A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor.

Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late '90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.

A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine.

Complementary and alternative medicine-related liver injuries are increasing globally. Alternative medicine, as an inclusive healthcare practice, is widely accepted in developing and underdeveloped countries. In this context, the traditional systems of medicine in India have been at the forefront, catering to the preventive and therapeutic spectrum in the absence of conclusive evidence for benefits and lack of data on safety. Contrary to popular belief, it is evident that apart from adverse events caused by contamination and adulteration of alternative medicines, certain commonly used herbal components have inherent hepatotoxicity. This narrative review updates our current understanding and increasing publications on the liver toxicity potential of commonly used herbs in traditional Indian systems of medicine (Ayush), such as Tinospora cordifolia (Willd.) Hook.f. & Thomson (Giloy/Guduchi), Withania somnifera (L.) Dunal (Ashwagandha), Curcuma longa L. (Turmeric), and Psoralea corylifolia L. (Bakuchi/Babchi). This review also highlights the importance of the upcoming liver toxicity profiles associated with other traditional herbs used as dietary supplements, such as Centella asiatica (L.) Urb., Garcinia cambogia Desr., Cassia angustifolia Vahl (Indian senna), and Morinda citrofolia L. (Noni fruit). Fortunately, most reported liver injuries due to these herbs are self-limiting, but can lead to progressive liver dysfunction, leading to acute liver failure or acute chronic liver failure with a high mortality rate. This review also aims to provide adequate knowledge regarding herbalism in traditional practices, pertinent for medical doctors to diagnose, treat, and prevent avoidable liver disease burdens within communities, and improve public health and education.

Complementary and alternative medicines and liver disease.

Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.

Citizens protein project: A self-funded, transparent, and concerning report on analysis of popular protein supplements sold in the Indian market.

Protein powders, including those containing herbal and dietary supplements such as vitamins, minerals, and other natural or synthetic ingredients, can be associated with hepatotoxicity. Protein supplements are often mislabeled and deceptive in their contents. In this self-funded transparent study, we extensively analyzed popular protein supplements in India to identify potential hepatotoxic substances based on industrial standards. All products underwent extensive analysis, including total protein content, fungal aflatoxin detection, pesticide residue estimation, heavy metal quantification, steroid detection, and complete organic and inorganic profiling, according to industry standards. Most protein supplements did not meet the labeled and advertised protein content, while certain brands surpassed the stated levels, raising concerns about potential "protein/amino-spiking." In addition, the major brands contained detectable fungal toxins and pesticide residues. Furthermore, many major formulations contained harmful heavy metals such as lead and arsenic, and some featured hepatoxic herbal extracts, particularly green tea extract, turmeric, Garcinia cambogia, and Ashwagandha. Indian-made products were inferior to those manufactured by multinational companies. The presence of various potentially toxic compounds, such as cycloheptatriene, benzene derivatives, toluene, and isopropyl alcohol, within a nonstandardized and unregulated diverse ingredient mix added to the overall concern. We demonstrate that the protein-based herbal and dietary supplement industry requires stringent scrutiny, regulation, and basic safety studies before being marketed. Manufacturers must consider reducing "ingredient complexities" of their protein powders to prevent adverse interactions between herbal and nonherbal components in consumers. Manufacturers must avoid using known toxic ingredients to reduce the avoidable disease burden within the public community.

Development and validation of modified Liaoning score for predicting the prognosis of liver cirrhosis: a retrospective, international multicenter, observational study.

BACKGROUND: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients. METHODS: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China (n = 1944), Jinan, China (n = 485), and São Paulo, Brazil (n = 221). RESULTS: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis (p < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts. CONCLUSIONS: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.

Clinical outcomes related to portal pressures before and after embolization of large portosystemic shunts in cirrhosis.

Objectives: Embolization of large portosystemic shunts effectively controls gastric variceal bleeding and prevents hepatic encephalopathy. The significance of dynamic changes in hepatic venous pressure gradient before and after embolization on clinical events and patient outcomes remains unknown. Methods: In this retrospective single-center series, 46 patients with gastric variceal bleeding, hepatic encephalopathy, or both undergoing embolization (January 2018 to October 2020) were included, and dynamic changes in portal pressures were analyzed against patient outcomes. Results: Males predominated. The most common portosystemic shunt syndrome was the lienorenal shunt. In all, 34 patients underwent embolization for hepatic encephalopathy and 11 for gastric variceal bleeding. The proportion of patients surviving at the end of 12 and 32 months was 86.96 and 54.35%, respectively. The hepatic venous pressure gradient before shunt embolization was 13.4 ± 3.2 and 16.9 ± 3.7 mm Hg after occlusion (p < 0.001). Bleeding from varices on overall follow-up was notable in five patients (10.9%), and overt hepatic encephalopathy in four (N = 42, 9.5%) patients at 6-12 months. The development of infections within 100 days and beyond the first year was associated with the risk of dying at the end of 12 and 32 months, respectively. Elevation of hepatic venous pressure gradient by >4 mm Hg from baseline and an absolute increase to >16 mm Hg immediately post-procedure significantly predicted the development of early- and late-onset ascites, respectively. Conclusion: Close monitoring for the development of infections and optimization of beta-blockers and diuretics after shunt embolization may improve clinical outcomes and help identify patients who will benefit from liver transplantation pending prospective validation.

