Non-cirrhotic Chronic Liver Disease Research Articles

Role of splenic hepatic elastography ratio in differentiating non-cirrhotic portal fibrosis and chronic liver disease in children and adolescents.

Differentiation of Non-cirrhotic Portal Fibrosis (NCPF) from chronic liver disease (CLD) in children and adolescents with portal hypertension (PHT) is challenging especially in cases where liver stiffness measurement (LSM) and hepatic venous pressure gradient are higher. This objective of the current study was to evaluate the diagnostic accuracy of the splenic stiffness measurement (SSM)/LSM ratio in the diagnosis of NCPF. From January 2019 to December 2023, consecutive children and adolescents of 6months to 18years of age with PHT (CLD and NCPF) were prospectively enrolled. Transient elastography (TE) for SSM and LSM, upper gastrointestinal endoscopy (UGIE), liver biopsy/trans-jugular liver biopsy, abdominal imaging, and laboratory evaluation were done. The relationship of TE parameters for diagnosis of NCPF and CLD was evaluated. Receiver-operating characteristic (ROC) statistics were applied using R Studio-4.2.2 statistical software. One hundred and forty seven with CLD and 27 patients with NCPF were evaluated. Median age was 10.0 (IQR 2.4-14.0) years; 68.4% were males. The AUROC of SSM/LSM ratio was better (0.992, 95%CI 0.982-1.0001) than LSM (0.945, 95%CI0.913-0.977) and SSM (0.626, 95%CI0.258-0.489) for the diagnosis of NCPF. SSM/LSM ratio cut-off of 3.67 predicted NCPF with an excellent sensitivity (100%), specificity (95.9%), and diagnostic accuracy (95.91%). The AUROC of SSM/LSM ratio was excellent and outperformed other TE parameters in the subgroups, i.e., LSM between 10 and 20kPa (0.982, 95%CI 0.947-1.000), without clinically significant varices (CSV) (1.000, 95%CI 1.000-1.000) and with CSV (0.993, 95%CI 0.983-1.000). Diagnostic performance of SSM/LSM Ratio was better than LSM for discriminating NCPF from CLD using McNemar test (p = 0.01). The SSM/LSM ratio is an excellent tool in differentiating NCPF from CLD.

Brief alcohol interventions are underutilized in persons with nonalcohol-associated chronic liver diseases.

Brief alcohol interventions use patient-provider communication to promote alcohol cessation. We characterized the receipt of this intervention in chronic liver disease (CLD). We surveyed patients with CLD for weekly drinking patterns and examined associations with patient-provider communication receipt. Among 840 participants, 82.1% and 56.5% reported ≥1 standard drink weekly and excessive alcohol consumption, respectively. Patient-provider communication was lower in noncirrhotic (adjusted odds ratio:0.34, 95% CI: 0.22-0.54) and nonalcohol-associated CLD (adjusted odds ratio: 0.22, 95% CI: 0.15-0.34) among individuals drinking ≥1 standard drink weekly, and similarly in noncirrhotic CLD (adjusted odds ratio: 0.45, 95% CI: 0.21-0.95) among those with excessive drinking. Brief alcohol interventions are underutilized in noncirrhotic and nonalcohol-associated CLD.

4D Flow MRI of Portal Vein Hemodynamics in Healthy Volunteers and Patients with Chronic Liver Disease.

To identify age-matched healthy volunteers, non-cirrhotic chronic liver disease (CLD) and cirrhotic patients based on portal hemodynamic parameters using 4D flow MRI. A total of 10 age-matched healthy volunteers and 69 CLD patients were enrolled and underwent 4D flow MRI prospectively. 4D flow MR images were processed by an MD in biomedical engineering working on the GTFlow platform. Portal hemodynamic parameters include net flow (mL/cycle), flow volume per second through the lumen (mL/sec), average flow velocity (cm/sec), and maximum flow velocity (cm/sec). The difference in portal hemodynamic parameters of 4D flow MRI was compared among healthy volunteers, non-cirrhotic CLD patients and patients with cirrhosis by one-way ANOVA or Kruskal-Wallis nonparametric test and post hoc tests. 10 CLD patients without cirrhosis and 56 patients with cirrhosis were eventually included, along with 10 healthy volunteers who were divided into three groups. 3 patients with cirrhosis whose image quality did not meet the requirements were excluded. There were no significant differences in portal hemodynamic parameters among the three groups except portal average velocity (P > 0.05). There was no statistical difference in all portal hemodynamic parameters of 4D flow MRI between healthy volunteers and patients with cirrhosis (P > 0.05). There were significant differences in portal average velocity between non-cirrhotic CLD patients, healthy volunteers and patients with cirrhosis, respectively (11.44±3.93 vs 8.10±2.66, P=0.013; 11.44±3.93 vs 8.60±2.22, P=0.007). Portal average velocity obtained by 4D flow MRI can be an auxiliary means to identify cirrhosis in patients with CLD.

