Cirrhotic Patients Research Articles

Study of the role of D-dimer in the prediction of hepatorenal syndrome in cirrhotic Egyptian patients

Study of the role of D-dimer in the prediction of hepatorenal syndrome in cirrhotic Egyptian patients

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Long-term outcome following liver transplantation of patients with ACLF grade 3

Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included in a three-centre retrospective French study published in2017. All patients with ACLF-3 (n= 73), as well as their transplanted matched controls with ACLF-2 (n= 145), 1 (n= 119) and no ACLF (n= 292), who participated in the Princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survival rates, causes of death and their predictive factors. Median follow-up of patients with ACLF-3 was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patient survival rates were 72.6% vs. 69.7% vs. 76.4% vs. 77.0%, respectively (p= 0.31). Ten-year patient survival for ACLF-3 was 56.8% and was not different to other groups (p= 0.37). Leading causes of death in patients with ACLF-3 were infections (33.3%) and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and CLIF-C ACLF score were independently associated with 10-year patient survival. Long-term graft survival rates were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. 5- and 10-year patient and graft survival rates were not different in patients with ACLF-3 compared to matched controls. 5-year patient survival is higher than the 50%-70% threshold defining the utility of a liver graft. Efforts should focus on candidate selection based on comorbidities, as well as the prevention of infection and cardiovascular events. While short-term outcomes following liver transplantation in the most severely ill patients with cirrhosis (acute-on-chronic liver failure grade 3 [ACLF-3]) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favourable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in patients with ACLF-3 compared to matched patients with ACLF-2, ACLF-1, and no-ACLF. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidity evaluation, such as the age-adjusted Charlson comorbidity index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding whether to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and tightly managing cardiovascular risk over time.

Evaluation of renal resistive index and new biomarkers in post-hepatitis C cirrhosis patients for developing kidney injury

Background In liver cirrhosis, hemodynamic changes in splanchnic and systemic circulations are involved. Indeed, no established laboratory markers for altered renal hemodynamics in cirrhosis were implicated. The duplex Doppler waveform analysis of intrarenal arteriolar vessels is considered a noninvasive estimate of renovascular impedance and renal arterial vasoconstriction. In particular, the renal resistive index (RRI) is considered as the best reliable indicator of renal blood flow in patients with different diseases. The study aimed to evaluate RRI, serum and urinary cystatin C, beta-trace protein, liver fatty acid protein, and kidney injury molecule-I as noninvasive indicators of altered renal hemodynamics in patients with cirrhosis with normal urea and creatinine. Patients and methods A case–control study included 60 patients with post-hepatitis C virus (HCV) cirrhosis and 40 healthy controls. Serum and urinary biomarkers were measured. Renal color Doppler duplex was used to evaluate RRI. Results Mean serum and urinary biomarkers in HCV patients were significantly higher than controls. Moreover, the RRI was higher in patients than in controls with P value less than 0.001. Rising levels of urea, high direct bilirubin, and hypoprothrombinemia with high serum kidney injury molecule 1 and RRI were significant independent predictors for subsequent kidney injury. Conclusion Urinary kidney injury molecule 1 is a reliable, sensitive, and specific biomarker for the prediction of kidney injury among HCV cirrhotic patients with an obvious superior test performance and specificity to e other biomarkers. An increase in serum kidney injury molecule 1 and RRI were associated with poor prognosis.

Utility of Hemogram-based Parameter in Predicting Hospital Stay in Liver Cirrhosis: A 2-year Prospective Observational Study

