113 patients included in the studies, 968 patients (87%) had been treated with nonselective ß-blockers. In 993 patients (89%), HVPG response was defined as a decrease of more than 20% from baseline (>10% in 11% of patients) or to less than 12 mm Hg. In the 661 patients without ascites, responders (n = 329; 50%) had significantly lower odds of events (ascites, VH, or encephalopathy) than nonresponders (odds ratio [OR], 0.35; 95% CI, 0.22-0.56). Odds of death or liver transplantation were also significantly lower among responders than nonresponders (OR, 0.50, 95% CI, 0.32-0.78). In the 452 patients with ascites, responders (n = 188; 42%) had significantly lower odds of events (VH, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome) than nonresponders (OR, 0.27; 95% CI, 0.16-0.43). Overall, odds of death or liver transplantation were lower among responders (OR, 0.47; 95% CI, 0.29-0.75). No heterogeneity was observed among studies. CONCLUSIONS: In a meta-analysis of clinical trials, we found that patients with cirrhosis with and without ascites who respond to treatment with nonselective ß-blockers (based on reductions in HVPG) have a reduced risk of events, death, or liver transplantation.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Incidentally detected asymptomatic hepatitis C virus infection with significant fibrosis: Possible impacts on management.

BACKGROUND AND AIMS: Liver biopsy may be considered in patients with hepatitis C virus (HCV) infection to assess the severity of liver injury and stage of fibrosis, thereby guiding therapeutic decisions. In addition, advanced stage also necessitates surveillance for hepatocellular carcinoma. The aim of this study was to assess whether transaminase (alanine transaminase [ALT]) levels and RNA titers correlate with the histological activity index (HAI) and fibrosis (F) stage in asymptomatic patients with incidentally detected HCV (IDHCV). PATIENTS AND METHODS: Retrospective evaluation of liver biopsies was done in 113 patients with IDHCV, diagnosed during routine screening. Decision of liver biopsy was made on the basis of age, genotype, acceptable clinical, hematological, and biochemical profiles, and willingness of the patients to undergo treatment. Serum ALT levels, HCV RNA titers, and genotypes were correlated with HAI and F stage. RESULTS: Genotyping was done in 77 of the 113 patients, of which genotype 3 was seen in 43 and genotype 1 in 25 patients. A higher fibrosis stage (Ishak's >F2) was noted in 23.8% of the biopsies. Serum ALT showed a significant correlation with the HAI score on liver biopsy (P = 0.01) but not with the stage of fibrosis (P = 0.52). HCV RNA titers did not reveal any correlation with HAI score or fibrosis stage. CONCLUSION: Serum transaminases and HCV RNA titers are poor predictors of disease severity and fibrosis. Since HCV shows a slow disease progression, higher stage may predict a worse prognosis irrespective of the low viral RNA load. Liver biopsy may help guide therapeutic decisions in IDHCV infection.

Secondary prophylaxis of hepatic encephalopathy in cirrhosis of liver: a double-blind randomized controlled trial of L-ornithine L-aspartate versus placebo.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is associated with a poor prognosis. There is no study on the prevention of recurrence of encephalopathy with L-ornithine L-aspartate (LOLA). PATIENTS AND METHODS: We conducted a double-blind randomized controlled trial at a tertiary center. Consecutive patients with cirrhosis who had recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer-based randomization for 6 months. Patients were assessed by psychometric HE scores using five paper-pencil tests, critical flicker frequency test, arterial ammonia, and sickness impact profile scores at inclusion. Primary end point was development of overt HE. RESULTS: Of 306 patients, 150 patients were enrolled. HE recurred in nine (12.3%) of 73 and in 20 (27.7%) of 72 patients receiving LOLA and placebo, respectively (P=0.02), with hazard ratio of 0.389 (95% confidence interval=0.174-0.870). Mortality was similar in both groups (6.8 vs. 13.8%, P=0.18). At 6 months follow-up, there was a significant change in the psychometric hepatic encephalopathy score (2.53±2.18 vs. -0.01±1.92, P<0.001), ammonia level (-23.58±14.8 vs. 1.41±13.34 µmol/l, P<0.001), CFF (5.85±4.82 vs. 0.58±4.53, P<0.001), and SIP scores (-7.89±5.52 vs. -0.95±4.25, P<0.001) in patients treated with LOLA compared with placebo. On multivariate analysis, only MELD score predicted the recurrence of overt HE, with odds ratio of 2.21 (95% confidence interval: 1.526-3.204, P<0.001). CONCLUSION: LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in psychometric hepatic encephalopathy score, ammonia level, critical flicker frequency scores, and health-related quality of life.

