Advanced Cirrhosis Research Articles

New perspectives in hepatocellular carcinoma surveillance after hepatitis C virus eradication.

Achieving a sustained virologic response (SVR) through direct-acting antivirals for hepatitis C virus (HCV) infection significantly reduces the long-term risk of hepatocellular carcinoma (HCC), particularly in patients with advanced fibrosis (F3) or cirrhosis (F4). However, despite this improvement, the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate. This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively, especially at advanced fibrosis (F3), and the unclear cost-effectiveness, modality, frequency, and duration of HCC surveillance in individuals with SVR but without cirrhosis. These factors contribute to significant variations in surveillance guidelines recommended by different professional societies. Therefore, there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians. This review article evaluates the existing data, addresses ongoing controversies, and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.

Utilization of aquapheresis among hospitalized patients with end-stage liver disease: A case series and literature review.

Third-spacing of fluid is a common complication in hospitalized patients with decompensated cirrhosis. In addition to ascites, patients with advanced cirrhosis may develop significant peripheral edema, which may limit mobility and exacerbate debility and muscle wasting. Concomitant kidney failure and cardiac dysfunction may lead to worsening hypervolemia, which may ultimately result in pulmonary edema and respiratory compromise. Diuretic use in such patients may be limited by kidney dysfunction and electrolyte abnormalities, including hyponatremia and hypokalemia. A slow, continuous form of ultrafiltration known as aquapheresis is a method of extracorporeal fluid removal whereby a pump generates a transmembrane pressure that forces an isotonic ultrafiltrate across a semipermeable membrane. This leads to removal of an ultrafiltrate that is isotonic to blood without the need for dialysate or replacement fluid as is necessary in other forms of continuous kidney replacement therapy. This technique has been utilized in other conditions including acute decompensated heart failure, with trials showing mixed, but generally favorable results. Herein, we present a series of our own experience using aquapheresis among patients with cirrhosis, review the literature regarding its use in other hypervolemic states, and discuss how we may apply lessons learned from use of aquapheresis in heart failure to patients with end-stage liver disease.

Serum Exosome-Derived microRNA-193a-5p and miR-381-3p Regulate Adenosine 5'-Monophosphate-Activated Protein Kinase/Transforming Growth Factor Beta/Smad2/3 Signaling Pathway and Promote Fibrogenesis.

Liver fibrosis results from chronic liver injury and inflammation, often leading to cirrhosis, liver failure, portal hypertension, and hepatocellular carcinoma. Progress has been made in understanding the molecular mechanisms underlying hepatic fibrosis; however, translating this knowledge into effective therapies for disease regression remains a challenge, with considerably few interventions having entered clinical validation. The roles of exosomes during fibrogenesis and their potential as a therapeutic approach for reversing fibrosis have gained significant interest. This study aimed to investigate the association between microRNAs (miRNAs) derived from serum exosomes and liver fibrosis and to evaluate the effect of serum exosomes on fibrogenesis and fibrosis reversal, while identifying the underlying mechanism. Using serum samples collected from healthy adults and paired histologic patients with advanced fibrosis or cirrhosis, we extracted human serum exosomes by ultrahigh-speed centrifugation. Transcriptomic analysis was conducted to identify dysregulated exosome-derived miRNAs. Liver fibrosis-related molecules were determined by qRT-PCR, Western blot, Masson staining, and immunohistochemical staining. In addition, we analyzed the importance of serum exosome-derived miRNA expression levels in 42 patients with advanced fibrosis or cirrhosis. Exosome-derived miR-193a-5p and miR-381-3p were associated with fibrogenesis, as determined by transcriptomic screening. Compared with healthy control group, the high expression of serum exosome-derived miR-193a-5p and miR-381-3 in chronic hepatitis B (n = 42) was closely associated with advanced liver fibrosis and cirrhosis. In vitro , exosome-derived miRNA-193a-5p and miR-381-3p upregulated the expression of α-smooth muscle actin, collagen 1a1, and tissue inhibitors of metalloproteinase 1 in the human hepatic stellate cell line at both mRNA and protein levels. Serum exosome-derived miR-193a-5p and miR-381-3p regulated the adenosine 5'-monophosphate-activated protein kinase/transforming growth factor beta/Smad2/3 signaling pathway and promoted fibrogenesis.