The mortality of hospitalized patients with COVID-19 and non-cirrhotic chronic liver disease: a retrospective multi-center study

Background Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19. Methods This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19. Results Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) [1.70–305.38], p = 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI [1.12–100.31], p = 0.039), PT-INR (OR: 19.81, 95% CI [1.31–299.49], p = 0.031), hs-CRP (OR: 1.02, 95% CI [1.01–1.02], p = 0.001), albumin level (OR: 0.08, 95% CI [0.02–0.39], p = 0.002), and use of vasopressors (OR: 4.98, 95% CI [1.27–19.46], p = 0.021) were associated with the mortality. Conclusion The ALBI grade 3 and FIB-4 index ≥ 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PT-INR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission.

Statins Are Associated With a Decreased Risk of Severe Liver Disease in Individuals With Noncirrhotic Chronic Liver Disease

Little is known about the potential impact of statins on the progression of noncirrhotic chronic liver diseases (CLDs) to severe liver disease. Using liver histopathology data in a nationwide Swedish cohort, we identified 3862 noncirrhotic individuals with CLD and statin exposure, defined as a statin prescription filled for 30 or more cumulative defined daily doses. Statin users were matched to 3862 (statin) nonusers with CLD through direct 1:1 matching followed by propensity score matching. Cox regression was used to estimate hazard ratios (HRs) for the primary outcome of incident severe liver disease (a composite of cirrhosis, hepatocellular carcinoma, and liver transplantation/liver-related mortality). A total of 45.3% of CLD patients had nonalcoholic fatty liver disease, 21.9% had alcohol-related liver disease, 17.7% had viral hepatitis, and 15.1% had autoimmune hepatitis. During follow-up evaluation, 234 (6.1%) statin users vs 276 (7.1%) nonusers developed severe liver disease. Statin use was associated with a decreased risk of developing severe liver disease (HR, 0.60; 95% CI, 0.48-0.74). Statistically significantly lower rates of severe liver disease were seen in alcohol-related liver disease (HR, 0.30; 95% CI, 0.19-0.49) and in nonalcoholic fatty liver disease (HR, 0.68; 95% CI, 0.45-1.00), but not in viral hepatitis (HR, 0.76; 95% CI, 0.51-1.14) or autoimmune hepatitis (HR, 0.88; 95% CI, 0.48-1.58). Statin use had a protective association in both prefibrosis and fibrosis stages at diagnosis. Statin use was associated with lower rates of progression to cirrhosis (HR, 0.62; 95% CI, 0.49-0.78), hepatocellular carcinoma (HR, 0.44; 95% CI, 0.27-0.71), and liver-related mortality (HR, 0.55; 95% CI, 0.36-0.82). Among individuals with noncirrhotic CLD, incident statin use was linked to lower rates of severe liver disease, suggesting a potential disease-modifying role.

Safety and Immunogenicity of Anti-SARS-CoV-2 Booster Dose in Patients with Chronic Liver Disease

The low response to vaccines is a well-known problem in cirrhosis. We evaluated the safety and immunogenicity of booster doses in patients with chronic liver disease (CLD), comparing the humoral response in cirrhotic vs. non-cirrhotic patients, and the impact of different factors on immune response. From September 2021 to April 2022, outpatients with CLD who completed the primary vaccination course and the booster dose against SARS-CoV-2 were enrolled. Blood samples were collected after second and third doses for detecting anti-spike protein IgG. We enrolled 340 patients; among them, 91 subjects were cirrhotic. After primary vaccination course, 60 (17.6%) patients did not develop a positive antibody titer, without significant differences between cirrhotic and non-cirrhotic patients (p = 0.076); most of them (88.3%) developed it after booster dose. At multivariable analysis, factors associated with higher humoral response after booster dose were only porto-sinusoidal vascular disorder (p = 0.007) as an etiology of CLD and the use of the mRNA-1273 vaccine (p = 0.001). In conclusion, in patients with CLD, a booster dose against SARS-CoV-2 induces an excellent immunogenicity and leads to an adequate antibody response. Cirrhosis is not associated with a worse humoral response, compared to patients with non-cirrhotic CLD.

