The role of gut microbiota in clinical complications, disease severity, and treatment response in severe alcoholic hepatitis.

BACKGROUND: Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH. METHODS: We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events. RESULTS: All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI. CONCLUSIONS: Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.

Transjugular intrahepatic portosystemic shunt (TIPS) placement at index portal hypertensive decompensation (anticipant TIPS) in cirrhosis and the role of early intervention in variceal bleeding and ascites.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement improves survival in patients with refractory/recurrent acute variceal bleeding (RAVB) and refractory ascites/hydrothorax. Recently, early TIPS was shown to reduce rebleeding and improve survival compared to the conventional TIPS. We aimed to study outcomes in patients with cirrhosis undergoing TIPS at first significant portal hypertensive (PHT) decompensation (termed anticipant TIPS) compared to those undergoing TIPS for recurrent or persistent PHT complications (conventional) and compared the former to matched controls on standard medical management (SMT). METHODS: We retrospectively analyzed the clinical, biochemical, and liver disease severity parameters and survival at baseline and post-intervention in cirrhosis patients at two major hepatobiliary intervention centers undergoing anticipant (n = 27) or conventional TIPS (n = 30) and compared the former group to matched historical controls on SMT (n = 35). RESULTS: Baseline parameters were comparable between both the groups, including the Child-Pugh class and model for end-stage liver disease (MELD) scores. Length of stay in the intensive care unit, post-procedure admission rates, and sepsis events were higher among patients undergoing conventional TIPS (p < 0.05). Post-TIPS, at 1 year, overall and sub-grouped survivals were   better in patients undergoing anticipant TIPS. On further sub-group analysis, based on the PHT events and stratified based on Child-Pugh and MELD scores, a higher proportion of patients survived after anticipant TIPS at 1 year. Compared to SMT, patients undergoing anticipant TIPS had significantly lesser hospitalizations, recurrence of varices, and ascites at 1 year, reducing hospital visits and financial burden. CONCLUSIONS: Anticipant TIPS at the first significant PHT event could improve liver-related events and survival compared to   standard medical management and conventional TIPS, respectively.

One disease, many faces-typical and atypical presentations of SARS-CoV-2 infection-related COVID-19 disease.

Since the appearance of the novel coronavirus (severe acute respiratory syndrome-coronavirus-2) and related coronavirus disease 2019 (COVID-19) in China in December 2019, a very high number of small and large patient series have been published in literature from around the world. Even though the classical presentation of COVID-19 is one with respiratory symptoms with or without pneumonia that can be self-limiting or evolve into severe respiratory distress syndrome with multiple organ failure, and secondary bacterial sepsis, a large body of evidence suggests a plethora of other types of clinical presentation. In this exhaustive review, we reviewed all of the published literature on COVID-19 to identify different types of clinical presentations affecting various organ systems, to provide an in-depth analysis that may prove useful for clinicians and health-workers on the frontline, battling the severe pandemic.

Comprehensive review of hepatotoxicity associated with traditional Indian Ayurvedic herbs.

With growing antipathy toward conventional prescription drugs due to the fear of adverse events, the general and patient populations have been increasingly using complementary and alternative medications (CAMs) for managing acute and chronic diseases. The general misconception is that natural herbal-based preparations are devoid of toxicity, and hence short- and long-term use remain justified among people as well as the CAM practitioners who prescribe these medicines. In this regard, Ayurvedic herbal medications have become one of the most utilized in the East, specifically the Indian sub-continent, with increasing use in the West. Recent well-performed observational studies have confirmed the hepatotoxic potential of Ayurvedic drugs. Toxicity stems from direct effects or from indirect effects through herbal metabolites, unknown herb-herb and herb-drug interactions, adulteration of Ayurvedic drugs with other prescription medicines, and contamination due to poor manufacturing practices. In this exhaustive review, we present details on their hepatotoxic potential, discuss the mechanisms, clinical presentation, liver histology and patient outcomes of certain commonly used Ayurvedic herbs which will serve as a knowledge bank for physicians caring for liver disease patients, to support early identification and treatment of those who present with CAM-induced liver injury.

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update.

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding, the transjugular intrahepatic portosystemic shunt (TIPS) procedure continues to remain a focus of intense clinical and biomedical research. By the impressive reduction in portal pressure achieved by this intervention, coupled with its minimally invasive nature, TIPS has gained increasing acceptance in the treatment of complications of portal hypertension. The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy. Moreover, the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions, which was occasionally severe. While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents, hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS. It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS. The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax, portal hypertensive gastropathy, ectopic varices, hepatorenal and hepatopulmonary syndromes, non-tumoral portal vein thrombosis and chylous ascites. It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality. The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.

Beyond the scope and the glue: update on evaluation and management of gastric varices.

Gastric varices are encountered less frequently than esophageal varices. Nonetheless, gastric variceal bleeding is more severe and associated with worse outcomes. Conventionally, gastric varices have been described based on the location and extent and endoscopic treatments offered based on these descriptions. With improved understanding of portal hypertension and the dynamic physiology of collateral circulation, gastric variceal classification has been refined to include inflow and outflow based hemodynamic pathways. These have led to an improvement in the management of gastric variceal disease through newer modalities of treatment such as endoscopic ultrasound-guided glue-coiling combination therapy and the emergence of highly effective endovascular treatments such as shunt and variceal complex embolization with or without transjugular intrahepatic portosystemic shunt (TIPS) placement in patients who are deemed 'difficult' to manage the traditional way. Furthermore, the decisions regarding TIPS and additional endovascular procedures in patients with gastric variceal bleeding have changed after the emergence of 'portal hypertension theories' of proximity, throughput, and recruitment. The hemodynamic classification, grounded on novel theories and its cognizance, can help in identifying patients at baseline, in whom conventional treatment could fail. In this exhaustive review, we discuss the conventional and hemodynamic diagnosis of gastric varices concerning new classifications; explore and illustrate new 'portal hypertension theories' of gastric variceal disease and corresponding management and shed light on current evidence-based treatments through a 'new' algorithmic approach, established on hemodynamic physiology of gastric varices.

