UNASSIGNED: Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia.
UNASSIGNED: This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI.
UNASSIGNED: 309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria (P < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days (P < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI.
UNASSIGNED: Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days.
UNASSIGNED: SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.

UNASSIGNED: The NAFLD decompensation risk score (the Iowa Model) was recently developed to identify patients with nonalcoholic fatty liver disease (NAFLD) at highest risk of developing hepatic events using three variables-age, platelet count, and diabetes.
UNASSIGNED: We performed an external validation of the Iowa Model and compared it to existing non-invasive models.
UNASSIGNED: We included 249 patients with NAFLD at Boston Medical Center, Boston, Massachusetts, in the external validation cohort and 949 patients in the combined internal/external validation cohort. The primary outcome was the development of hepatic events (ascites, hepatic encephalopathy, esophageal or gastric varices, or hepatocellular carcinoma). We used Cox proportional hazards to analyze the ability of the Iowa Model to predict hepatic events in the external validation (https://uihc.org/non-alcoholic-fatty-liver-disease-decompensation-risk-score-calculator). We compared the performance of the Iowa Model to the AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and the FIB-4 index in the combined cohort.
UNASSIGNED: The Iowa Model significantly predicted the development of hepatic events with hazard ratio of 2.5 [95% confidence interval (CI) 1.7-3.9, P < 0.001] and area under the receiver operating characteristic curve (AUROC) of 0.87 (CI 0.83-0.91). The AUROC of the Iowa Model (0.88, CI: 0.85-0.92) was comparable to the FIB-4 index (0.87, CI: 0.83-0.91) and higher than NFS (0.66, CI: 0.63-0.69) and APRI (0.76, CI: 0.73-0.79).
UNASSIGNED: In an urban, racially and ethnically diverse population, the Iowa Model performed well to identify NAFLD patients at higher risk for liver-related complications. The model provides the individual probability of developing hepatic events and identifies patients in need of early intervention.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

UNASSIGNED: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India.
UNASSIGNED: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC.
UNASSIGNED: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response.
UNASSIGNED: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

UNASSIGNED: Although extensive experimental evidence on the process of liver regeneration exists, in humans, validation is largely missing. However, liver regeneration is critically affected by underlying liver disease. Within this project, we aimed to systematically assess early transcriptional changes during liver regeneration in humans and further assess how these processes differ in people with dysfunctional liver regeneration.
UNASSIGNED: Blood samples of 154 patients and intraoperative tissue samples of 46 patients undergoing liver resection were collected and classified with regard to dysfunctional postoperative liver regeneration. Of those, a matched cohort of 21 patients were used for RNA sequencing. Samples were assessed for circulating cytokines, gene expression dynamics, intrahepatic neutrophil accumulation, and spatial transcriptomics.
UNASSIGNED: Individuals with dysfunctional liver regeneration demonstrated an aggravated transcriptional inflammatory response with higher intracellular adhesion molecule-1 induction. Increased induction of this critical leukocyte adhesion molecule was associated with increased intrahepatic neutrophil accumulation and activation upon induction of liver regeneration in individuals with dysfunctional liver regeneration. Comparing baseline gene expression profiles in individuals with and without dysfunctional liver regeneration, we found that dual-specificity phosphatase 4 (DUSP4) expression, a known critical regulator of intracellular adhesion molecule-1 expression in endothelial cells, was markedly reduced in patients with dysfunctional liver regeneration. Mimicking clinical risk factors for dysfunctional liver regeneration, we found liver sinusoidal endothelial cells of two liver disease models to have significantly reduced baseline levels of DUSP4.
UNASSIGNED: Exploring the landscape of early transcriptional changes of human liver regeneration, we observed that people with dysfunctional regeneration experience overwhelming intrahepatic inflammation. Subclinical liver disease might account for DUSP4 reduction in liver sinusoidal endothelial cells, which ultimately primes the liver for an aggravated inflammatory response.
UNASSIGNED: Using a unique human biorepository, focused on liver regeneration (LR), we explored the landscape of circulating and tissue-level alterations associated with both functional and dysfunctional LR. In contrast to experimental animal models, people with dysfunctional LR demonstrated an aggravated transcriptional inflammatory response, higher intracellular adhesion molecule-1 (ICAM-1) induction, intrahepatic neutrophil accumulation and activation upon induction of LR. Although inflammatory responses appear rapidly after liver resection, people with dysfunctional LR have exaggerated inflammatory responses that appear to be related to decreased levels of LSEC DUSP4, challenging existing concepts of post-resectional LR.