Differential Effects of COVID-19 Hospitalization on the Trajectory of Liver Disease Progression.

Patients with chronic liver disease (CLD) were significantly affected by COVID-19. Despite evidence of acute hepatic injury and increased mortality, the long-term effects of COVID-19 hospitalization on the natural history of CLD patients are unknown. The Massachusetts General Hospital COVID-19 registry was used to obtain a cohort of CLD patients hospitalized between March 8 and June 3, 2020. The Partners Research Patient Data Registry was used to develop a matched CLD patient control list without COVID-19. Fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS), and model for end-stage liver disease/Na (MELD-Na) scores were calculated pre-, day of, and 1-year post-discharge from admission. Unpaired t-test was used to compare continuous variables. Fifty-two COVID-19 patients and 92 control patients with CLD were included. Patients with non-cirrhotic CLD who were hospitalized for COVID-19 had an acute rise in FIB-4 on admission with subsequent improvement on one-year follow-up demonstrating no difference in progression of liver disease compared to the controls (P= .87, confidence interval [CI]-0.088 to 0.048). Similar trends were observed in nonalcoholic fatty liver disease patients using NFS (P= .48, CI-0.016 to 0.023). In contrast, patients with cirrhosis experienced rise in MELD-Na postadmission compared to the control cirrhosis group (0.35 vs-0.076/month; P= .04, CI-0.827 to-0.025), suggesting a potential for long-term consequences of COVID-19. Non-cirrhotic CLD patients who survive COVID-19 hospitalization do not appear to have change in FIB-4, NFS scores at one year. However, patients with cirrhosis exhibit increasing MELD-Na one-year post-COVID suggesting a differential effect of acute COVID-19 on the trajectory of established cirrhosis.

Deficient Immune Response following SARS-CoV-2 Vaccination in Patients with Hepatobiliary Carcinoma: A Forgotten, Vulnerable Group of Patients

Introduction: Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment. Methods: In this prospective, longitudinal study, 101 patients were included, of whom 59 were patients with HBC under anticancer treatment. A cohort of patients with a past medical history of gastrointestinal cancer, of whom 28.6% had HBC without detectable active tumor disease having been off therapy for at least 12 months, served as control. Levels of SARS-CoV-2 anti-spike IgG, surrogate neutralization antibodies (sNABs), and cellular immune responses were compared. In uni- and multivariable subgroup analyses, risk factors for impaired immunogenicity were regarded. Data on rates and clinical courses of SARS-CoV-2 infections were documented. Results: In patients with HBC under active treatment, levels of SARS-CoV-2 anti-spike IgG were significantly lower (2.55 log10 BAU/mL; 95% CI: 2.33–2.76; p < 0.01) than in patients in follow-up care (3.02 log10 BAU/mL; 95% CI: 2.80–3.25) 4 weeks after two vaccinations. Antibody levels decreased over time, and differences between the groups diminished. However, titers of SARS-CoV-2 sNAB were for a longer time significantly lower in patients with HBC under treatment (64.19%; 95% CI: 55.90–72.48; p < 0.01) than in patients in follow-up care (84.13%; 95% CI: 76.95–91.31). Underlying CLD and/or liver cirrhosis Child-Pugh A or B (less than 8 points) did not seem to further impair immunogenicity. Conversely, chemotherapy and additional immunosuppression were found to significantly reduce antibody levels. After a third booster vaccination for SARS-CoV-2, levels of total and neutralization antibodies were equalized between the groups. Moreover, cellular response rates were balanced. Clinically, infection rates with SARS-CoV-2 were low, and no severe courses were observed. Conclusion: Patients with active HBC showed significantly impaired immune response rates to basic vaccinations for SARS-CoV-2, especially under chemotherapy, independent of underlying cirrhotic or non-cirrhotic CLD. Although booster vaccinations balanced differences, waning immunity was observed over time and should be monitored for further recommendations. Our data help clinicians decide on individual additional booster vaccinations and/or passive immunization or antiviral treatment in patients with HBC getting infected with SARS-CoV-2.