Real-Life Experience in the Efficacy and Safety of COVID-19 Vaccination in Patients with Advanced Cirrhosis.

COVID-19 infections accelerate liver decompensation and serious liver-related co-morbidities. The aim is to evaluate the safety and impact of COVID vaccines on hepatic disease progression in patients with advanced liver disease and to identify parameters that predict the occurrence of complications. The study involved 70 patients with advanced liver disease who were vaccinated with different COVID vaccines from January 2021 to April 2022. They were evaluated clinically. The laboratory investigation included a complete blood count, liver and kidney function tests, calculation of CTP and MELD scores, plasma levels of ammonia, abdominal ultrasound, and upper GI endoscopy. Twenty patients had experienced complications 64 ± 12 days from the last dose of a vaccination. Twenty patients (28.6%) developed hepatic decompensation and hypothyroidism (n = 11, 15.7%), and five (7.14%) patients developed splanchnic thrombosis. There were no COVID-19 reinfections except for two patients who received Sinopharm and developed vaccine-associated enhanced disease (2.9%). Complications after COVID vaccinations were correlated with ALT (r = 0.279, p = 0.019), serum sodium (r = -0.30, p = 0.005), creatinine (r = 0.303, p = 0.011), liver volume (LV) (r = -0.640, p = 0.000), and MELD score (r = 0.439, p = 0.000). Multivariate logistic regression revealed that LV is the only independent predictor (p = 0.001). LV ≤ 682.3 has a sensitivity of 95.24% and a specificity of 85.71% in predicting complications with an AUC of 0.935, p < 0.001. In conclusion, the hepatic reserve and prognosis in liver cirrhosis should be evaluated prior to COVID vaccinations using the MELD score and liver volume as promising risk stratification criteria. In summary, the research proposes a novel triaging strategy that involves utilizing the MELD score and liver volume as risk stratification parameters of the hepatic reserve and prognosis of advanced liver cirrhosis prior to COVID immunization to determine who should not receive a COVID vaccination.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study

Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. This was a single-center retrospective cohort study. This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

Sodium glucose co-transporter-2 (SGLT) inhibitors in patients with compensated cirrhosis and diabetes: A prospective study

Aims and objective: Diabetes in patients with cirrhosis is common. SGLT-2 inhibitors are newer class of antidiabetic drugs with pleiotropic effects. Its safety and efficacy has not been evaluated in patients with advanced cirrhosis and diabetes. We evaluated safety and efficacy of SGLT-2 inhibitors in patients with compensated cirrhosis and diabetes. Material and method: Consecutive patients with compensated cirrhosis and diabetes who were started on SGLT-2 inhibitors were enrolled and followed every month for six months. Their clinical and biochemical parameters which include liver and kidney function tests, urine test, glycosylated haemoglobin (HbA1c), transient elastography (fibroscan), Mean Arterial Pressure (MAP) and change in weight since treatment initiation were noted. Any relevant side effects (urinary and genital infection, hypotension) were noted. Results: Twenty patients [(M:F: 13:7), age (55±11 yr), CTP score (6±1.3), etiology of cirrhosis (NASH related 17, HBV, n=1 and HCV, n=2), baseline MAP (91±5 mmHg)] were enrolled. Five patients had hypertension and taking angiotensin converting enzyme (ACE) inhibitors and 15 patients were also on carvidelol. Mean Fibroscan was (37±11kPa), large varices (n=3), small varices (n=16) and no varices were seen in one patient. All patients were followed up for 6 months. Patient were on dapagliflogin (n=11, 55%), empagliflogin (n=6, 30%) and remogliflogin (n=3, 15%). Twelve (60%) patients were also on metformin and 7 (35%) on Dipeptidyl peptidase 4(DPP4) inhibitors. Significant improvement was seen in total bilirubin Baseline (B), 1.19±0.5, Month 3 (Mo 3), 1.02±0.4 and Month 6 (Mo 6), 1.01±0.3 mg/dl], AST (B, 50.8±20.8, Mo 3, 49.4±20.5, Mo 6, 42.8±13.0 IU/L) and GGT (B, 63.8±24.5, Mo 3, 66.5±31.0 and Mo 6, 58.3±21.4 IU/dl) level at month 3 and 6. Glycemic index improved at month 3 and 6 and significant weight loss was seen at month 3 and 6. Serum creatinine, serum sodium level and mean arterial pressure remained unchanged at month 6. Urinary tract infection occurred in n=3 (15%), genital infection in (n=2, 10%) and compliant of frothy urine was seen in (n=4, 20%) without discontinuation of medicines.

Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis

Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n= 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n= 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122mm2, p <0.001). The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Сhanges in the composition of gut microbiota in patients with chronic hepatitis С, non-alcoholic fatty liver disease at different stages of liver disease: a review

INTRODUCTION. The human gut microbiota is a set of microorganisms that are in symbiosis with the host organism. The predominance of bacteria of Bacteroidetes, Firmicutes, Actinobacteria types is a characteristic feature of human gut microbiota. However, the composition of the gut microbiota is subject to change under the influence of a number of factors. The influence of the gut-liver axis on the pathogenesis of many chronic liver diseases of various etiologies, both infectious and metabolic, has been proven. At the same time, in the analyzed literature, the data on the relationship between the nature of GM changes and the stage of liver damage are quite controversial.&#x0D; OBJECTIVE. Updating and systematization of ideas about the nature of changes in the composition of intestinal microbiota in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) at different stages of the disease.&#x0D; MATERIALS AND METHODS. We analyzed the scientific literature on GM changes in chronic liver diseases with regard to their etiology and disease stage, in particular in chronic viral hepatitis C and NAFLD. The search was conducted in PubMed, Google Scholar, and eLIBRARY databases for 2000-2023 using the following keywords: gut microbiota; microbiota in hepatitis C; microbiota in NAFLD; microbiota in liver fibrosis; liver fibrosis progression. Sixty scientific articles were analyzed and 42 sources were selected, of which more than 60% were published within the last five years.&#x0D; RESULTS. This review presents the results of original studies describing the main taxonomic differences between the microbiomes of healthy individuals and patients with CHC complicated by the formation of liver cirrhosis and hepatocellular carcinoma (HCC). Thus, patients with viral cirrhosis showed impoverishment of intestinal commensals Lachnospiraceae and Ruminococcaceae and significant enrichment of Streptococcaceae, Lactobacillaceae and Enterobacteriaceae. In patients with non-alcoholic steatohepatitis (NASH) and FII, enrichment of GM Phylum Bacteroides and Proteobacteria, Families Lachnospiraceae and Enterobacteriaceae, Genera Blautia and Escherichia, with a concomitant decrease of Prevotella was detected.&#x0D; DISCUSSION. The analysis of GM taxonomic units in the previously described studies did not reveal significant differences depending on the etiology of the underlying disease. However, a decrease in the representative of the phylum Firmicutes - Ruminococcaceae was observed in CHC in contrast to NAFLD. A more distinct relationship can be observed in the changes of intestinal microbiota in F(III-IV) irrespective of etiology. Thus, in advanced liver fibrosis and cirrhosis of both CHC and NAFLD etiologies, enrichment of GM has been described due to an increase in phylum Proteobacteria, in particular the genus Escherichia and phylum Firmicutes (Blautia, Veillonellaceae). In the studies analyzed, at F(III-IV), an enrichment of the microbiota is observed due to an increase in the phylum Bacteroidetes. Regarding the genus Prevotella, contradictory results were found. In addition, there are ambiguous data regarding the genera Lactobacillus, Ruminococcaceae and Bifidobacteria.&#x0D; CONCLUSION. Based on the results of the literature review, we obtained contradictory data on GM composition in patients with CHC and NAFLD. This may be due to the size of samples, heterogeneity of initial data during the selection of patients in the study. The relationship between the composition of microbiota and persistent inflammatory process, expressed liver fibrosis is observed. GM reflects not only functional disorders in chronic liver diseases of various etiologies, but can also serve as a diagnostic indicator of their progression.