Abstract Introduction: Hospitalized cirrhosis patients are a major financial burden on health-care systems. In this study, we attempted to evaluate the regular laboratory parameter like absolute eosinophil count (AEC), in liver cirrhosis in relation to length of hospital stay and severity grading systems such as the Child–Turcotte–Pugh (CTP) score and the model for end-stage liver disease (MELD). Materials and Methods: A prospective observational study was done in patients at a rural tertiary care hospital in central India, from October 2019 to September 2020. Calculation of AEC was done by automated complete blood counts in hemogram. Demographics of the patient, laboratory investigations, and outcomes of hospital stay were taken into consideration in the study. To identify predictors of hospital stay, a multivariate Cox regression analysis was used. Results: Among hemogram, with a cutoff value of ≤138, the AEC was found to be a significant predictor of lengthy hospital stays (≥7 days), with a 63.70% likelihood of properly predicting such stays. If AEC ≤138, then there was a 69.80% probability of prolonged hospital stays. Distribution of CTP score was comparable between hospital stay duration, i.e. &lt;7 days and ≥7 days. Proportion of patients with MELD score with ≤9, was significantly higher if duration of hospital stay was &lt;7 as compared to hospital stay duration ≥7 in MELD score 10-19. Conclusions: In hospitalized cirrhotic patients, among the hemogram, the AEC may be used as a low-cost warning indicator for clinical outcomes such as hospital stay.

MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis

Background and AimsDespite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic liver remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods354 patients with MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018, were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results35% of HCC cases occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Non-cirrhotic patients were older, had a greater tumor burden, but also better liver function than cirrhotic patients. Non-cirrhotic patients showed better overall survival than those with cirrhosis (p=0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Non-cirrhotic patients underwent surgery more frequently than cirrhotic patients did (41% versus 11%, p<0.001), even in cases where the largest tumors were ≥5 cm (42% versus 14%, p=0.002) or there were four or more lesions (19% versus 2%, p=0.024). Among the cirrhotic and non-cirrhotic patients who underwent surgery, survival was not significantly different. The cirrhosis / no cirrhosis ratio remained stable over the study period. ConclusionsIn MASLD-related HCC, non-cirrhotic patients account for 35% of cases and have poor prognostic factors (higher age and larger tumors) but also better liver function, resulting in more aggressive management of advanced tumors and better survival compared to cirrhotic patients. Impact and implicationsThe incidence of hepatocellular carcinoma related to MASLD is projected to increase by 47% to 130% by year 2030 with one third occurring in non cirrhotic livers, making them inaccessible to screening with tumors more advanced at diagnosis. Our study shows that survival in MASLD patients with hepatocellular carcinoma relies on age, tumor burden and underlying liver function and the preserved liver function of these non-cirrhotic patients allows them to be managed surgically. A better understanding of the pathophysiological processes driving HCC occurrence in non-cirrhotic MASLD patients to screen and early management of these patients.

Pulmonary Vascular Permeability and Extravascular Lung Water Index in Patients with Liver Cirrhosis and Septic Shock.

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.

Character and Frequency of the Syntropic Extrahepatic Lesions in Cirrhotic Patients with Hepatopulmonary Syndrome of Various Severity Degree