The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis.

Systemic inflammatory responses are common in patients with chronic severe hepatitis (CSH) and increase their risk of mortality. Knowledge regarding the impact of the systemic inflammatory response on short-term outcomes in noncirrhotic CSH patients is limited. We collected data from two prospective, multicenter cohorts from the CATCH-LIFE non-cirrhotic cohort. Cox regression was used to explore the association between systemic inflammation markers and 90-day liver transplant (LT)-free mortality. Generalized additive model (GAM) was used to illustrate the quantitative curve relationship between the neutrophil-to-lymphocyte ratio (NLR) and 90-day LT-free mortality. Kaplan-Meier methods were used to estimate the 90-year LT-free survival rates. The prevalence of CSH in the CATCH-LIFE study was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively. Noninfected patients accounted for 75% of CSH patients, and the NLR was independently associated with 90-day LT-free mortality. Quantitative analysis of the association between the NLR and 90-day LT-free mortality showed that an NLR of 2.9 may represent the starting point for disease deterioration in CSH patients without infection. This study identified the NLR as an independent risk factor for 90-day LT-free mortality in noncirrhotic CLD patients. The NLR can better indicate the systemic inflammatory response in noninfected CSH patients. An NLR of 2.9 may be the cutoff for disease aggravation onset in CSH patients without infection.

Chronic liver disease and cirrhosis increase morbidity in geriatric patients treated surgically for hip fractures: analysis of the US Nationwide Inpatient Sample

BackgroundThis study aimed to evaluate the impact of chronic liver disease and cirrhosis on inpatient outcomes of geriatric hip fracture surgery.Materials and methodsUsing population-based retrospective study design, this study extracted data from the US Nationwide Inpatient Sample (NIS) database 2005–2014, identifying patients aged ≥ 65 years undergoing hip fracture repair. Main outcomes were in-hospital mortality, any/specific complications, non-routine discharge, extended length of stay (LOS) and hospital costs. Associations between cirrhosis, non-cirrhotic chronic liver disease and outcomes were determined using regression analysis.ResultsData of 347,363 hip fracture patients included 344,035 without liver disease, 1257 with non-cirrhotic chronic liver disease and 2,071 with cirrhosis. After adjustments, non-cirrhotic chronic liver disease was significantly associated with non-routine discharge (OR: 1.247, 95% CI: 1.038–1.498), acute kidney injury (OR: 1.266, 95% CI: 1.039–1.541), extended LOS (OR: 1.285, 95% CI: 1.122–1.473) and hospital costs (beta: 9173.42, 95% CI: 6925.9–11,420.95) compared to no liver disease; while cirrhosis was significantly associated with higher risk of in-hospital mortality (OR: 2.325, 95% CI: 1.849–2.922), any complication (OR: 1.295, 95% CI: 1.143–1.467), acute kidney injury (OR: 1.242, 95% CI: 1.177–1.433), non-routine discharge (OR: 1.650, 95% CI: 1.412–1.928), extended LOS (OR: 1.405, 95% CI: 1.263–1.562) and hospital costs (beta: 6680.24, 95% CI: 4921.53–8438.95) compared to no liver disease.ConclusionIn geriatric hip fracture patients undergoing surgical repair, non-cirrhotic chronic liver disease and cirrhosis independently predict non-routine discharge, acute kidney injury, prolonged LOS and greater hospital costs, and cirrhosis is also significantly associated with greater risk of any complication and in-hospital mortality.

Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions.

