UNASSIGNED: This study aimed to provide an up-to-date evaluation of the burden of alcohol use disorder and its consequences in Iran from 1990 to 2019.
UNASSIGNED: We assessed the burden of alcohol use disorder and its three subsequent disorders, including cirrhosis and other chronic liver diseases, liver cancer, and cardiomyopathy using Global Burden of Disease (GBD) data. We retrieved data on incidence, prevalence, death, Years of Life Lost from mortality (YLL), Years of healthy life Lost due to Disability (YLD), and Disability-Adjusted Life Year (DALY), which is calculated by summing YLL and YLD values, indices, as well as sociodemographic index (SDI) values.
UNASSIGNED: Age-standardized DALY rate of alcohol use disorder reduced from 55.5 in 1990 to 41.8 per 100,000 in 2019 (-24.1 %). Similarly, age-standardized DALY rates of cirrhosis due to alcohol use (-28.7 %), liver cancer due to alcohol use (-20.9 %), and alcoholic cardiomyopathy (-36.3 %) decreased in Iran from 1990 to 2019. In 2019, alcohol use disorder had the highest DALY rate among individuals younger than 55 years, while cirrhosis due to alcohol use imposed the greatest burden on those older than 55. After adjusting for the year, SDI was negatively associated with the age-standardized DALY rate of liver cancer due to alcohol use (p < 0.001), positively associated with that of alcoholic cardiomyopathy (p = 0.002), and not significantly associated with the burden of other conditions (p > 0.05).
UNASSIGNED: Despite reductions in the age-standardized DALY rate of alcohol use disorders and related consequences among Iranians, they remain a serious public health concern in Iran.

OBJECTIVE: To assess the impact of pre-existing cirrhosis on the outcomes of non-operatively managed blunt liver trauma within the Trauma Quality Improvement Program (TQIP) database.
METHODS: A study of non-operatively managed blunt liver injury patients from 2016 to 2019 was conducted. Propensity score matching analyzed mortality, complications, and hospital length of stay (LOS) for patients with and without cirrhosis. The effect of transcatheter arterial embolization (TAE) was determined using multivariate logistic regression.
RESULTS: Out of 63,946 patients, 767 (1.2%) had pre-existing cirrhosis. Following 1:1 matching, those with cirrhosis experienced more hemorrhage (TAE need: 5.7% vs. 2.7%; transfusion volume: 639.1 vs. 259.3 ml), complications (acute kidney injury: 5.1% vs. 2.8%; sepsis: 2.4% vs. 1.0%), and poorer outcomes (mortality: 19.5% vs. 10.2%; hospital LOS: 11.6 vs. 8.4 days; ICU LOS: 12.1 vs. 7.4 days; ventilator days: 7.6 vs. 1.6). Notably, TAE was associated with increased mortality in cirrhotic patients (odds ratio: 4.093) but did not significantly affect mortality in patients without cirrhosis.
CONCLUSIONS: Within TQIP, pre-existing cirrhosis is a significant negative determinant for outcomes in blunt liver trauma. Cirrhotic patients undergoing TAE for hemostasis face greater mortality risk than non-cirrhotic counterparts.

A consistent feature of chronic liver diseases and the hallmark of pathologic repair is the so-called ductular reaction. This is a histological abnormality characterized by an expansion of dysmorphic cholangiocytes inside and around portal spaces infiltrated by inflammatory, mesenchymal, and vascular cells. The ductular reaction is a highly regulated response based on the reactivation of morphogenetic signaling mechanisms and a complex crosstalk among a multitude of cell types. The nature and mechanism of these exchanges determine the difference between healthy regenerative liver repair and pathological repair. An orchestrated signaling among cell types directs mesenchymal cells to deposit a specific extracellular matrix with distinct physical and biochemical properties defined as portal fibrosis. Progression of fibrosis leads to vast architectural and vascular changes known as liver cirrhosis. The signals regulating the ecology of this microenvironment are just beginning to be addressed. Contrary to the tumor microenvironment, immune modulation inside this \"benign\" microenvironment is scarcely known. One of the reasons is that both the ductular reaction and portal fibrosis have been primarily considered a manifestation of cholestatic liver disease, whereas this phenomenon is also present, albeit with distinctive features, in all chronic human liver diseases. Novel human-derived cellular models and progress in \"omics\" technologies are increasing our knowledge at a fast pace. Most importantly, this knowledge is on the edge of generating new diagnostic and therapeutic advances. Here, we will critically review the latest advances, in terms of mechanisms, pathophysiology, and treatment prospects. In addition, we will delineate future avenues of research including innovative translational opportunities.

