Chathur Acharya

Role of pancreatic fat in the outcomes of pancreatitis.

The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP).The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9-11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis.

The Patient Buddy App Can Potentially Prevent Hepatic Encephalopathy-Related Readmissions

Readmissions are a major burden in cirrhosis. A proportion of readmissions in cirrhosis, especially because of hepatic encephalopathy (HE) could be avoided through patient and caregiver engagement. We aimed to define the feasibility of using the Patient Buddy App and its impact on 30‐day readmissions by engaging and educating cirrhotic inpatients and caregivers in a pilot study.

Chronic Liver Disease in the Human Immunodeficiency Virus Patient

There are an estimated 40 million HIV infected individuals worldwide, with chronic liver disease being the 2nd leading cause of mortality in this population. Elevated liver functions are commonly noted in HIV patients and the etiologies are varied. Viral hepatitis B and C, fatty liver and drug induced liver injury are more common. Treatment options for viral hepatitis C are rapidly evolving and are promising, but treatments are limited for the other conditions and is primarily supportive. Opportunistic infections of the liver are now uncommon. Irrespective of etiology, management requires referral to specialized centers and with due diligence mortality can be reduced.

Gut Microbiota and Complications of Liver Disease

Chronic liver disease, cirrhosis, and its complications are epidemic worldwide. Most complications are mediated through a dysfunctional gut-liver axis. New techniques have made culture-independent analysis of the gut microbiome widespread. With insight into an unfavorable microbiome (dysbiosis) and how it affects liver disease, investigators have discovered new targets to potentially improve outcomes. Dysbiosis is associated with endotoxemia and propagates liver injury due to nonalcoholic steatohepatitis and alcohol. The composition and functionality of the microbiome changes with the development of cirrhosis, decompensation, and with treatments for these conditions. Gut microbiota can be used to predict clinically relevant outcomes in cirrhosis.

Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort

The relative ranking of cirrhosis‐related deaths differs between high‐/middle‐income countries. Gut microbiome is affected in cirrhosis and is related to diet. Our aim was to determine the effect of differing dietary habits on gut microbiota and clinical outcomes. Outpatient compensated/decompensated patients with cirrhosis and controls from Turkey and the United States underwent dietary and stool microbiota analysis. Patients with cirrhosis were followed till 90‐day hospitalizations. Shannon diversity and multivariable determinants (Cox and binary logistic) of microbial diversity and hospitalizations were studied within/between groups. Two hundred ninety‐six subjects (157 U.S.: 48 controls, 59 compensated, 50 decompensated; 139 Turkey: 46 controls, 50 compensated, 43 decompensated) were included. Patients with cirrhosis between cohorts had similar Model for End‐Stage Liver Disease (MELD) scores. American patients with cirrhosis had more men, greater rifaximin/lactulose use, and higher hepatitis C/alcohol etiologies. Coffee intake was higher in Americans whereas tea, fermented milk, and chocolate intake were higher in Turkey. The entire Turkish cohort had a significantly higher microbial diversity than Americans, which did not change between their controls and patients with cirrhosis. In contrast, microbial diversity changed in the U.S.‐based cohort and was the lowest in decompensated patients. Coffee, tea, vegetable, chocolate, and fermented milk intake predicted a higher diversity whereas MELD score, lactulose use, and carbonated beverage use predicted a lower microbial diversity. The Turkish cohort had a lower risk of 90‐day hospitalizations. On Cox and binary logistic regression, microbial diversity was protective against 90‐day hospitalizations, along with coffee/tea, vegetable, and cereal intake. Conclusion: In this study of patients with cirrhosis and healthy controls from the United States and Turkey, a diet rich in fermented milk, vegetables, cereals, coffee, and tea is associated with a higher microbial diversity. Microbial diversity was associated with an independently lower risk of 90‐day hospitalizations. (Hepatology 2018;68:234‐247).

