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Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child–Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients. [ABSTRACT FROM AUTHOR]

Although high mortality is associated with liver cirrhosis, patients usually have a good quality of life in the compensated phase, and the disease may progress undiagnosed for many years. Vibration-controlled transient elastography with controlled attenuation parameter is a useful noninvasive tool used to estimate both the severity of fibrosis and steatosis. Hence, we aimed to establish the prevalence of significant liver fibrosis diagnosed by vibration-controlled transient elastography in an apparently healthy population. Between December 2021 and March 2022, we conducted a prospective screening of liver fibrosis in apparently healthy participants from different counties of Northeastern Romania. All subjects' medical history was recorded through a comprehensive questionnaire and underwent a liver stiffness measurement. Participants with abnormal liver stiffness measurement values were further evaluated by laboratory tests to identify the etiology of chronic liver disease. A total of 127 apparently healthy subjects were enrolled, mainly females (59.8%), with a mean age of 56 ± 11 years. Overall, 12.6% of participants were found to have significant to advanced fibrosis, and 5.4% had liver cirrhosis. Among 184 participants with clinically significant fibrosis (= 8.0 kPa), 26.1% had a history of heavy alcohol intake, 22.3% tested positive for hepatitis B and C infection, and 2.1% with other etiologies. The remaining 49.5% participants with clinically significant fibrosis were diagnosed with NAFLD, with a mean controlled attenuation parameter value of 282±34 dB/m. The high prevalence of significant liver fibrosis in the general population of Romania is alarming and should raise awareness among clinicians and public health systems. Vibration-controlled transient elastography has demonstrated its usefulness as a screening tool to identify advanced liver fibrosis in general population and should be used in liver disease prevention strategies. [ABSTRACT FROM AUTHOR]

Alcoholic liver cirrhosis (ALC) is a disease with multiple complications and is associated with poor prognosis and significant mortality. Identifying risk factors associated with a poor outcome is important to ensure effective treatment and increase life expectancy. We aimed to evaluate the predictive values of complications regarding mortality in ALC. We retrospectively analyzed 1429 patients with ALC hospitalized between January 2019 and April 2022 at the Institute of Gastroenterology and Hepatology Iasi. The electronic medical records were interrogated to obtain information about demographic data, complications, comorbidities, and prognostic scores: MELD-Na (model for end-stage liver disease-sodium) and CTP (Child–Turcotte–Pugh). Based on uni- and multivariate analysis, independent predictors of mortality were identified. The mean age at diagnosis was 56.15 ± 11.49 years with a ratio of 2:1 in favor of males. There were 296 deaths (20.8%), most of them during the first hospitalization (208/14.6%). It was observed during the univariate analysis that complications of the disease negatively affected the survival rate, significant values being related to infections (sepsis; OR = 21.98; p < 0.001; spontaneous bacterial peritonitis (SBP) (OR = 11.94; p < 0.001) and hepatorenal syndrome (HRS) (OR = 9.35; p < 0.001). The independent predictors, confirmed by multivariate analysis, were the association of variceal bleeding, infections, and hepatic encephalopathy or ascites, each combination being responsible for two out of 10 of the deaths during the first admission. The prognosis of the disease was negatively influenced by the worsening of liver dysfunction and the appearance of complications. The main predictors of mortality were infections, hepatic encephalopathy, variceal bleeding, and hepatorenal syndrome. Improving compliance and strict application of specific follow-up and treatment strategies could contribute to a better prognosis of patients with alcoholic liver cirrhosis. [ABSTRACT FROM AUTHOR]