Introduction. All over the world, and in Ukraine in particular, the incidence of liver diseases is constantly increasing. By practicing the most effective individualized appointment of complex treatment, it should be taken into consideration the involvement of different organ systems to the pathological processes of the cirrhotic patients, which we define as syntropic polymorbid lesions. The aim of the study. To determine the frequency and character of syntropic extrahepatic lesions in cirrhotic patients depending on the hepatopulmonary syndrome severity degree. Materials and methods. In a randomized manner with preliminary stratification by the presence of hepatopulmonary syndrome were studied 93 patients with liver cirrhosis, who underwent the comprehensive clinical-laboratory and instrumental examination. Results. According to the obtained results, most often in patients with liver cirrhosis associated with hepatopulmonary syndrome syntropic extrahepatic lesions affected other organ systems as follows: digestive system - 100.0 % patients under investigation; hematopoietic system - 84.9 %; nervous system - 81.7 %; integumentary system and mucous membranes - 78.5 %; blood circulatory system - 76. 3%;osteoarticular system - 67.7 %; urinary system - 22.6 %. Increased severity of hepatopulmonary syndrome significantly (p &lt; 0.05) correlated with thein creased frequency of lesions. Among syntropic polymorbid lesions of the integumentary system and mucous membranes, 68.8 % patients with hepatopulmonary syndrome had jaundice, 66.7 % - telangiectasia. Among lesions of the osteoarticular system osteopenia was diagnosed in 44.7 % of patients, osteoporosis - in 27.7 %. Among lesions of the circulatory system 52.7% of patients suffered from heart rhythm disorders, 49.5 % - from arterial hypotension, 20.4 % - from cirrhotic cardiomyopathy. Among lesions of the hematopoietic system anemia (76.3 %), coagulopathy (73.1 %) and thrombocytopenia (61.3 %) were diagnosed most often. Digestive system lesionsinclude esophageal veins varicosities (94.6 % of patients), hemorrhoidal veins varicosites (68.8 %), and cirrhotic gastropathy (62.4 %). Among lesions of the urinary systemin 21.5 % of patientswas diagnosed type II hepatorenal syndrome. Among the lesions of central nervous system in 81.7 % of patientswas diagnosed hepatic encephalopathy. The frequency of syndromes and nosological units increased significantly (p &lt; 0.05) with the increase of hepatopulmonary syndrome severity. Conclusions. 100.0 % patients with liver cirrhosis accompanied byhepatopulmonary syndromewere affected by syntropic polymorbid lesionsof the digestive system, 94.6 % of which were represented by esophageal vein varicosites. Out of 84.9 % of patients with hematopoietic lesions anemia was diagnosed in 76.3 %, coagulopathy - in 73.1 % of cases. Of total 81.7 % patients withnervous system injurieshepatic encephalopathy was diagnosed in 81.7 % patients. In 78.5 % cases of damaged skin, its appendages and mucous membranesjaundice covered 68.8 %, and telangiectasia 66.7 % of cases. In 76.3 % of cardiovascular system lesions arrhythmias were diagnosed in 52.7 %.With the increasing severity of hepatopulmonary syndrome, the frequency of the above lesions increased significantly (p &lt; 0.05).

Metabolomics reveals altered metabolites in cirrhotic patients with severe portal hypertension in Tibetan population.

Portal hypertension (PHT) presents a challenging issue of liver cirrhosis. This study aims to identify novel biomarkers for severe PHT (SPHT) and explore the pathophysiological mechanisms underlying PHT progression. Twenty-three Tibetan cirrhotic patients who underwent hepatic venous pressure gradient (HVPG) measurement were included. Eleven patients had an HVPG between 5 mmHg and 15 mmHg (MPHT), while 12 had an HVPG ≥16 mmHg (SPHT). Peripheral sera were analyzed using liquid chromatograph-mass spectrometer for metabolomic assessment. An additional 14 patients were recruited for validation of metabolites. Seven hundred forty-five metabolites were detected and significant differences in metabolomics between MPHT and SPHT patients were observed. Employing a threshold of p < 0.05 and a variable importance in projection score >1, 153 differential metabolites were identified. A significant number of these metabolites were lipids and lipid-like molecules. Pisumionoside and N-decanoylglycine (N-DG) exhibited the highest area under the curve (AUC) values (0.947 and 0.9091, respectively). Additional differential metabolites with AUC >0.8 included 6-(4-ethyl-2-methoxyphenoxy)-3,4,5-trihydroxyoxane-2-carboxylic acid, sphinganine 1-phosphate, 4-hydroxytriazolam, 4,5-dihydroorotic acid, 6-hydroxy-1H-indole-3-acetamide, 7alpha-(thiomethyl)spironolactone, 6-deoxohomodolichosterone, glutaminylisoleucine, taurocholic acid 3-sulfate, and Phe Ser. Enzyme-linked immunosorbent assay further confirmed elevated levels of sphinganine 1-phosphate, N-DG, and serotonin in SPHT patients. Significant disruptions in linoleic acid, amino acid, sphingolipid metabolisms, and the citrate cycle were observed in SPHT patients. Pisumionoside and N-DG are identified as promising biomarkers for SPHT. The progression of PHT may be associated with disturbances in lipid, linoleic acid, and amino acid metabolisms, as well as alterations in the citrate cycle.

Cystatin C/albumin ratio for early diagnosis of esophageal varices in liver cirrhosis.