Performance of two-dimensional shear wave elastography for detecting advanced liver fibrosis and cirrhosis in patients with biliary atresia: a systematic review and meta-analysis.

Two-dimensional shear wave elastography (2D-SWE) has been proposed for detecting liver fibrosis in biliaryatresia. To assess the performance of 2D-SWE for detecting advanced liver fibrosis and cirrhosis in patients with biliaryatresia. Five electronic databases were searched to identify studies investigating the performance of 2D-SWE fordiagnosing liver fibrosis in biliary atresia in children. We constructed the summary receiver operating characteristic(SROC) curves of 2D-SWE for detecting advanced liver fibrosis and cirrhosis, and then calculated the area underthe SROC curves (AUROCs). Six studies with 470 patients (ages 55 days to 6.6 years) were included. The median correlation coefficient of 2D-SWEwith pathological liver fibrosis stages was 0.779 (range: 0.443‒0.813). The summary AUROCs for advancedliver fibrosis and cirrhosis were 0.929 and 0.883, respectively. The summary sensitivity and specificity of 2D-SWEfor advanced liver fibrosis were 88% (95% confidence interval [CI]: 80‒94%) and 85% (95% CI: 77‒91%) with I values of 0% and 45.6%, respectively, and for cirrhosis were 80% (95% CI: 72‒87%) and 82% (95% CI: 77‒86%)with I values of 12.9% and 0%, respectively. The diagnostic odds ratio (DOR) of 2D-SWE for advanced liverfibrosis and cirrhosis were 40.3 (95% CI: 18.2‒89.4) and 18.9 (95% CI: 11.2‒31.7), respectively. For preoperativedetection of cirrhosis, the pooled AUROC, sensitivity, specificity, and DOR based on the four 2D-SWE studies were 0.877, 79% (95% CI: 71‒86%), 82% (95% CI: 77‒86%), and 17.58 (95% CI: 10.35‒29.85), respectively. Results show that 2D-SWE has potential as a non-invasive tool for detecting advanced liver fibrosis and cirrhosis in patients withbiliary atresia.

Serum Tsukushi Level Is Associated With the Severity of Liver Fibrosis Independent of Type 2 Diabetes.

Tsukushi (TSK) is a recently identified hepatokine, and we aimed to investigate the association between systemic TSK and the severity of nonalcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes mellitus (DM). Three hundred ninety-three DM and 289 without DM individuals were recruited for transient elastography assessment to determine liver steatosis and fibrosis. Serum TSK was measured by ELISA. The presence of NAFLD was defined as controlled attenuation parameter ≥ 248 dB/m. NAFLD was present in 276 (70.2%) and 129 (44.6%) subjects with and without DM respectively, and they had higher serum TSK levels than those without NAFLD [DM group: 91.0 ng/mL (61.7-133.8) vs 82.5 (60.9-118.5), P < .01 respectively; without DM group: 97.1 ng/mL (69.3-148.6) vs 80.8 (53.4-111.6) respectively, P < .01]. Univariate analysis showed that serum TSK significantly correlated with the degree of steatosis and fibrosis both in subjects with and without DM. On multivariable regression analysis, only liver stiffness and estimated glomerular filtration rate were significant determinants of TSK level, and the relationship was independent of diabetes and serum adiponectin. Out of 405 subjects with NAFLD, 49 had either advanced fibrosis or cirrhosis. The area under receiver operating characteristic curve of serum TSK to indicate advanced fibrosis or cirrhosis was 0.70 (95% CI .62-.77), which was significantly better than that of fibrosis-4 index, 0.64 (95% CI .55-.72), P < .05. Serum TSK levels were increased in subjects with NAFLD and reflected the severity of liver fibrosis.

Metabonomics Application on Screening Serum Biomarkers of Golden Hamsters with Nonalcoholic Steatohepatitis Induced by High-Fat Diet.