Association Between Bowel Wall Thickening and Long-Term Outcomes in Decompensated Liver Cirrhosis.

INTRODUCTION: Bowel wall thickening is commonly observed in liver cirrhosis, but few studies have explored its impact on the long-term outcomes of patients with cirrhosis. METHODS: Overall, 118 patients with decompensated cirrhosis were retrospectively enrolled, in whom maximum wall thickness of small bowel, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum could be measured in computed tomography (CT) images. X-tile software was employed to determine the best cut-off values of each segment of bowel wall thickness for predicting the risk of further decompensation and death. Cumulative rates of further decompensation and death were calculated by Nelson-Aalen cumulative risk curve analyses. Predictors of further decompensation and death were evaluated by competing risk analyses. Sub-distribution hazard ratios (sHRs) were calculated. RESULTS: Cumulative rates of further decompensation were significantly higher in patients with wall thickness of ascending colon ≥ 11.7 mm (P = 0.014), transverse colon ≥ 3.2 mm (P = 0.043), descending colon ≥ 9.8 mm (P = 0.035), and rectum ≥ 7.2 mm (P = 0.045), but not those with wall thickness of small bowel ≥ 8.5 mm (P = 0.312) or sigmoid colon ≥ 7.1 mm (P = 0.237). Wall thickness of ascending colon ≥ 11.7 mm (sHR = 1.70, P = 0.030), transverse colon ≥ 3.2 mm (sHR = 2.15, P = 0.038), descending colon ≥ 9.8 mm (sHR = 1.43, P = 0.046), and rectum ≥ 7.2 mm (sHR = 2.38, P = 0.045) were independent predictors of further decompensation, but not wall thickness of small bowel ≥ 8.5 mm (sHR = 1.19, P = 0.490) or sigmoid colon ≥ 7.1 mm (sHR = 0.63, P = 0.076). Small bowel, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum wall thickness were not significantly associated with death. CONCLUSIONS: Colorectal wall thickening, but not small bowel wall, may be considered for the prediction of further decompensation in cirrhosis.

Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.

Use of albumin infusion for cirrhosis-related complications: An international position statement.

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

Timing of endoscopy in patients with cirrhosis and acute variceal bleeding: a single-center retrospective study.

BACKGROUND: The optimal timing of endoscopy in liver cirrhosis with acute variceal bleeding (AVB) remains controversial in current guidelines and studies. METHODS: Consecutive patients with liver cirrhosis and AVB were screened. The timing of endoscopy was calculated from the last presentation of AVB or the admission to endoscopy. Early endoscopy was defined as the interval < 12 h, < 24 h, or < 48 h. A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding and in-hospital mortality were evaluated. RESULTS: Overall, 534 patients were included. When the timing of endoscopy was calculated from the last presentation of AVB, PSM analysis demonstrated that the rate of 5-day failure to control bleeding was significantly higher in early endoscopy group defined as < 48 h (9.7% versus 2.4%, P = 0.009), but not < 12 h (8.7% versus 6.5%, P = 1.000) or < 24 h (13.4% versus 6.2%, P = 0.091), and that the in-hospital mortality was not significantly different between early and delayed endoscopy groups (< 12 h: 6.5% versus 4.3%, P = 1.000; <24 h: 4.1% versus 3.1%, P = 1.000; <48 h: 3.0% versus 2.4%, P = 1.000). When the timing of endoscopy was calculated from the admission, PSM analyses did not demonstrate any significant difference in the rate of 5-day failure to control bleeding (< 12 h: 4.8% versus 12.7%, P = 0.205; <24 h: 5.2% versus 7.7%, P = 0.355; <48 h: 4.5% versus 6.0%, P = 0.501) or in-hospital mortality (< 12 h: 4.8% versus 4.8%, P = 1.000; <24 h: 3.9% versus 2.6%, P = 0.750; <48 h: 2.0% versus 2.5%, P = 1.000) between early and delayed endoscopy groups. CONCLUSION: Our study could not support any significant association of timing of endoscopy with cirrhotic patients with AVB.

Multi-center prospective survey of hepatocellular carcinoma in Kerala: More than 1,200 cases.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered uncommon in India. The aim of this study was to document the demographic characteristics and clinical aspects of HCC in Kerala, India. METHODS: A survey of HCC in Kerala was performed. All gastroenterologists in the region were invited. From May 2018 to April 2020, data was collected in a standardized questionnaire. RESULTS: Forty-three doctors from 15 centers contributed the data. Total 1217 patients were analyzed. This is the largest state-wide survey of HCC in India. HCC was more common in men (90%) than in women (p < 0.01). The etiology of liver disease was hepatitis B virus (7%), hepatitis C virus (4%) and alcohol (40%). Diabetes mellitus was present in 64%, hypercholesterolemia in 17% and hypertension in 38%. Obesity was present in 33% and 15% were overweight. Non-alcoholic fatty liver disease (NAFLD) with or without metabolic syndrome was present in 44%. Serum alpha-fetoprotein was > 400 ng/mL in 24%, total tumor diameter was > 5 cm in 59%, portal vein invasion was seen in 35% and distant metastasis was seen in 15%. Specific therapy was given to 52%. Treatments given included liver transplantation (n = 24), liver resection (n = 39) and transarterial chemoembolization (TACE, n = 184). Although the study was not designed to compare survival, patients who had liver transplantation had longer survival (median 69 months) compared to matched patients given only TACE (median 18 months) (p = 0.03). CONCLUSION: HCC is common in Kerala, India. NAFLD has a predominant association with HCC in Kerala. Most of the patients report late when curative treatment is not possible.

