Rahul Rai

Gut Microbiota: Its Role in Hepatic Encephalopathy

Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis.

Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy

OBJECTIVES:Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis.METHODS:Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG).RESULTS:Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.CONCLUSIONS:This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE.

Nonalcoholic fatty liver is not associated with incident chronic kidney disease: a large histology-based comparison with healthy individuals.

Background Nonalcoholic steatohepatitis or fibrosis is associated with the increased prevalence of impaired kidney function. It is not known whether nonalcoholic fatty liver (NAFL), which is steatosis without inflammation or fibrosis, is associated with renal impairment as these individuals are not candidates for liver biopsy. Materials and methods The study group included all liver donors who underwent a preoperative liver biopsy for various reasons. NAFL was defined as more than 5% hepatocytes having steatosis and no changes of steatohepatitis and/or fibrosis. Individuals with NAFL were compared with individuals with normal liver histology. Estimated glomerular filtration rate was calculated with the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration methods. Results The mean age of the study group was 35±10.3 years and the mean BMI was 26±3.2 kg/m2. A total of 187 adults having NAFL (80 men) were compared with 186 (88 men) individuals with normal liver histology (controls). Individuals with steatosis had significantly higher BMI (26.8±3.5 vs. 25.5±3.8 kg/m2, P<0.001) and serum alanine transaminase levels (33.8±13.3 vs. 27.2±9.8 IU/l, P<0.000). There was no significant difference in the estimated glomerular filtration rate between the normal histology group and the NAFL group with Modification of Diet in Renal Disease (115±21.8 vs. 114.4±23.2 ml/min, P=0.803) and Chronic Kidney Disease Epidemiology Collaboration methods (113.6±14.8 vs. 113±14.7 ml/min, P=0.668). There was no significant difference as regards serum creatinine (0.73±0.16 vs. 0.74±0.16 mg%, P=0.536), proteinuria (P=0.121), diabetes (1 vs. 4, P=0.372), and hypertension (2 vs. 6, P=0.174) in individuals of both groups. Conclusion Presence of NAFL does not adversely affect renal function.

Liver Transplantation for Alcohol-Related Liver Disease.

Alcoholic liver disease (ALD) is a common indication for liver transplantation. It is a much debated indication for deceased donor liver transplantation due to organ shortage and potential of alcohol relapse after liver transplantation. A six-month abstinence before liver transplantation is required at most centers to decrease chances of alcohol relapse after liver transplantation. However, this rule is not relevant for patients with severe alcoholic hepatitis or severely decompensated patients who are unlikely to survive till 6 months. Long-term care of these patients after liver transplantation includes assessment of relapse, smoking, and surveillance of de novo malignancies. Current review discusses role of abstinence, factors affecting alcohol relapse, liver transplantation for alcoholic hepatitis, role of living donor liver transplantation, and long-term care of ALD patients who undergo liver transplantation.

Yield of endoscopic ultrasound-guided fine needle aspiration for subcentimetric lymph nodes: A comparison to larger nodes

Background and Objectives: Subcentimetric (defined as <1 cm at short axis) lymph nodes are considered benign and there is limited literature on the results of fine needle aspiration (FNA) of these nodes. Methods: Endoscopic ultrasound (EUS) guided FNA was done on 189 lymph nodes in 166 patients with pyrexia of unknown origin (n = 113) or malignancy (n = 53). Subcentimetric lymph nodes (Group A) were compared to nodes with short axis diameter ≥1 cm (Group B). Data are shown as number, percentage, and median (25–75 interquartile range). Results: There was no significant difference between Group A and Group B regarding site of lymph nodes (mediastinal in 73.6 and 72.5%, abdominal in 26.3 vs. 27.4%), number of slides (median 14 vs. 15), needle passes (median 2), and needle used (22 G needle in 85.5% vs. 69.9%). Group A had significantly lesser long axis diameter (1.5 [1.2–2] vs. 2.1 [1.6–2.9] cm) and short axis diameter (0.7 [0.6–0.8) vs. 1.4 [1.1–1.6] cm). A diagnosis (pathologic or reactive) could not be made in 2 (2.6%) and 11 (9.7%) lymph nodes in Group A and Group B, respectively (P = 0.078), due to inadequate material. Respective diagnoses in Group A and Group B were reactive lymphadenopathy (51.3% vs. 18.5%, P = 0.000), granulomatous lymphadenopathy (34.2% vs. 53%, P = 0.011), and malignancy (11.8% vs. 18.5%, P = 0.231). The lymph nodes with granulomatous and malignant change were significantly larger and had higher chances of having sharply demarcated borders as compared to reactive nodes. Conclusion: EUS-guided FNA of subcentimetric lymph nodes have comparable results to larger nodes. Almost half of the subcentimetric lymph nodes are pathologic.