Nonalcoholic steatohepatitis (NASH) is a common liver injury which will develop into advanced fibrosis and cirrhosis. This study was designed to identify the different serum metabolites of NASH hamsters and predict the diagnosis biomarkers for NASH. Golden hamsters were randomly divided into a control group that received a normal diet and a NASH group that received a high-fat diet (HFD). After 12 weeks of feeding, the body and liver weight of the hamsters were monitored. Serum biochemical parameters and liver histopathological changes were analyzed. Moreover, an untargeted metabolomics analysis based on a GCTOF/ MS system was performed to identify the serum differential metabolites between the NASH and control groups. The liver weight was increased in the NASH group, accompanied by significantly higher levels of serum TC, TG, ALT, AST, LDL-C, and lower HDL-C. HE, Masson, and oil red O staining showed the hepatocyte structure destroyed, lipid droplets accumulated, and fibers proliferated in the NASH group. Furthermore, 63 differential metabolites were identified by metabolomic analysis. Lipids and fatty acids were significantly up-regulated in the NASH group. The top 9 differential metabolites included cholesterol, methyl phosphate, taurine, alpha-tocopherol, aspartic acid, etc. Metabolites were mainly involved in amino acid metabolism (glycine, cysteine, taurine), spermine, fatty acid biosynthesis, urea cycle, bile acid metabolism pathways, etc. Conclusion: Metabonomics analysis identified 63 differential metabolites in the serum of NASH hamsters; among them, lipids and fatty acids had a key role and may be used as biomarkers for the early diagnosis of NASH.

Individualized Periprocedural and Intraprocedural Management for Coil Embolization of Unruptured Cerebral Aneurysm in a Patient with Severe Thrombocytopenia due to Liver Cirrhosis

A female patient in her early 60's with advanced liver cirrhosis and thrombocytopenia having a platelet count under 30,000/µL, visited an outpatient clinic. Computed tomography angiography revealed an unruptured aneurysm on the left middle cerebral artery bifurcation with 6.0 mm of maximal diameter. Endovascular coiling was planned, considering the patient's medical condition. Eight pints of platelet concentrate were transfused 6 hours before the procedure, and a platelet count of 57,000/ µL was achieved 3 hours before the procedure. No antiplatelet premedication and intraprocedural heparin was administered. A bail-out use of intra- or postoperative Tirofiban (Aggrastat®) was prepared for inadvertent thromboembolic events. The aneurysm was successfully occluded with no procedure-related event. The patient’s hospital course was uneventful, and she was discharged without complications. Despite the potential hemorrhagic risk caused by hemostatic failure in patients with cirrhosis, successful endovascular coiling can be performed with highly individualized management.

Deranged Biochemical Markers As Early Predictors for the Development of Hepatorenal Syndrome in Patients With Alcoholic Liver Cirrhosis.

Objective To investigate predictive biomarkers correlated with the onset of hepatorenal syndrome (HRS) in individuals with alcoholic liver cirrhosis using various factors, including age, sex, and laboratory indicators such as serum sodium, bilirubin, PT/INR, and albumin levels. Additionally, we sought to establish a correlation between the occurrence of hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and the model for end-stage liver disease (MELD) score at the time of diagnosis and the development of HRS in cirrhotic patients. Methods This cross-sectional study spanned 12 months and included a total of 83 patients as its sample size. This study was conducted at the Department of Internal Medicine, a tertiary care hospital situated in Mumbai, India. Two distinct groups were formed: one consisted of patients diagnosed with HRS, and the other group comprised patients with alcoholic liver cirrhosis but without HRS. This study aimed to investigate potential relationships with the suggested risk factors. To discern statistically meaningful distinctions among categorical variables, the chi-square test was employed, whereas for continuous variables, analysis of variance (ANOVA) was used. Only patients who provided written informed consent were included in this study. Results No correlation was found between patients with and without HRS with respect to age (p=0.056) and sex (p=0.067). The presence of HE (p<0.001), SBP (p=0.021), hyponatremia (p=0.0001), hypoalbuminemia (p<0.0001), higher PT/INR (p=0.03), and higher MELD score (p=0.0002) were found to be correlated with an increased risk of developing HRS. Hyperbilirubinemia was not correlated with an increased risk of developing HRS (p=0.157). Conclusions HRS is a severe and potentially avoidable complication associated with advanced liver cirrhosis, characterized by a notably high mortality rate. By closely monitoring key biomarkers, such as serum sodium, PT/INR, and albumin levels, in addition to assessing the presence of SBPand HEduring the initial presentation of patients with alcoholic cirrhosis, medical professionals may be able to identify those at a heightened risk of developing HRS. This, in turn, enables the swift diagnosis and implementation of aggressive treatment strategies. Such measures not only hold the potential to reverse HRSbut also enhance survival rates among individuals with alcoholic liver cirrhosis, thereby increasing the pool of candidates eligible for liver transplantation, which remains the cornerstone of treatment.

Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis.

Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Uncovering the Cardiovascular Threat: A Comprehensive Examination of Liver Fibrosis and Subclinical Atherosclerosis in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global epidemic intricately linked to the rising tide of obesity and metabolic syndrome. This comprehensive review delves into the complex web of relationships between NAFLD, liver fibrosis, and subclinical atherosclerosis, shedding light on their interplay, shared risk factors, and clinical implications. NAFLD encompasses a spectrum of liver conditions, from the benign non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), characterized by inflammation and hepatocellular injury. Central to the discussion is the insidious development of liver fibrosis, the ominous harbinger of progressive liver damage, cirrhosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD, now affecting a quarter of the global population, poses a significant public health challenge. Its association with obesity, insulin resistance, and metabolic syndrome highlights the multifactorial nature of this disease. However, NAFLD's repercussions extend beyond the liver. This review unveils a potent connection between NAFLD and subclinical atherosclerosis, the early precursor to cardiovascular disease. Individuals with NAFLD face an elevated risk of atherosclerosis, even without traditional cardiovascular risk factors. The intricate link between these two conditions is illuminated through shared pathophysiological pathways, including systemic inflammation, insulin resistance, and dyslipidemia. Understanding the interplay between liver fibrosis and subclinical atherosclerosis has profound clinical implications. Patients with advanced fibrosis or cirrhosis are not only at risk of liver-related complications but also of cardiovascular events. This necessitates a holistic approach to patient care, with lifestyle modifications and pharmacological interventions simultaneously managing both conditions. Physicians must prioritize early detection and collaborate across disciplines to provide comprehensive care. Looking ahead, the future holds promising avenues of research. Emerging areas include genetics and precision medicine, microbiome research, and epigenetics, which may unveil new therapeutic targets. Innovations in diagnostics and therapeutics, such as non-invasive biomarkers and combination therapies, offer hope for more effective management. Long-term outcomes and survivorship research will provide insights into the lasting impact of interventions. In conclusion, this review underscores the imperative of addressing liver fibrosis and atherosclerosis in the context of NAFLD. It is a call to action for healthcare professionals, researchers, and policymakers to work collaboratively, promote early detection, and advance our understanding of these interconnected conditions. By doing so, we can enhance patient outcomes and chart a course toward a healthier future for those grappling with NAFLD and its intricate web of consequences.

Clinical and epidemiological characteristics of D hepatitis В and delta in the Republic of Dagestan

Aim: The analysis of the incidence of hepatitis B in the Republic of Dagestan (RD) and clinical and epidemiological characteristics of HBV/HDV coinfection in the region.Materials and Methods. The dynamics of the hepatitis B incidence rates and the coverage of vaccination against this infection in the RD in 2008-2022 were analyzed based on the data from of the statistical forms of Rospotrebnadzor. The clinical and epidemiological characteristics of delta hepatitis were analyzed in 371 patients under dispensary observation at the Republican Center for Infectious Diseases named after S.-А.М. Magomedov.Results. Over the past 10 years, the incidence of CHB in the RD has increased more than 4.5 times, from 1.4 per 100 thousand population in 2008 to 6.7 per 100 thousand population in 2022. A decrease in the rates of hepatitis B child immunization in the RD is observed since 2009. Hepatitis B vaccination coverage rates in adult population fell sharply after 2010, both in the RD and in the Russian Federation on average. The frequency of HDV co-infection in persons infected with HBV in the RD is 13.8%, but reaches 15% in some regions of the republic, indicating the moderate level of endemicity. Patients with HBV/HDV coinfection are predominantly males aged 25–45 years with advanced fibrosis or cirrhosis. All cases of HDV infection in the RD are caused by viral genotype 1.Conclusions. The obtained results testify to the significance of the problem of hepatitis B and delta in the RD. The number of identified patients and, accordingly, the rate of co-infection, apparently, will increase with the expansion of screening for markers of HDV infection, when patients who were registered as HBsAg carriers will be examined according to the patient routing guidelines. The late diagnosis of delta hepatitis in RD and the limited possibilities of antiviral therapy are another significant issues.

