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.

Tinospora Cordifolia (Giloy)-Induced Liver Injury During the COVID-19 Pandemic-Multicenter Nationwide Study From India.

Tinospora cordifolia (Giloy) is an herbal supplement commonly used in the Indian alternative medicine system Ayurveda. This herb has been promoted to the public in India as an immune booster to prevent novel coronavirus disease 2019. However, small reports have recently shown an association between Giloy use and the development of herb-induced liver injury (HILI) with autoimmune features in some patients. This large retrospective Indian multicenter study spanning 13 centers at nine locations was designed to identify features and outcomes of HILI temporally associated with Giloy use. Chemical and toxicological analyses of retrieved Giloy samples using state-of-the-art methods were also performed. We report 43 patients, of whom more than half were female, with a median time from initial Giloy consumption to symptom onset of 46 days. Patients presented with acute hepatitis, acute worsening of chronic liver disease (CLD, the most common clinical presentation), or acute liver failure. Causality assessment revealed probable liver injury in 67.4%. The most common autoantibody detected was anti-nuclear antibody. Liver biopsy in a subset revealed HILI associated with autoimmune features and hepatocyte and canalicular cholestasis and neutrophilic and eosinophilic infiltration. Conclusion: Giloy is associated with acute hepatitis with autoimmune features and can unmask autoimmune hepatitis (AIH) in people with silent AIH-related CLD. Further studies on the safety (and efficacy) of untested but heavily promoted herbals in alternative systems of medicine are an unmet need in the interests of public health and are especially important during this global health emergency.

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.

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.

Managing Acute Portal Hypertensive Gastropathy Bleed During the Time of COVID-19 Pandemic: Novelty or Necessity?

Acute bleeding from portal hypertensive gastropathy (PHG) is an extremely rare event in the natural history of cirrhosis. The treatment recommendations include portal pressure reduction strategies including pharmacotherapy with vasoactive agents and beta-blockers and interventional strategies such as transjugular intrahepatic portosystemic shunt placement. In this report, we present the case of a patient with cirrhosis in whom acute PHG-related bleed was managed with endoscopic band ligation, a therapeutic modality which has not been described in current literature. Our decision to re-purpose a technique for variceal bleeding stems from the fact that during the ongoing COVID-19 pandemic, the technical assistance, resource availability, and sourcing of materials that were required for us to follow recommended management guidelines for acute PHG-related bleed was severely affected due to imposed lockdown between districts and states.

Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease.

Gut microbiota has been demonstrated to have a significant impact on the initiation, progression and development of complications associated with multiple liver diseases. Notably, nonalcoholic fatty liver diseases, including nonalcoholic steatohepatitis and cirrhosis, severe alcoholic hepatitis, primary sclerosing cholangitis and hepatic encephalopathy, have strong links to dysbiosis - or a pathobiological change in the microbiota. In this review, we provide clear and concise discussions on the human gut microbiota, methods of identifying gut microbiota and its functionality, liver diseases that are affected by the gut microbiota, including novel associations under research, and provide current evidence on the modulation of gut microbiota and its effects on specific liver disease conditions.

Acute exacerbated severe form of nonalcoholic steatohepatitis leading to acute-on-chronic liver failure: A case series.

We present three patients with uncontrolled metabolic syndrome and acute-on-chronic liver failure in whom, after meticulous evaluation, the acute event was found to be a severe and exacerbated form of nonalcoholic steatohepatitis (NASH), a novel entry in the natural history of non-alcoholic fatty liver disease. This novel disease entity was described partially, 17 years before by Caldwell et al. We discuss current literature, pertinent features, and outcomes associated with a severe form of NASH, which is associated with high mortality.

Outcomes and Toxicology of Herbal Drugs in Alcoholic Hepatitis - A Single Center Experience from India.

Background and Aims: We aimed to study clinical outcomes and liver biopsy features of alcoholic hepatitis (AH) patients on complementary and alternative medicines (CAMs) and to analyze the retrieved drugs for chemical and toxic components linked to drug-induced liver injury. Methods: We retrospectively assessed clinical, biochemical and liver biopsy features of AH patients on CAM with drug-induced liver injury (AH-CAM, n = 27) and compared them to a control group (classical AH, n = 29) on standard of care. Patients without liver biopsy evaluation and other causes for liver disease were excluded. Samples of the CAMs (n = 42) from patients were retrieved and assessed for chemical and toxins. Results: All were males, and significantly worse clinical presentation, biochemical severity, and liver disease scores were notable in patients with AH-CAM. Traditional Ayurvedic-polyherbal formulations were the most commonly used CAM. On liver histology, varying grades of severe-necrosis, severe hepatocellular, canalicular, cholangiolar cholestasis with predominant lymphocytic-portal-inflammation and varying grades of interface-hepatitis were noted in AH-CAM. Analysis of CAMs revealed presence of heavy metals up to 100,000 times above detectable range and adulterants, such as antibiotics, chemotherapy agents, nonsteroidal anti-inflammatory drugs, alcohols, antidepressants, anxiolytics, and recreational drugs. On follow up, a significantly higher number of patients with AH on CAM died at end of 1, 3- and-6-months compared to controls (37% vs. 83%, 29% vs. 62%, 18% vs. 52% respectively; p < 0.001). Conclusions: Patients with AH and CAM-related drug-induced liver injury have extremely poor short-term survival in the absence of liver transplantation compared to those patients with AH on evidence-based management. Early transplant referral and educating on and curbing of CAM use in severe liver disease through strict monitoring of unregulated traditional health practices can help ease the burden of liver-related death.