Infections and sepsis represent severe liver cirrhosis (LC) complications and the precipitating factors of hepatic encephalopathy (HE). The early diagnosis and treatment of infections in patients with LC and HE can significantly increase their survival. Presepsin is a serum biomarker evaluated for the early diagnosis of infections and sepsis in the general and cirrhotic populations. This study aimed to evaluate the role of presepsin in the early diagnosis of infections in patients with LC and HE. This prospective observational study included all consecutive cirrhotic patients admitted to our tertiary university center with overt HE. The patients were follow-up until discharge. In this study, we included 365 patients with a median age of 59 years, of whom 61.9% were male. Infections were diagnosed in 134 patients (36.7%). The presepsin level was higher in patients with infections than those without infections (3167 vs. 500, p < 0.001). The ROC analysis results demonstrated that the best cut-off value for presepsin in infections detection was 980 pg/mL with a sensitivity of 80.17%, specificity of 82.5% (AUROC 0.869, CI 95%: 0.819–0.909, p < 0.001, Youden index J of 0.622), a positive predictive value of 40.63%, and a negative predictive value of 96.53%. In conclusion, in patients with LC and overt HE, presepsin levels >980 pg/mL could enhance the suspicion of bacterial infections. Presepsin may be an adequate non-invasive tool for the early diagnosis of infections in patients with LC and overt HE. [ABSTRACT FROM AUTHOR]

The link between heart and liver cirrhosis was recognized decades ago, although much data regarding atherosclerosis and ischemic heart disease are still missing. Ischemic heart disease or coronary artery disease (CAD) and liver cirrhosis could be associated with characteristic epidemiological and pathophysiological features. This connection determines increased rates of morbidity and all-cause mortality in patients with liver cirrhosis. In the era of a metabolic syndrome and non-alcoholic fatty liver disease pandemic, primary prevention and early diagnosis of coronary artery disease could improve the prognosis of liver cirrhosis patients. This review outlines a summary of the literature regarding prevalence, risk assessment and medical and interventional treatment options in this particular population. A collaborative heart–liver team-based approach is imperative for critical management decisions for patients with CAD and liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sarcopenia is commonly associated with liver cirrhosis and predicts clinical outcome. Our aim was to identify the changes in skeletal muscle index (SMI) on computed tomography (CT) examination, as a quantitative marker of sarcopenia, in patients with HCV-related cirrhosis after direct acting antivirals (DAAs) treatment and to assess predictive factors for the evolution of SMI. Materials and Methods: This is a single center retrospective study in patients with HCV-related compensated cirrhosis who obtained sustained virological response (SVR) after DAAs. CT examinations were performed in 52 patients before and within 5–24 months after treatment. The total muscle area (TMA) of abdominal muscle at the level of third lumbar vertebra (L3) was measured at baseline and after SVR. The L3-SMI was calculated from TMA divided by body height squared (cm²/m² ). We assessed changes in L3-SMI after SVR according to baseline body mass index (BMI) and laboratory data. Predictive factors were assessed by linear regression model. Results: Patients with L3-SMI above the gender-specific cut-off value at baseline had higher values of serum creatinine (median 0.73) compared to patients with low L3-SMI (median 0.68, p = 0.031). After SVR, 14 patients showed increase of L3-SMI, and 38 patients had a decrease of L3-SMI. BMI in the decreased L3-SMI group was significantly lower (median 26.17) than those without decreased L3-SMI (median 28.84, p = 0.021). ALT values in the decreased L3-SMI group (median 66.5) were significantly lower than those without a decrease in L3-SMI (median 88, p = 0.045). Conclusions: Low creatinine serum level correlates with sarcopenia. SMI was partially influenced by the viral clearance. Lower BMI and ALT serum levels at baseline were predictive for no benefit in terms of muscle mass dynamics. Understanding all the mechanisms involved in sarcopenia and identifying the most vulnerable patients could ensure optimal adapted care strategies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Antibiotic prophylaxis is effective but can lead to an increased incidence of Clostridioides difficile infection (CDI). The aim of this study was to evaluate the incidence of CDI and the risk factors in cirrhotic patients with a previous episode of SBP receiving norfloxacin as secondary prophylaxis. Materials and Methods: We performed a prospective, cohort study including patients with liver cirrhosis and SBP, successfully treated over a 2-year period in a tertiary university hospital. All the patients received secondary prophylaxis for SBP with norfloxacin 400 mg/day. Results: There were 122 patients with liver cirrhosis and SBP included (mean age 57.5 ± 10.8 years, 65.5% males). Alcoholic cirrhosis was the major etiology accounting for 63.1% of cases. The mean MELD score was 19.7 ± 6.1. Twenty-three (18.8%) of all patients developed CDI during follow-up, corresponding to an incidence of 24.8 cases per 10,000 person-years. The multivariate Cox regression analysis demonstrated that alcoholic LC etiology (HR 1.40, 95% CI 1.104–2.441, p = 0.029) and Child-Pugh C class (HR 2.50, 95% CI 1.257–3.850, p = 0.034) were independent risk factors for CDI development during norfloxacin secondary prophylaxis. The development of CDI did not influence the mortality rates in cirrhotic patients with SBP receiving norfloxacin. Conclusions: Cirrhotic patients with SBP and Child-Pugh C class and alcoholic liver cirrhosis had a higher risk of developing Clostridioides difficile infection during norfloxacin secondary prophylaxis. In patients with alcoholic Child-Pugh C class liver cirrhosis, alternative prophylaxis should be evaluated as SBP secondary prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of HCC following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11-3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%)had a single tumor, 12 patients (52.2%)were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3-93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL). [ABSTRACT FROM AUTHOR]