Improving palliative and supportive care in advanced cirrhosis: the HepatoCare model of integrated collaborative care.

Patients with advanced cirrhosis experience an unpredictable disease trajectory but are infrequently referred to palliative care (PC) services and rarely undertake advance care planning (ACP). We assessed whether a novel model of care increased provision of meaningful PC in advanced cirrhosis compared with standard of care (SOC). Thirty consecutive hepatology clinic outpatients with advanced cirrhosis, meeting one or more cirrhosis-related PC referral criteria, consented to treatment in the HepatoCare clinic (PC physician, specialist liver nurse, pharmacist) in parallel with usual specialist hepatology care. A control cohort of 30 consecutive outpatients with advanced cirrhosis undergoing SOC treatment was retrospectively identified for comparison. The primary outcome was provision of meaningful PC using HepatoCare versus SOC. Additional clinical outcomes were assessed over 12 months or until death and significant differences were identified. The intervention and control cohorts had similarly advanced cirrhosis (mean Child-Pugh scores 8.7 vs 8.2, P = 0.46; mean model for end-stage liver disease scores 14.4 vs 14.6, P = 0.88) but a lower 12-month mortality rate (33% HepatoCare vs 67% SOC; P = 0.02). The intervention cohort experienced higher uptake of formal ACP (100% vs 25% for the control cohort) and outpatient PC referral (100% vs 40%), and were more likely to die at home or in a PC bed/hospice (80% vs 30%). The majority of the HepatoCare cohort (81%) had medications safely deprescribed and experienced fewer unplanned admission days (470 vs 794). HepatoCare is a novel multidisciplinary model of care that integrates effective PC and specialist hepatology management to improve outcomes in advanced cirrhosis.

Interactions between Metabolic Syndrome, MASLD, and Arterial Stiffening: A Single-Center Cross-Sectional Study.

Metabolic-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), has emerged as a prominent global cause of chronic liver disease and is increasingly recognized as associated with atherosclerotic vascular illness, consolidating its position along traditional cardiovascular risk factors. Individuals with MASLD exhibit a combination of metabolic syndrome risk factors, carotid atherosclerosis, and increased arterial stiffness, hinting at shared pathogenesis. In this study, we aim to explore liver involvement and arterial stiffness within metabolic syndrome. We enrolled 75 patients (30 male and 45 female) with either liver steatosis on conventional ultrasound, altered liver function tests, or the presence of cardiometabolic risk factors after excluding liver pathology other than MASLD. Clinical evaluation, laboratory measurements, abdominal and carotid ultrasounds, vibration-controlled transient elastography (VCTE, Fibroscan), and assessment with the Arteriograph (Tensiomed) were performed. The 26 patients diagnosed with MetS had significantly higher liver involvement as quantified via the hepatic steatosis index (HSI), Fibrosis-4 (FIB4), aspartate aminotransferase to platelet ratio index (APRI) category, and VCTE measurements, as well as Agile 3+ and Agile 4 scores which use a combination of clinical and laboratory parameters together with results obtained from VCTE to reflect the probability of advanced liver fibrosis or cirrhosis. Patients with MetS also exhibited more pronounced vascular involvement as quantified via arterial stiffness measurements and CIMT (carotid intima-media thickness). We applied a two-step clustering algorithm to enhance our analysis, which gave us pertinent insight into the interplay between metabolic syndrome elements and typologies of hepatic steatosis and arterial stiffness degrees. Notably, of the three obtained clusters, the cluster showing increased levels of hepatic steatosis and arterial stiffness also exhibited the highest prevalence of metabolic syndrome and its constituting components. The results have significant clinical implications, advocating for a comprehensive diagnostic approach when MetS or MASLD is suspected.