Gastric Varices in Cirrhosis vs. Extrahepatic Portal Venous Obstruction and Response to Endoscopic N-butyl-2-cyanoacrylate Injection.

BACKGROUND: Gastric varices (GV) are found in patients with portal hypertension. Incidence of bleeding from GV is relatively low, but is severe, and associated with higher mortality. AIMS AND OBJECTIVES: To compare the types of GV in cirrhosis vs. extrahepatic portal venous obstruction (EHPVO) and the results of endoscopic N-butyl-2-cyanoacrylate (NBC, glue) injection. METHODS: Four hundred and fifty-four patients undergone glue injection of GV for primary prophylaxis or control of bleeding for first episode of bleeding from GV between August 2010 and August 2015 were analyzed. RESULTS: Of 454 patients, 64% (n = 292) were cirrhotics and 36% (n = 162) had EHPVO. Types of GV were GOV1 in 16.4% (n = 48) of cirrhotics vs. 7.4% (n = 12) of EHPVO, GOV2 in 76.7% (n = 224) of cirrhotics vs. 53.1% (n = 86) of EHPVO, Isolated gastric Varices (IGV1) in 39.5% (n = 64) of patients with EHPVO vs. 6.8% (n = 20) cirrhotics. The patients were treated with NBC injections. The mean volume of glue injected was 2.89 ± 1.59 ml over a median of 1 session (range: 1-7). The total volume of glue required was lower in cirrhotics (2.44 ± 1.17 ml vs. 3.69 ± 1.91 ml, P < 0.05) than in EHPVO patients. One hundred and seventeen (40.1%) of cirrhotics required >1 sessions of glue injection as compared to 102 (63%) of EHPVO patients. Over mean follow up of 14.7 ± 6.46 months, rebleeding (10% vs. 13%) was similar in patients with cirrhosis and EHPVO and mortality (15.4% vs. 2.5%) was higher in cirrhotics than EHPVO. CONCLUSION: In patients with bleeding from GV, GOV2 are more common in cirrhotics and IGV1 in patients with EHPVO. Patients with EHPVO required higher total volume of glue and more glue sessions for GV obturation.

Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study.

BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis. METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death. RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P < 0.001). CONCLUSION: Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF.

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.

Management of overt hepatic encephalopathy.

Hepatic encephalopathy (HE) is an important complication of cirrhosis with significant morbidity and mortality. Management of HE primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as non-absorbable disaccharides, antimicrobial agents like rifaximin and l-ornithine l-aspartate. The non-absorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and in primary and secondary prophylaxis of HE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Rifaximin is effective in treatment of HE and recent systemic reviews found it comparable to disaccharides and is effective in secondary prophylaxis of HE. Many agents like l-ornithine l-aspartate, probiotics, zinc, sodium benzoate have been tried either alone or in combination with lactulose for the treatment of HE. Combination therapy of disaccharides either with rifaximin, l-ornithine l-aspartate, probiotics for the treatment of HE needs further validation in large studies.

Features of hepatitis C virus infection, current therapies and ongoing clinical trials in ten Asian Pacific countries.