The mortality rate related to variceal bleeding is high in patients with liver cirrhosis. Early detection and treatment of varices can reduce the risk of hemorrhage and thus decrease the mortality rate related to variceal bleeding. The study comprised 81 cirrhotic patients in training set, who were categorized into 2 groups: the patients with esophageal varices (EVs group) and the patients without esophageal varices (non-EVs group). The disparity in Cystatin C/albumin ratio (CAR) was assessed between these 2 groups. Subsequently, a regression model was constructed by generating a receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC). Then an external validation was performed in 25 patients. Among patients with cirrhosis in training set, a statistically significant difference in CAR was observed between the EVs group and non-EVs group (P < .05). At the CAR cutoff value of 2.79*10-5, the AUC for diagnosing EVs were 0.666. Further, a multivariate logistic regression model was constructed, after adjusting the model, the AUC for EVs diagnosis were 0.855. And the external validation showed that the model could not be considered as a poor fit. CAR exhibits potential as an early detection marker for EVs in liver cirrhosis, and the regression model incorporating CAR demonstrates a strong capability for early EVs diagnosis.

Pathomorphology of severe Grade 3-4 hepatic encephalopathy in decompensated cirrhosis patients with acute-on-chronic liver failure

The study was aimed to determine of the most significant pathomorphological signs of severe hepatic encephalopathy (HE) in deceased cirrhotic patients with acute-on-chronic liver failure (ACLF) syndrome based on changes of the glioneuronal complex and the level of tissue ammonia. Using pathohistological, histochemical, and immunohistochemical methods, the cerebral cortex, thalamus, striatum, and cerebellum of 21 deceased patients with acutely decompensated liver cirrhosis with ACLF syndrome and HE Grade 3-4 were examined in comparison with control group, which included 30 deceased patients from acute cardiovascular failure. The study revealed that during HE Grade 3-4 as a component of ACLF, in all studied brain regions, there was a reliably (p&lt;0.05) higher histochemical level of tissue ammonia (up to 500%), increased numbers (up to 215.69%) of apoptotic neurons (according to caspase-3), reduced (up to 119.60%) level of synaptophysin, increased expression of glutamine synthetase (up to 253.02%) and aquaporin-4 (up to 481.81%) associated by reduced (up to 296.81%) expression of glial fibrillary acidic protein in astrocytes, increased (up to 11-fold) numbers of Alzheimer type 2-astrocytes, expansion of perivascular and pericellular «edematous» spaces (up to 890.81%), increased numbers of amyloid bodies (up to 5-fold), increased area of immunopositive material of CD68+ microgliocytes (up to 114.78%) with an increase (up to 71.91%) in the proportion of CD68+ amoeboid microglia. The above-mentioned changes confirm that the loss of consciousness and other psychoneurological manifestations of severe HE Grade 3-4 are due to compound am­monia-associated changes in the components of the glioneuronal complex, namely: adaptive remodeling and dystro­phic changes in astrocytes, reduced synaptic transmission and apoptotic neuronal death, reactive changes in microglia with a small proportion of microgliocytes involved in phagocytosis, cytotoxic brain edema and dysfunction of the glymphatic system

Safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy associated with spontaneous portosystemic shunts

This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 μmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Vaccination in Patients with Liver Cirrhosis: A Neglected Topic.

Patients with liver cirrhosis, due to their weakened innate and adaptive immunity, are more prone to frequent and severe vaccine-preventable infections. Moreover, impaired adaptive immunity results in a limited antibody response to vaccines. Despite this suboptimal antibody response, vaccines have proven to be very effective in reducing severe outcomes and deaths in these patients. In the Western world, regulatory authorities and scientific liver societies (e.g., AASLD and EASL) have recommended vaccinations for cirrhotic patients. However, despite these strong recommendations, vaccine coverage remains suboptimal. Improving vaccine effectiveness and safety information, providing comprehensive counseling to patients, fact-checking to combat fake news and disinformation and removing barriers to vaccination for disadvantaged individuals may help overcome the low coverage rate. In view of this, vaccines should be administered early in the course of chronic liver diseases, as their efficacy declines with the increasing severity of the disease.