Chronic liver disease (CLD) and its complications constitute a significant cause of mortality and morbidity worldwide. Most deaths are secondary to the decompensation of cirrhosis and evolution of portal hypertension (PHTN). Since disease progression reversal is hardly attainable after decompensated cirrhosis develops, it is essential to intervene early with a therapeutic agent or regimen that could prevent or slow disease evolution. Thus far, there has been no agreed-upon medication to help in the fight against the development of cirrhosis or its decompensation. While early data depicted statins as harmful agents for the liver, current evidence from preclinical and clinical studies suggests that they might have positive impact on CLD. Low-quality evidence supports the fact that statins reduce mortality in CLD. Moderate-quality evidence suggests that statins reduce the risk of hepatic decompensation, variceal bleeding, and mortality, especially among patients with compensated cirrhosis. Combining this data with the long track-record of safety and tolerability of statins and their potential benefits in hepatocellular carcinoma (HCC) risk reduction, hepatologists might soon rely on statins to achieve better outcomes in their CLD and cirrhotic patients without significant additional costs. This review describes the rationale behind the use of statins in patients with CLD and cirrhosis. It sheds light on the current preclinical and clinical studies that reflect beneficial effects of the use of different types and doses of statins in the treatment of patients with different types and stages of CLD and cirrhosis. It also emphasizes the need for designing and developing additional large prospective interventional randomized control trials (RCTs) to better evaluate the association between statin exposure and the risk of fibrosis progression and development of cirrhosis in patients with non-cirrhotic CLDs, the risk of progression of PHTN in patients with cirrhosis, and the mortality rates in patients with cirrhotic or non-cirrhotic CLDs.

Acute hepatitis E virus superinfection increases mortality in patients with cirrhosis

BackgroundAlthough acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD).MethodsThis study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed.ResultsAmong the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate.ConclusionsOur findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Prognostic markers in patients with acute-on-chronic liver failure

Bckground and Aim: Acute-on-chronic liver failure (ACLF) defines an abrupt and life-threatening worsening of clinical conditions in patients with cirrhosis or chronic liver disease. APASL defines ACLF as an acute hepatic insult manifesting as jaundice (total bilirubin >5 mg/dl) and coagulopathy (INR of >1.5) complicated within 4 weeks by clinical ascites, encephalopathy or both in patients with compensated cirrhosis (diagnosed or undiagnosed) or non-cirrhotic chronic liver disease. Serum ferritin, an acute phase reactant is a known marker of hepatic necro-inflammation and has been studied to predict 1-year mortality in decompensated cirrhotics.

Animal Naming Test Is Associated With Poor Patient-Reported Outcomes and Frailty in People With and Without Cirrhosis: A Prospective Cohort Study.

INTRODUCTION:Cognitive dysfunction is a major driver of care complexity, poor patient-reported outcomes, and frailty for people with cirrhosis. The performance and clinical associations of the animal naming test (ANT) in the general population are unknown. We evaluated ANT performance in a representative sample of older Americans with and without chronic liver disease (CLD).METHODS:We analyzed 6,661 subjects enrolled in the 2010–2016 Health and Retirement Survey, a representative cohort of >30,000 US adults. Average age of participants was 75 years. We evaluated 3 subject subgroups: (i) without CLD, (ii) noncirrhosis CLD, and (iii) cirrhosis. We determined the association between the ANT (overall) and S-ANT1 <10 (adjusted for age and education) and health status, basic and instrumental activities of daily living, healthcare utilization (care hours received and hospitalizations), and frailty measures (hand grip and walk speed).RESULTS:Overall, 8.2% of the sample had noncirrhotic CLD and 1.3% had cirrhosis. CLD or cirrhosis was not independently associated with ANT. Poor ANT performance was associated with poor health status and frailty overall. An S-ANT <10 was associated with fair-poor self-reported health (odds ratio [OR] 1.37; 95% confidence interval [CI]: 1.20–1.56), care hours received (incidence rate ratio [IRR] 2.39; 95% CI: 1.79–3.19), and hospitalizations (IRR 1.14; 95% CI: 1.03–1.26). S-ANT <10 was also associated with activities of daily living disability (OR 1.31; 95% CI: 1.13–1.51), instrumental activities of daily living disability (OR 1.85; 95% CI: 1.59–2.14), weaker hand grip (IRR 0.94; 95% CI: 0.92–0.96), and time to walk 2.5 m (IRR 1.23; 95% CI: 1.17–1.29).DISCUSSION:ANT performance is not specific to CLD/cirrhosis but is associated with patient-reported outcomes and frailty in a nationally representative sample of elderly subjects with and without CLD.

Pregnancies With Cirrhosis Are Rising and Associated With Adverse Maternal and Perinatal Outcomes.