Early, late, or no shunt embolization in patients with cirrhosis- and portosystemic shunt-related hepatic encephalopathy.

BACKGROUND: Portosystemic shunts (PSS) are associated with recurrent or persistent hepatic encephalopathy (HE), severe portal hypertensive (PHT) complications, and poor survival in cirrhosis patients. Shunt embolization improves HE in patients with recurrent or persistent HE. The role of early shunt embolization (ESE) in comparison with no and late SE (LSE) in cirrhosis patients with PSS and associated clinical outcomes are not studied. METHODS: ESE was defined as occlusion of PSS in patients with the first episode of spontaneous HE, while LSE was that when performed in patients with recurrent/persistent PSS-related HE. We retrospectively analyzed (November 2016 to March 2019) clinical outcomes, liver disease severity, and survival between patients undergoing ESE (n = 22) vs. LSE (n = 23) and compared ESE with matched historical controls (n = 22) not undergoing shunt embolization, followed-up for 18 months. RESULTS: Males predominated, and the lienorenal type of shunt was the most frequent. Significantly larger and multiple shunts were noted in the LSE group. Arterial ammonia, total bilirubin, and Child-Pugh scores were significantly higher at baseline in the LSE group. Post-procedure length of stay in the intensive unit (mean 0.6 vs. 2.1 days; p = 0.04), infections (31.8% vs. 66.7% beyond 100 days; p = 0.02), recurrence of HE in first 9 months (4.5% vs. 28.6%; p = 0.03), and liver- and PHT-related clinical events beyond 10 months were significantly higher in LSE compared with those in the ESE group respectively. HE beyond 10 months was comparable between both the groups. 18.2% died in ESE while 60.87% died in the LSE group (p = 0.002). Compared with patients on only standard medical care, the occurrence of ascites, variceal bleeding, recurrence of HE, and portal vein thrombosis were significantly lower in those undergoing ESE, even though differences in survival were not significant. CONCLUSIONS: Our study demonstrates the benefits of ESE of large PSS in patients with cirrhosis, probably by improving survival through a reduction in liver and PHT events that warrant validation through prospective randomized controlled multicenter trials.

Update on diagnosis and management of sepsis in cirrhosis: Current advances.

Sepsis and septic shock are catastrophic disease entities that portend high mortality in patients with cirrhosis. In cirrhosis, hemodynamic perturbations, immune dysregulation, and persistent systemic inflammation with altered gut microbiota in the background of portal hypertension enhance the risk of infections and resistance to antimicrobials. Patients with cirrhosis develop recurrent life-threatening infections that progress to multiple organ failure. The definition, pathophysiology, and treatment options for sepsis have been ever evolving. In this exhaustive review, we discuss novel advances in the understanding of sepsis, describe current and future biomarkers and scoring systems for sepsis, and delineate newer modalities and adjuvant therapies for the treatment of sepsis from existing literature to extrapolate the same concerning the management of sepsis in cirrhosis. We also provide insights into the role of gut microbiota in initiation and progression of sepsis and finally, propose a treatment algorithm for management of sepsis in patients with cirrhosis.

Evaluation of Renal Function with Administration of 6% Hydroxyethyl Starch and 4% Gelatin in Major Abdominal Surgeries: A Pilot Study.

BACKGROUND: Synthetic colloids, both starches and gelatins, are commonly used as intravascular fluid replacements on account of increased vascular persistence. The safety on renal outcomes during perioperative use is poorly understood. AIMS: We evaluated renal outcomes of hydroxyethyl starch 6% (HES) and gelatins 4% (G) in patients undergoing elective abdominal surgery. The primary outcome was serum creatinine measurements at baseline, 12 h, 36 h, and 1 week postoperatively (T0, T12, T36, and D7). The secondary outcomes were measurements of prothrombin time (PT), international normalized ratio (INR), fibrinogen, and activated partial thromboplastin time (aPTT) at baseline, 12 h, and 36 h postoperatively. SETTING AND DESIGN: A prospective randomized study was conducted at a tertiary care institute. MATERIALS AND METHODS: Seven-five adult patients received either HES (Group H) or gelatin (Group G) at 20-ml/kg body weight or only crystalloids (Group C) during surgery. Statistical tests used were one-way ANOVA, Student's t-test, Pearson correlation method, and Chi-square test. RESULTS: Serum creatinine assessed at T0, T12, T36, and D7 was comparable between the three groups. PT/INR and aPTT showed no significant increase in values of T12 and T36 in comparison to T0. Fibrinogen level was significantly higher in Group C at T12 and T36. Intraoperative vasopressor use, need for product transfusion, length of intensive care unit stay, and return of bowel function were similar between the three groups. CONCLUSIONS: Intraoperative use of HES (130/0.4) or gelatin (4%) at 20-ml/kg body weight was not associated with renal dysfunction or altered PT and aPTT in adult patients undergoing elective abdominal major surgeries.