Introduction. Hepatitis C virus may cause chronic liver infection which may progress to advanced fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). Eradication of HCV could reduce the risk of liver cirrhosis, HCC and liver-related deaths. Interferon-free (IFN-free) treatment can achieve high sustained virological response (SVR) rates, even in patients with one or more comorbidities. Objectives. We want to verify the influence of comorbidities and their treatment on the initiation and performing genotype-specific IFN-free therapy and also on obtaining SVR in these patients. Material and Methods. We made a retrospective study on 85 patients with chronic C infection - 63 female and 22 men (sex ratio 2.86/1), aged between 45 and 80 years old, with median age 62 ± 2.3 years old, hospitalized in "St Spiridon" Hospital Iasi - Gastroenterology between 2019 - 2021 in order to initiate IFN-free therapy. Distribution of the group according to comorbidities: cardiovascular disease - 46 patients (58,8%), diabetes - 8 patients (9,4%), 9 patients - endocrinological disorders (10,5%), 5 patients psychiatric diseases (5,8%), 2 patients respiratory diseases (2,35%), 4 patients hematological diseases (4,7%), 2 patients - neoplastic antecedents (cured gastric neoplasia) 2,3%, 4 patient neurological diseases (4,7%), 5 patients without associated disease (5,8%). The drug interactions were checked and the therapeutic schemes were modulated accordingly. 57 patients (67%) presented F1-F3 grade of fibrosis and 28 patients (32,9%) F4, of which 6 (7%) with decompensated cirrhosis. The associated treatment consisted of: antihypertensives, levothyroxine, insulin therapy, antidepressants, antiparkinsonian, antipsychotics, antidementia. Genotype-specific IFN-free therapy was: Viekirax-Exviera (ombitasvir, pari, ritonavir +dasabuvir) in 46 patients (55,42%), Harvoni (ledipasvir/sofosbuvir) in 26 patients ((31,32%) and Zepatier (Grazoprevir) - 11 patients (13,25%). Results. Out of the 85 patients, 2 with neurological pathology could not initiate the therapy (2,3%). 83 HCV patients (97,64%) started IFN-free treatment. One patient developed severe heart failure and needed to stop IFN-free treatment after six weeks administration (1,17% of total). 82 patients started and finished IFN-free treatment (96,4%). All of them achieved sustained SVR at 12 weeks after treatment (100%). Conclusion. Despite the presence in patients with HCV chronic infection of various comorbidities along with their treatments, IFN-free therapy could be initiated and followed in the vast majority of them. In our study, all patients which started and finished IFN-free regimens obtained SVR. Close monitoring and careful attention are needed to handle unexpected adverse events. [ABSTRACT FROM AUTHOR]