Performance of noninvasive fibrosis indices in chronic hepatitis B during pretreatment and post-treatment periods.

Background: Pretreatment and post-treatment performances of noninvasive fibrosis indiceswere determined in patients with chronic hepatitis B. Method: This was a retrospective, single-center study. Results: The best area under the receiver operating characteristiccurve valueswere detected foraspartate aminotransferase-to-alanine aminotransferase ratio (0.685) for ≥F2, Fibrosis Index (FI;0.703) for ≥F3; FI (0.872) for ≥F4 and FI (0.864) for cirrhosis. After antiviral treatment, the best area under the receiver operating characteristic curve values were detected in aspartate aminotransferase-to-alanine aminotransferase ratio (0.615) for ≥F2; in FIbased onfour factors (FIB-4;0.634) for ≥F3; in FIB-4 (0.678) for ≥F4 and in FIB-4 (0.814) for cirrhosis. Conclusion: FIB-4 and FI showed better performancein defining advanced fibrosis (≥F4) and cirrhosis.

Pre-Treatment Trends in Child-Pugh Score as an Indicator of Post-Treatment Survival in Patients Receiving Liver SBRT for HCC

We sought to understand the value of Child-Pugh (CP) score trends prior to undergoing stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma in patients with advanced cirrhosis, as an indicator of post-treatment morbidity and mortality. We hypothesize that an uptrend in CP score prior to RT increases risk of post-treatment cirrhosis progression, or death. We retrospectively reviewed all patients who underwent definitive SBRT for HCC between 2014-2022 in our health system. Most patients were referred for treatment in the 2nd or 3rd line setting, allowing us to determine CP score at multiple points before SBRT. Response to treatment was evaluated with RECIST or mRECIST criteria. Acute treatment toxicities were assessed by CTCAE v5. OS was assessed using the Kaplan-Meier method, and differences between groups were evaluated using log-rank test. A total of 61 patients were identified, 26 had an immediate pre-SBRT CP score of A5, 11 with A6, 10 with B7, 4 with B8, 4 with B9, 5 with C10, and 1 with C11. Median prescribed dose was 40Gy in 5fx. Median OS of all patients was 24 months. When stratified by CP category, median OS for CP A was not reached (NR) at time of analysis, CP B had a median OS of 14.8mo, and CP C with 1.9mo (p < 0.01). Local control rate at 6mo was 87.5%. 5 patients (8.3%) had CTCAE grade 2 acute toxicity. 10 patients had CP score progression of 2pts or more within 6mo after treatment, and 7 patients had a cause of death attributed to end stage liver disease. Median time interval between HCC diagnosis and start of RT was 338 days. In this time interval, patients with a CP score increase of 2 pts or more prior to starting RT had a median OS of 362 days, compared to NR for patients without increase (p = 0.02). When excluding the CP A group, patients with 2 pt increase had median OS of 362 days vs 445 days (p = 0.34). Again excluding the CP A group, patients with a 1 pt increase had median OS of 362 days vs NR (p = 0.23). Of 9 patients who had a pre-RT CP score increase of 2 pts or more, 7 experienced continued CP progression after treatment. In this multi-institutional retrospective analysis, we found 24 patients with advanced CP B/C cirrhosis who underwent SBRT, none of whom received orthotopic liver transplant. While CP C patients did relatively poorly, we find that some patients with CP B cirrhosis may tolerate SBRT well with good oncologic effect. When taking pre-treatment CP score increase into consideration, we saw a trend but no statistical significance indicating that a pre-SBRT increase in CP score may be associated with worse OS after treatment among CP B/C patients. We conclude that there may be a subset of patients with advanced cirrhosis who, if well selected, are appropriate candidates for SBRT. We suggest a novel use of the CP score and pre-RT trends as an additional clinical tool to aid in decision making when selecting patients. We also suggest that patients with marked up-trending scores pre-treatment have a high likelihood of continued cirrhosis progression after treatment.