UNASSIGNED: Epididymo-orchitis (EO) is a disease of both the epididymis and ipsilateral testis. Brucellar epididymo-orchitis (BEO) is an uncommon localized infection of the testis and epididymis which occurs in about 2-14 % of all patients with brucellosis as a result of urine Brucella removal or due to blood-borne septic metastasis.
UNASSIGNED: Between January 2018 and June 2021, 50 patients with fever, chills, swelling, and pain of the testicle (testicles) were referred to our center. Two approaches were used for the treatment of brucellarepididymo-orchitis among these individuals. Intravenous Gentamicin and Doxycycline were used in seven cases, while Rifampicin was added to this combination for the remaining 43 patients. Intravenous Gentamicin was administered for 7 days and the other drugs were used for 45 days. All patients were followed up for six months by monitoring the symptoms and signs of the disease.
UNASSIGNED: None of the patients had been diagnosed with brucellosis before referral to our clinic. 43 patients were successfully treated by. Intravenous Gentamicin, Doxycycline and Rifampicin, whereas seven patients were fully treated using. Intravenous Gentamicin and Doxycycline. The two therapeutic groups were hospitalized for 7.56 ± 3.45 (3-23) and 10.14 ± 1.77 (8-13) days, respectively. Treatment failure, drug side effects, and disease complications were not observed in any of the cases over a 6-month follow-up period.
UNASSIGNED: Physicians should be alert regarding Brucellarepididymo-orchitis (BEO) within the differential diagnosis of nonspecific epididymo-orchitis, especially in regions where the disease is endemic. Delay in diagnosis or inappropriate management of BEO may result in complications.

Objective: Hydroxytyrosol (HT) is a polyphenol with a wide range of biological activities. Excessive drinking can lead to oxidative stress and inflammation in the liver, which usually develop into alcohol liver disease (ALD). At present, there is no specific drug to treat ALD. In this paper, the protection effect of HT on ALD and the underline mechanism were studied.Methods: HepG2 cells were exposed to ethanol in vitro and C57BL/6J mice were fed with a Lieber-DeCarli ethanol liquid diet in vivo.Results: triglyceride (TG) level in serum and the expression of fatty acid synthase (FASN) were reduced significantly by the treatment with HT The acetaldehyde dehydrogenase (ALDH) activity was increased, the serum level of malondialdehyde (MDA) was decreased, catalase (CAT) and glutathione (GSH) were increased, suggesting that HT may reduce its oxidative damage to the body by promoting alcohol metabolism. Furthermore, according to the mRNA levels of tnf-α, il-6 and il-1β, HT inhibited ethanol-induced inflammation significantly. The anti-inflammatory mechanism of HT may be related to suppress the STAT3/iNOS pathway.Dissussion: Our study showed that HT could ameliorate ethanol-induced hepatic steatosis, oxidative stress and inflammation and provide a new candidate for the prevention and treatment of ALD.

UNASSIGNED: Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis.
UNASSIGNED: Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models.
UNASSIGNED: A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis.
UNASSIGNED: An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients.
UNASSIGNED: Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin.
UNASSIGNED: UME-ID-10042.

UNASSIGNED: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb habitually breeds as weed in paddy fields and mostly disseminated in tropical or sub-tropical countries of south and south-east Asia, northern Australia, and west Africa. The plant has been traditionally used to treat fever as a form of poultice. However, no scientific study regarding its toxicity profile has been testified.
UNASSIGNED: The study has been carried out to determine the potential toxicity of the methanol extract from leaves of the Fimbristylis miliacea, employing the technique of acute and subchronic oral administration in mice.
UNASSIGNED: In the acute toxicity study according to OECD guideline 425, oral administration of FM methanol extract at single doses of 2000 and 5000 mg/kg in both sexes of Swiss albino mice was performed. Toxic symptoms, abnormal behavior, changes in body weight, and mortality were observed for 14 consecutive days. In subchronic toxicity study according to OECD guideline 407, plant extract was administered orally at doses of 100, 500, 1000, and 2000 mg/kg daily for 28 days. The general toxic symptoms, abnormal behavior, changes in body weight were observed daily. Biochemical analysis of serum, and histopathological examination of liver were performed at the end of the study.
UNASSIGNED: No mortality, abnormal behavior and urination, changes in sleep, food intake, adverse effect, and non-linearity in body weight have been recorded during acute toxicity study at the doses of 2000 and 5000 mg/kg. Also, in subchronic toxicity study, FM extract produced no mortality or any kind of adverse effects in regards of general behavior, body weight, urination, sleeping routine, and food intake. In case of analysis of thirteen different biochemical parameters, concentrations of aspartate transaminase (AST) and glucose were altered significantly in male and female mice in both acute and subchronic study. Total cholesterol and triglycerides at 5000 mg/kg.bw were changed in male mice in acute toxicity study. On the other hand, female mice had altered triglycerides in subchronic test. All other critical parameters were found unaffected. In subchronic test, histopathological examination of liver demonstrated cellular necrosis at 2000 mg/kg.bw in both male and female mice while minor necrosis was observed at 1000 mg/kg.bw. Thus, the no observed adverse effect level (NOAEL) can be assumed around 1000 mg/kg.bw.
UNASSIGNED: The present study suggests that treatment with FM extract does not reveal significant toxicity.

UNASSIGNED: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD.
UNASSIGNED: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines.
UNASSIGNED: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL.
UNASSIGNED: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk.
UNASSIGNED: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.