Cirrhosis incidence in pregnancies from outside the United States (US) is rising, although contemporary data including maternal and perinatal outcomes within the United States are lacking. Using discharge data from the racially diverse US National Inpatient Sample, temporal trends of cirrhosis in pregnancies were compared with noncirrhotic chronic liver disease (CLD) or no CLD. Outcomes included preterm birth, postpartum hemorrhage, hypertensive complications (preeclampsia, eclampsia, and/or hemolysis, elevated liver enzymes, and low platelets syndrome), and maternal or fetal death. Logistic regression was adjusted for age, race, multiple gestation, insurance status, and prepregnancy metabolic comorbidities. Among 18,573,000 deliveries from 2012 to 2016, 895 had cirrhosis, 119,875 had noncirrhotic CLD, and 18,452,230 had no CLD. Pregnancies with cirrhosis increased from 2.5/100,000 in 2007 to 6.5/100,000 in 2016 (P = 0.01). On adjusted analysis, cirrhosis was associated with hypertensive complications (vs no CLD, OR 4.9, 95% confidence intervals [CI] 3.3-7.4; vs noncirrhotic CLD, OR 4.4, 95% CI 3.0-6.7), postpartum hemorrhage (vs no CLD, OR 2.8, 95% CI 1.6-4.8; vs noncirrhotic CLD, OR 2.0, 95% CI 1.2-3.5), and preterm birth (vs no CLD, OR 3.1, 95% CI 1.9-4.9; vs noncirrhotic CLD, OR 2.0, 95% CI 1.3-3.3, P ≤ 0.01). Cirrhosis was statistically associated with maternal mortality, although rarely occurred (≤ 1%). In this racially diverse, US population-based study, pregnancies with cirrhosis more than doubled over the past decade. Cirrhosis conferred an increased risk of several adverse events, although maternal and perinatal mortality was uncommon. These data underscore the need for reproductive counseling and multidisciplinary pregnancy management in young women with cirrhosis.

Safety and Immunogenicity of SARS-CoV-2 Vaccines in Patients With Chronic Liver Diseases (CHESS-NMCID 2101): A Multicenter Study

Background & AimsWe aimed to assess the safety and immunogenicity of inactivated whole-virion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver diseases (CLD) in this study.MethodsThis was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose.ResultsA total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (n = 36; 8.2%) was the most frequently reported adverse event. Three participants had grade 3 aminopherase elevation (defined as alanine aminopherase >5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only 1 of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in the noncirrhotic CLD group, 78.9% in the compensated cirrhotic group, 76.7% in the decompensated cirrhotic group (P = .894 among CLD subgroups), and 90.3% in healthy controls (P = .008 vs CLD group).ConclusionInactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunologic response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in noncirrhotic CLD, compensated cirrhosis, and decompensated cirrhosis.

Role of Ultrasound and Transient Elastography in Diagnosis of Occult Cirrhosis in Chronic Liver Disease

Background: Hepatic cirrhosis represents the most advanced stage of any chronic liver disease characterized by progressive fibrosis. Complications including decompensation, spontaneous bacterial peritonitis, variceal bleeding, and hepatocellular carcinoma, carry significant morbidity and mortality. Early identification of patients with cirrhosis is of paramount importance to initiate surveillance protocols for prevention, early diagnosis, and specific therapies for such devastating complications. Objective: To investigate prevalence of preclinical cirrhosis diagnosed by transient elastography (TE) that we defined as occult cirrhosis (OC) and to evaluate the pattern of surveillance that patients with OC received in current clinical practice. Patients and methods: Our study included 60 chronic liver disease patients recruited from National Hepatology and Tropical Medicine Research Institute (NHTMRI) outpatient clinics to assess prevalence of occult cirrhosis among patients who have not any clinical or definite sonographic signs of liver cirrhosis, the study was divided into two groups: 1) Occult cirrhosis, defined as TE ≥13kPa and F4 on METAVIR scoring system. 2) non-cirrhotic chronic liver disease (CLD) (TE<13kPa). We found that the prevalence of OC is considerable, representing 15% of all CLD patients. This proportion suggests up to 1 in 7 individuals with CLD may have their OC missed. Results: Concerning the etiology of the chronic liver disease in our study, among the occult cirrhosis group there were 8 patients diagnosed as hepatitis C virus positive representing (89%) and one patient diagnosed as hepatitis B virus positive representing (11%) and among the non-cirrhotic group there were 42 patients diagnosed as hepatitis C virus positive representing (82%) and 4 patients diagnosed as hepatitis B virus positive representing (8%) and 5 patients diagnosed as non-alcoholic fatty liver disease (NAFLD) representing (10%). In our study among the occult cirrhosis group there were 5 male patients (55%) and 4 females (45%) with their age ranged between 33-55 years with the mean age 44 years and among the non-cirrhotic group there were 32 male patients (62.7%) and 19 female patients (37.3%) their age ranged between 19-58 years with the mean age 38.5 years. Conclusion: This study suggests that occult cirrhosis is a frequent finding. Clinicians should be aware that the absence of definite sonographic signs cannot rule out the possibility of compensated cirrhosis in its preclinical stage. Patients with occult cirrhosis can exhibit rapid development of hepatocellular carcinoma, variceal bleeding, and ascites.