Patient Acceptance of Lactulose Varies Between Indian and American Cohorts: Implications for Comparing and Designing Global Hepatic Encephalopathy Trials

BackgroundnLactulose is the first-line drug for hepatic encephalopathy (HE), but its acceptance widely differs between Western and Eastern studies. Patient preference for lactulose between different parts of the world has not been examined systematically.nnnAimnTo define the preferences and reasons behind acceptance of lactulose in patients from USA and India.nnnMethodsnA discrete-choice questionnaire with six hypothetical scenarios was constructed. Situations 1-3 studied preference for lactulose vs no-lactulose, while 4-6 studied preference for high-dose vs low-dose lactulose varying the overt HE prevention at 6 months and adverse event rates in each situation. This was administered to outpatient cirrhotics without prior/current experience with lactulose after dedicated education.nnnResultsn100 patients (50 Indian, 50 USA) with similar MELD scores were included. A significantly higher proportion of Indian respondents agreed to lactulose in all situations compared to Americans. While their acceptance of lactulose decreased in the situation with the least difference in overt HE prevention, it was consistently higher than Americans. In the high-dose vs low-dose scenario, the relative proportion of American respondents accepting high-dose increased with the higher presented protection against overt HE. On the other hand, Indian respondents remained largely consistent with low-dose lactulose option.nnnConclusionsnThere are significant variations in the acceptance of lactulose in Indian and American populations. The acceptance increases with a more favorable perceived benefit/risk profile, which is strongly influenced by socio-cultural factors. These results have important implications when designing, comparing and interpreting HE trials from different parts of the world.

No Association Between Quick Sequential Organ Failure Assessment and Outcomes of Patients With Cirrhosis and Infections

No Association Between Quick Sequential Organ Failure Assessment and Outcomes of Patients With Cirrhosis and Infections Kavish R. Patidar,* Jawaid Shaw, Chathur Acharya, Leroy R. Thacker,k,¶ Melanie B. White,* Dinesh Ganapathy,* Andrew Fagan, Edith A. Gavis, and Jasmohan S. Bajaj* *Division of Gastroenterology, Hepatology and Nutrition, Division of General Internal Medicine, kDepartment of Biostatistics and Family and Community Health Nursing, Virginia Commonwealth University, Richmond, Virginia; Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, Virginia

Covert and Overt Hepatic Encephalopathy: Current Options for Diagnosis and Treatment

Overt hepatic encephalopathy (OHE) and covert hepatic encephalopathy (CHE) are two clinically distinct entities that are at the end of the spectrum of cognitive impairment due to portal hypertension. They are fraught with diagnostic and treatment challenges, but both could result in serious complications if not intervened upon in a timely fashion. CHE has been recognized as a harbinger to OHE providing an opportunity to intervene. There are numerous diagnostic strategies for CHE, and most require specialized equipment, trained personnel, and time. Diagnosis of OHE is significantly easier compared to CHE. As such, the psychometric tests have been more favored due to less dependence on specialized equipment and personnel, and their ability to be equally reliable compared to neuropsychological tests. While we have learned more about the pathophysiology of hepatic encephalopathy, our treatment modalities have not evolved as much. A collaborative approach to management, with development of easier reliable tests, will help us combat this epidemic.

Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis

OBJECTIVES: Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter‐linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. METHODS: Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90‐days post‐discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross‐sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral‐origin taxa analysis vis‐à‐vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral‐origin taxa was performed pre/post‐intervention. RESULTS: Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90‐day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross‐sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral‐origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral‐origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral‐origin taxa compared to baseline. CONCLUSIONS: PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.

Current Management of Hepatic Encephalopathy

&NA; Hepatic encephalopathy is a state of brain dysfunction resulting from decompensation of cirrhosis. The mortality and morbidity associated with the overt form of hepatic encephalopathy are high, and even the covert form associates with poor outcomes and poor quality of life. We know that the dysfunction is not just an acute insult to the brain but rather results in long‐standing cognitive issues that get worse with each episode of HE. Hence, there is an urgency to accurately diagnose these conditions, start appropriate therapy, and to maintain remission. Currently, we have two mainstay pharmacological treatment options (lactulose and rifaximin), but the narrative is evolving with new therapies under trial. Microbiome manipulation resulting in a favorable change to the gut microbiota seems to be a promising new area of therapy.