BACKGROUND: This cross-sectional study aimed to investigate the impact of metabolic-associated diseases (MADs) on patients with autoimmune hepatitis (AIH).
METHODS: The study analyzed the clinical characteristics of 283 AIH patients who underwent liver biopsy between January 2016 and February 2022 in Ruijin Hospital, Shanghai, China.
RESULTS: Among the identified AIH patients (n = 283), 87.3%, 23.0%, or 43.1% had MADs, non-alcoholic fatty liver disease (NAFLD), or severe fibrosis, respectively. The proportion of diabetes mellitus (DM) was significantly higher in patients with severe liver fibrosis than in those with mild or moderate fibrosis in the AIH cohort (31.1% vs. 18.0%, p < 0.05). Fibrosis was also more severe in patients with NAFLD than in those without (53.8% vs. 39.9%, p < 0.05). Age, Plts, IgG and the presence with MADs were identified as independent predictors of the severity of inflammation in AIH patients. Moreover, severe liver fibrosis (stages 3 to 4) was independently associated with male (OR, 2.855; p = 0.025), γ-GT (OR, 0.997; p = 0.007), and combination with MADs (OR, 4.917; p = 0.006). Furthermore, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients (OR, 2.445, p = 0.038).
CONCLUSIONS: Concurrent MADs, common in AIH patients, is an independent risk factor for severe fibrosis or inflammation; of note, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients. While managing with AIH, routine assessment of co-existing MADs, especially DM, is also important.

UNASSIGNED: The lack of effective non-invasive diagnostic methods for liver fibrosis hinders timely treatment for chronic hepatitis B (CHB) patients, leading to the progression of advanced liver disease. Circulating microRNAs offer a non-invasive approach to fibrosis assessment. MicroRNA-15a/16-1 (miR-15a/16) was reported to be implicated in fibrosis development, but the role of plasma miR-15a/16 in liver fibrosis assessment remains poorly understood. This study explored the importance of plasma miR-15a/16 in assessing liver fibrosis severity of CHB patients.
UNASSIGNED: Quantitative PCR was utilized to measure the levels of plasma miR-15a/16 in 435 patients with CHB and 74 healthy controls. We assessed the correlation between plasma miR-15a/16 levels and liver fibrosis and cirrhosis using Pearson correlation coefficients, multivariate linear and logistic regression models, and smooth curve fitting. Utilizing the receiver operating characteristic (ROC) curve, we examined the diagnostic potential of plasma miR-15a/16 in severe fibrosis and cirrhosis.
UNASSIGNED: Plasma levels of miR-15a/16 in patients with CHB were significantly reduced compared to those in healthy controls. In the CHB cohort, levels were notably decreased in individuals with severe fibrosis or cirrhosis compared to those without severe fibrosis or cirrhosis. Plasma miR-15a/16 levels exhibited a negative relationship with the severity of liver fibrosis, gradually decreasing as the histological fibrosis stage progressed from S0 to S4. Reduced levels of plasma miR-15a/16 were linked to an elevated risk of severe liver fibrosis (miR-15a: odds ratio [OR] = 0.243; 95 % confidence interval [CI]: 0.138, 0.427; miR-16: OR = 0.201; 95 % CI: 0.097, 0.417) and cirrhosis (miR-15a: OR = 0.153; 95 % CI: 0.079, 0.298; miR-16: OR = 0.064; 95 % CI: 0.025, 0.162). MiR-15a achieved an area under the ROC curve of 0.886 and 0.832 for detecting moderate-to-severe fibrosis (S2-S4) and cirrhosis, respectively. MiR-16 demonstrated similar diagnostic values.
UNASSIGNED: Plasma miR-15a/16 levels were negatively correlated with the severity of liver fibrosis in CHB patients and could serve as a new non-invasive indicator in evaluating liver fibrosis.

Spontaneous hemoperitoneum is rare and is often labeled as idiopathic because the source of bleeding is never found. We report the case of a 35-year-old male who died of a splenic vein rupture. The decedent was a chronic alcoholic with a reported history of cirrhosis and medication noncompliance. Internal examination revealed pale visceral organs, marked hemoperitoneum, a fibrotic/nodular liver, esophageal varices, and a ruptured splenic vein. Pertinent microscopic findings include liver parenchyma with bridging fibrous septa, nodules of regenerating hepatocytes, and the presence of Mallory-Denk bodies. The immediate cause of death was determined to be splenic vein rupture with the underlying cause of death being chronic alcoholism. This case is reported to emphasize the importance of correlating past medical history with thorough vascular dissection in cases of spontaneous hemoperitoneum. In a patient with fatal hemoperitoneum and risk factors for splenic vein pathology (ie, cirrhosis, portal vein hypertension), a high suspicion should be kept for splenic vein rupture.