Pathogenesis and clinical features of severe hepatitis E virus infection

The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.

Prescription patterns of statins in cirrhotic patients: a survey among primary care physicians and cardiologists

Background Statin therapy is widely utilized for preventing atherosclerotic cardiovascular disease, both as a primary and secondary measure. Despite the American Association for the Study of Liver Diseases’ endorsement of statin use in cirrhotic patients, practitioners exhibit hesitancy, primarily due to concerns regarding hepatotoxicity. This study aimed to evaluate statin prescription patterns in cirrhotic patients by primary care physicians (PCPs) and cardiologists through a survey. Methods A voluntary survey via Survey Monkey with nine objective-type questions was sent to 220 PCPs and 75 cardiologists within Allegheny Health Network. Survey results were collected, and a chi square test was used to compare the two groups. A P value ≤ 0.05 was considered statistically significant. Results A total of 64 PCPs (29.1%) and 15 cardiologists (20%) completed the survey. Overall, 12.6% did not prescribe statins for primary prevention of atherosclerotic cardiovascular disease in compensated cirrhotic patients. While all cardiologists prescribed statins for secondary prevention, over 50% preferred lower-intensity options. Conversely, 14.1% of PCPs avoided statin prescriptions for secondary prevention. Cardiologists were significantly more inclined to prescribe statins, especially for cirrhosis due to metabolic dysfunction-associated steatotic liver disease compared to PCPs (73.3% vs 45.3%, P = 0.05). Conclusions Despite increasing evidence favoring use of statins in cirrhosis for improving portal hemodynamics and decreasing ascites, hepatic encephalopathy, the incidence of hepatocellular carcinoma, and mortality, there is still hesitation on the part of prescribers for the fear of worsening liver disease. Wider dissemination of current guidelines and education practices may help to bridge this gap.

Clinical management of thrombocytopenia in cirrhosis

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

Frailty in liver transplantation: Exploring prescribing exercise as medicine to improve patient outcomes.

Liver transplantation (LT) represents a curative avenue for individuals with advanced chronic liver disease. Given the inherent illness severity of LT candidates, identifying patients at greater risk for adverse outcomes before and after transplantation is paramount. Approximately 50% of cirrhotic patients are frail and have considerable functional impairment. Various measures have been used to assess frailty, including performance-based tests and functional status evaluations. Frailty carries significant prognostic implications and predicts both mortality and pre- and post-LT complications. Contributing factors to frailty in this population include sarcopenia, malnutrition, inflammation, and psychosocial factors. Recognizing the prevalence of frailty among LT candidates, exercise interventions have been developed to improve physical frailty and offer potential to improve patient outcomes. While many interventions have demonstrated efficacy without notable adverse events, the absence of a universally accepted standard for exercise prescription underscores the variability in intervention elements and patient adherence. Given the safety profile of exercise interventions, there remains a critical need for standardized protocols and guidelines to optimize exercise regimens for LT candidates. This review delves into the landscape of frailty among LT candidates, elucidating its etiological underpinnings, impact on outcomes, utilization of exercise interventions, and the efficacy of exercise programs in reducing the burden frailty in those awaiting LT.

Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension

Backgrounds & aimsPortal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-Hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in portal vein (PV) on PH. MethodsPH models were induced by thioacetamide (TAA) injection, bile duct ligation (BDL) or partial portal vein ligation (PPVL). HTR1A expression was detected using real-time PCR, in situ hybridization and immunofluorescence staining. In situ intraportal infusion was employed to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a knock-out (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a knock-out (Htr1aΔVSMC) mice were utilized to confirm the regulatory role of HTR1A on PP. ResultsHTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased but WAY-100635 decreased PP in rats, without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMCs-specific Htr1a knock-out in mice prevented the development of PH. Moreover, 5-HT triggered the cAMP pathway-mediated PVSMCs contraction via HTR1A in PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in TAA-, BDL-, and PPVL-induced portal hypertensive rats. ConclusionsOur findings reveal that 5-HT promotes PH by inducing the contraction of PV, and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia.

The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy. Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.