Deoxycholic Acid Upregulates Serum Golgi Protein 73 through Activating NF-κB Pathway and Destroying Golgi Structure in Liver Disease.

Golgi protein 73 (GP73) is upregulated in a variety of liver diseases, yet the detailed mechanism is poorly characterized. We analyzed GP73 in a retrospective cohort including 4211 patients with chronic liver disease (CLD) or hepatocellular carcinoma (HCC). The effect of deoxycholic acid (DCA) and nuclear factor-kappa B (NF-κB) on expression and release of GP73 in Huh-7 and SMMC7721 cells were studied. A mouse study was used to confirm our findings in vivo. A positive correlation was found between serum GP73 and total bile acid (TBA) in cirrhotic patients (r = 0.540, p < 0.001), higher than that in non-cirrhotic CLD (r = 0.318, p < 0.001) and HCC (r = 0.353, p < 0.001) patients. In Huh-7 and SMMC7721 cells, DCA upregulated the expression and release of GP73 in a dose- and time-dependent manner. After overexpressing NF-κB p65, the promoter activity, GP73 messenger RNA (mRNA) level, and supernatant GP73 level were increased. The promotion effect of DCA on GP73 release was attenuated after inhibiting the NF-κB pathway. Mutating the binding sites of NF-κB in the sequence of the GP73 promoter led to a declined promoting effect of DCA on GP73. The upregulation role of DCA in GP73 expression through the NF-κB pathway was confirmed in vivo. In addition, exposure to DCA caused disassembly of Golgi apparatus. In summary, DCA upregulates the expression and release of GP73 via activating the NF-κB pathway and destroying the Golgi structure.

Poor Outcomes of Acute Hepatitis E in Patients With Cirrhotic Liver Diseases Regardless of Etiology.

Background: Chronic liver diseases (CLDs) have been documented to exacerbate clinical outcomes of acute hepatitis E (AHE). This study aimed to uncover the role of etiology and status of CLD in the adverse outcomes of AHE. We found that superinfection with hepatitis E virus (HEV) in patients with cirrhotic CLD can cause a worsen outcome, leading to exacerbation of AHE, compared with HEV-infected patients without CLD or with noncirrhotic CLD. Additional analysis revealed that the etiology of CLD is not associated with outcomes of AHE patients. These finding suggests that the overall liver status plays a predominant role in determining the outcomes of AHE.

Non-Cirrhotic Liver is Associated with Poor Prognosis of Hepatocellular Carcinoma: A Literature Review.

Primary hepatocellular carcinoma (HCC) is the fifth most frequently reported malignancy, and it is also the second most common cause of cancer-related deaths worldwide. Although most HCC cases have been reported to develop from cirrhosis, accumulating data suggest that HCC is also closely related to non-cirrhotic chronic liver disease. Traditionally, HCC was thought to develop mostly from cirrhosis; however, an increasing number of reports have found that HCC can develop directly from inflammation without cirrhosis. The incidence of HCC in non-cirrhotic liver (HCC-NCL) is high, especially in developed countries. Studies have found that the most common cause of HCC-NCL is neglected fatty liver disease. This type of HCC has unique clinical characteristics and is closely related to metabolic disorders. Unfortunately, the prevention of HCC-NCL has not received enough attention worldwide, and there is also a lack of specific screening methods and clinical guidelines. This article mainly reviews the etiology, incidence, clinical characteristics, and screening markers of HCC-NCL to improve the understanding and prevention of this disease.