Estimated hepatitis C virus (HCV) infection rates in the general populations were 1.3, 0.9, 0.4-1.0, 14.7, 0.1-0.3, 0.9-1.9, 1.0-2.0, 5, 4.4-8.6 and 0.5-1.3 % in Australia, Bangladesh, Mainland China, Egypt, Hong Kong, India, Japan, Pakistan, Taiwan and Turkey, respectively. The main HCV genotypes (Gs) are G1, G3, G1b, G4, G1b, G3, G1b, G3, G1b and G2, and G1 in Australia, Bangladesh, Mainland China, Egypt, Hong Kong, India, Japan, Pakistan, Taiwan and Turkey, respectively. Of IL28B genotypes, favorable alleles are ~50 % in Australia and Turkey, but 60-70 % in most of the other Asian countries. Peginterferon plus ribavirin is available in all ten Asian Pasific countries. In addition, HCV NS3/4A protease inhibitors with peginterferon plus ribavirin are currently available in several countries. Clinical trials of interferon-free regimens for HCV are ongoing in most of the ten Asian Pacific countries.

A survey of patterns of practice and perception of minimal hepatic encephalopathy: a nationwide survey in India.

BACKGROUND/AIM: Minimal hepatic encephalopathy (MHE) leads to overt hepatic encephalopathy (HE) and impairs quality of life in patients with cirrhosis. Awareness of MHE and its management among physicians is not known. PATIENTS AND METHODS: We conducted a survey among 673 physicians in India from academic and nonacademic institutes to understand the clinical burden, perceived severity, management patterns, and the barriers to providing care for this condition. RESULTS: Overall awareness of MHE in this survey was 75% (n = 504). Awareness of MHE was significantly higher in physicians working in teaching hospitals compared with those in nonteaching hospitals (79% vs 71%, P = 0.02). Similarly, gastroenterologists were more aware of MHE compared with nongastroenterologists (91% vs 66%, P = 0.001). Only 6.3% physicians screened all of their patients for MHE, whereas frequency of testing for MHE, either being nil or less than 10% of their patients was 64.7%. The most common test was paper and pencil test (86%) and the reason for nonscreening was nonavailability of time to test and also equipment or method (81%). A majority of physicians (88%) think that MHE affects quality of life. Physicians (61%) had an opinion that there should be some registry of MHE regardless of the cost and effort involved. Lactulose was used in 93% of cases, followed by rifaximin (82%) in the management of MHE. CONCLUSION: The overall awareness of MHE was 75% and it was significantly more in physicians of academic institutes. Despite awareness of its effect on quality of life, a majority of physicians did not test for MHE in their day-to-day practice.

Altered frequencies of dendritic cells and IFN-gamma-secreting T cells with granulocyte colony-stimulating factor (G-CSF) therapy in acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a serious hepatic ailment with impaired immunity and poor treatment options resulting high mortality. Treatment with granulocyte colony-stimulating factor(G-CSF) mobilizes CD34(+) cells in ACLF patients; however its effect on impaired immune responses remains to be elucidated. To analyse the effect of G-CSF in immune modulation in ACLF. METHODS: We have analysed the frequencies of circulating and intrahepatic myeloid (mDCs) and plasmacytoid(pDCs) dendritic cells (DCs) and T cells in ACLF patients treated with G-CSF (Group A; n = 23) and placebo (Group B; n = 24) using flow cytometry. IFN-c production was compared in both groups following stimulation of PBMCs with phorbol myristate acetate (PMA). RESULTS: In Group A, circulating and intrahepatic mDCs, pDCs (P < 0.04, P < 0.02) and T cells(CD3, CD4 and CD8) increased significantly post-G-CSF treatment in comparison to placebo group. Importantly in Group A, IFN-c-producing CD8 T cells were significantly decreased (P > 0.05) along with decreased serum bilirubin and international normalized ratio (INR). Intrahepatic DCs and IFN-clevel were compared in survivor and non-survivor. Non-survivors from both groups, showed decreased DCs, high IFN-c level and no improvement in clinical parameters including s-bilirubin and INR. CONCLUSIONS: G-CSF therapy increased the frequencies of dendritic cells and reduced IFN-c secreting CD8 T cells with improved clinical severity indices. Decreased IFN- c production may contribute to reduced hepatocellular damage in ACLF patients.Our observations support the basis for further use of G-CSF therapy as immune modulator in these patients.

Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial.

BACKGROUND: Probiotics, by altering gut flora, may favourably alter portal haemodynamics in patients with cirrhosis. AIM: To investigate the effect of probiotics on portal pressure in patients with cirrhosis. METHODS: Randomized double-blind placebo-controlled trial conducted in G.B. Pant Hospital, New Delhi. A total of 94 cirrhotic patients having large oesophageal varices without history of variceal bleeding were randomized to three treatment groups and given 2 months' treatment with propranolol plus placebo, propranolol plus antibiotics (norfloxacin 400 mg BD) or propranolol plus probiotic (VSL#3, 900 billion/day) randomly assigned in 1:1:1 ratio. Outcome measures were change in Hepatic venous pressure gradient (HVPG): Response rate (Percentage of patients having a decrease from baseline of ≥20% or to ≤12 mm Hg) and changes from baseline; biochemical markers of inflammation: changes from baseline. RESULTS: Adjunctive probiotics increased the response rate compared with propranolol alone (58% vs. 31%, P = 0.046), similar to adjunctive antibiotics (54%). The mean fall in HVPG was greater with either adjunctive probiotics (3.7 mm Hg vs. 2.1 mm Hg, P = 0.061) or adjunctive antibiotics (3.4 mm Hg) than with propranolol alone. Both adjunctive therapies were associated with greater decreases in TNF-α levels (in both peripheral and hepatic venous blood) that resulted from propranolol-only treatment. No clinically relevant between-group differences were observed in the type or frequency of adverse events. CONCLUSIONS: Adjunctive probiotic (VSL#3) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis. Adjunctive probiotic therapy merits further study for reduction in portal pressure.

Gastric Varices in Cirrhosis versus Extrahepatic Portal Venous Obstruction and Response to Endoscopic N-Butyl-2-cyanoacrylate Injection.

BACKGROUND: Gastric varices are found in patients with portal hypertension. Incidence of bleeding from gastric varices is relatively low, but tends to be more severe, and is associated with higher mortality than esophageal variceal bleeding. AIMS AND OBJECTIVES: To compare the prevalence and types of gastric varices in cirrhosis versus extrahepatic portal venous obstruction (EHPVO) and the results of endoscopic N-butyl-2-cyanoacrylate (NBC, glue) injection. METHODS: Eighty six patients presenting with bleeding from gastric varices between August 2010 and August 2011 were retrospectively analyzed. RESULTS: Of 86 patients, 65% (n = 56) were cirrhotics and 35% (n = 30) had EHPVO. Distribution of types of gastric varices showed GOV1 in 14% (n = 8) of cirrhotics vs. 7% (n = 2) of EHPVO, GOV2 in 80% (n = 45) of cirrhotics vs. 53% (n = 16) of EHPVO, IGV1 in 40% (n = 12) of patients with EHPVO vs. 4% (n = 2) cirrhotics. The patients were treated with NBC injections. The mean volume of glue injected was 3.7 ± 2.58 ml over a median of 1 session (range: 1-8). The total volume of glue required was lower in cirrhotics (3.2 ± 2 ml vs. 4.7 ± 3.1 ml, p < 0.05) than in EHPVO patients. Twenty (36%) of cirrhotics required >1 sessions of glue injection as compared to 17 (57%) of EHPVO patients. Over mean follow up of 12 months, rebleeding (9% vs. 10%) and mortality (11% vs. 3%) were similar in patients with cirrhosis and EHPVO. CONCLUSIONS: In patients with bleeding from gastric varices, GOV2 is more common in cirrhotics and IGV1 in patients with EHPVO. Patients with EHPVO required higher total volume of glue and more glue sessions for gastric varix obturation.