Investigating the correlation between COVID-19 and the progression of chronic liver disease.

INTRODUCTION: The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED: This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION: Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.

Clinical outcomes associated with complementary and alternative medicine-related "immunity-boosting" practices in patients with cirrhosis during the COVID-19 pandemic - an observational study.

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.

A series of homeopathic remedies-related severe drug-induced liver injury from South India.

INTRODUCTION: Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non-liver-related systemic side effects. We present the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center. METHODS: A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy. RESULTS: Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute on chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in 'supposed' ultra-dilute formulations. CONCLUSION: Homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not 'gentle placebos.'

U-shaped relationship between subcutaneous adipose tissue index and mortality in liver cirrhosis.

BACKGROUND: Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence. METHODS: We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson-Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end-stage liver disease score. RESULTS: Majority of patients were male (69.4%) with a mean age of 55.40 ± 10.68 years. SATI had a U-shaped association with mortality (P for non-linearity <0.001). Cutoff values of SATI were 19.7 and 51.8 cm2 /m2 at the points where hazard ratios were just <1.2. SATI was categorized as low (<19.7 cm2 /m2 ), moderate (19.7-51.8 cm2 /m2 ), and high (>51.8 cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P = 0.052) and high versus moderate SATI groups (Gray's test, P = 0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR] = 1.66, 95% confidence interval [CI]: 0.992-2.78, P = 0.054) and was an independent predictor of death (sHR = 1.86, 95% CI: 1.059-3.28, P = 0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR = 1.6, 95% CI: 1-2.54, P = 0.049), and was an independent predictor of death (sHR = 2.007, 95% CI: 1.195-3.37, P = 0.0085). VATI had an irregularly shaped association with mortality (P for non-linearity <0.001). Cutoff values of VATI were 9.8 and 40.2 cm2 /m2 at the points where hazard ratios were just <1.2. VATI was categorized as low (<9.8 cm2 /m2 ), moderate (9.8-40.2 cm2 /m2 ), and high (>40.2 cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P = 0.381) and high versus moderate VATI groups (Gray's test, P = 0.787). Competing risk analyses demonstrated that neither low (sHR = 1.27, 95% CI: 0.599-2.7, P = 0.53) nor high VATI (sHR = 0.848, 95% CI: 0.539-1.34, P = 0.48) was an independent predictor of death compared with moderate VATI. CONCLUSIONS: Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients.

Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection.

Background and Aims: Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock. However, variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis (DC) patients with infection remain unknown. Methods: We conducted 16-srRNA sequencing on stool samples (n=51: sepsis, 27/no sepsis, 24) collected from consecutive DC patients upon admission. Bacterial diversity, significant taxa, and respective metabolic profiling were performed based on subgroup comparisons. Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events. Results: Genera associated with pathogenicity in conditions of immune exhaustion (Corynebacterium, Lautropia) were predominant in patients with sepsis. Metabolic pathways associated with oxidative stress and endotoxemia [lipopolysaccharide (LPS) synthesis and sulfur relay] were significantly upregulated in sepsis. Specific taxa were associated with sites of infection in DC patients. Protective oxidant pathways that increase glutathione were upregulated in those without sepsis. Gammaproteobacteria family of sulfur-metabolizing bacteria, exaggeration of orally predominant pathogens (Prevotella), and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels >1,000 pg/dL. Pathogenic genera related to an immune deficient state was significant in DC with ≥2 infection episodes. Megamonas was associated with survival during the same admission. Conclusions: Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC. Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis, for which larger prospective, well controlled population-based studies remain an unmet need.

Transjugular Intrahepatic Portosystemic Shunt in Chronic Portal Vein Thrombosis-From Routine Recommendations to Demanding Scenarios.

Portal vein thrombosis (PVT), particularly the presence of portal cavernoma, was traditionally considered a relative contraindication for transjugular intrahepatic portosystemic shunting (TIPS) due to the technical difficulties in accessing and maneuvering the portal vein and avoiding the high risk for bleeding periportal collaterals. However, the last decade has seen a surge in the number of studies-mostly case reports and small series of patients-demonstrating that TIPS is not only technically feasible in the vast majority of these patients but also provides effective and long-term control of symptoms associated with portal hypertension in cases refractory to the standard line of therapy. The present article aims to provide a concise but exhaustive overview of the role and the standard and technically difficult TIPS placement scenarios in patients with chronic non-malignant PVT and with and without underlying liver disease. The review is strategically punctuated by exemplary instances from the authors' experience.