Advanced liver fibrosis can regress following the elimination of causative injuries. Glutamine synthetase (GS) immunohistochemical expression is normally in centrizonal perivenular hepatocytes but can be present in periportal hepatocytes in cases of regressed cirrhosis. This study identified periportal staining and investigated the spectrum of GS staining patterns seen in a range of cirrhotic livers with varying disease processes. The hematoxylin and eosin and GS-stained slides of 88 liver resection/explant specimens with advanced fibrosis cases by different causes were reviewed, and trichrome and orcein stains were used to classify cases as progressive, indeterminate, or regressive. Periportal GS staining was seen in 97% of regressive cases and 84% progressive or indeterminate cases. Liver resection specimens with periportal GS staining showed a variety of patterns, including predominantly perivenular, predominantly periseptal, and perinodular staining. The GS periseptal pattern is more common in regressed cirrhosis compared to progressive cases. The perinodular staining was seen in 16 cases resulting from various etiologies, including biliary atresia, steatotic liver disease, primary biliary cholangitis, and viral hepatitis, 75% of which demonstrated cholestasis. This study further subclassified GS staining patterns of \"periportal\" pattern in cirrhotic liver. Compared to orcein/trichrome staining, GS immunohistochemical staining is not as useful in distinguishing regressed cases from non-regressed cases.

OBJECTIVE: When one considers the significant role of the liver in medication absorption and metabolism, clinicians must appreciate the important ramifications for medication dosing and monitoring in patients with cirrhosis. For many medications, dose adjustments may be necessary to minimize toxicities or avoid adverse effects from drug accumulation. Clinicians could be well served if they can understand in some detail how pharmacokinetic properties are altered in cirrhosis.
METHODS: A PubMed search of the English medical literature starting with 1980 using keywords cirrhosis, pain management, and analgesics was performed, and additional papers were found using references from the first round of papers.
RESULTS: Patients with cirrhosis often have significant reductions in first-pass metabolism, altered volumes of distribution, and marked reductions in both renal and hepatic elimination of drugs. These factors may contribute to much higher levels of drug exposure compared to the general population. In terms of drug dosing, FDA labeling is often ambiguous and even incongruous with observed pharmacokinetic changes.
CONCLUSIONS: This article may provide guidance for clinicians to optimize pain management in people living with cirrhosis.
CONCLUSIONS: Current FDA labeling for dosing analgesic drugs in patients with cirrhosis is either vague or not consistent with findings from newer pharmacokinetic research. With this review, we hope to provide insight and guidance to clinicians on how to dose-adjust medications commonly utilized in pain management in these patients.

BACKGROUND: Current guidelines lack clarity about the optimal duration of octreotide therapy for patients with esophageal variceal hemorrhage (EVH). To address this lack of evidence, we conducted a randomized clinical trial (RCT) of 24-hours versus 72-hours continuous infusion of octreotide for patients with EVH.
METHODS: This multi-center, prospective RCT (NCT03624517), randomized patients with EVH to 24-hour versus 72-hour infusion of octreotide. Patients were required to undergo esophageal variceal band ligation prior to enrollment. The primary endpoint was rebleeding rate at 72 hours. The study was terminated early due to an inability to recruit during and after the COVID-19 epidemic.
RESULTS: For patients randomized to 72-hours (n = 19) of octreotide vs 24-hours (n = 15), there were no differences in the need for transfusion, average pRBC units transfused per patient (3 units vs 2 units), infection (5% vs 0%), mechanical ventilation (11% vs 7%), or the need for vasopressors (5% vs 3%), respectively (none of these differences were statistically significantly different). There were 2 re-bleeding events in the 72-hour group (11%), and no re-bleeding events in the 24-hour group (p = 0.49). 8/15 of patients receiving 24 hours of octreotide were discharged at or before hospital day 3 while none in the 72-hour group was discharged before day 3 (p < 0.001). There was one death (in the 72-hour group) within 30 days.
CONCLUSIONS: A 24-hour infusion is non-inferior to a 72-hour infusion of octreotide for prevention of re-bleeding in patients with EVH. We propose that shortened octreotide duration may help reduce hospital stay and related costs in these patients.

BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis).
METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis.
RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001).
CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.