Etiology Of Chronic Liver Disease Research Articles

Different Regimens of Vitamin D in treatment of children with chronic liver disease

Abstract Background Vitamin D is a steroid based hormone that has crucial role in calcium metabolism and bone homeostasis and potential role in fibrosis including liver. Patients with chronic liver disease has tendency for vitamin D deficiency with possible sequalae including hepatic osteodystrophy. Safe and effective regime of vitamin D that can be used in children with chronic liver disease is still not well established. Moreover, the potentiality of reversing fibrosis process or halting it by correction of vitamin D is still not well studied. Aim of work The primary aim of the study is to assess the efficacy and safety of vitamin D regime using two different mode of administration. The secondary aim is to assess the possible antifibrotic effect of vitamin D therapy by assessment of fibroscan. Methodology Twenty four children with different etiologies of chronic liver disease but age and sex matched as well as anthropometric measures are enrolled in the study. They were distributed randomly among the two arms of the study and followed up for 6 months using different laboratory and imaging variables. The two regimes were group A who received intramuscular stoss dose once (200.000 IU) vitamin D therapy while group B received oral vitamin D therapy with dose 50.000 IU for four weeks. All children received maintenance vitamin D (600 IU) and Ca doses thereafter for the whole follow up period. All patients were subjected to complete history taking, complete clinical examination including abdominal examination, signs of liver decompensation and signs of vitamin D deficiency. As regard laboratory investigations done were CBC, liver function tests, serum calcium and phosphorous. Serum vitamin D level and fibroscan were also done at the beginning and the end. Results There were significant improvement of vitamin D level in both arms with no development of toxic s/o of vitamin D toxicity with p-value of < 0.001 and 0.000 respectively in group A and B. The difference of improvements between both arms were not significant display the equal efficacy of both regimes (P = 0.885). There were no significant improvement of fibroscan parameters following vitamin D treatment in either group A or B with p-value 0.637 and 0.931 respectively. Conclusion Stoss and oral vitamin D regimes suggested in the study are both equally effective and safe in the treatment of vitamin D deficiency among children with chronic liver disease. Despite no proof of antifibrotic effect upon vitamin D correction, further study is required to evaluate this issue.

Statins in Chronic Liver Disease: Review of the Literature and Future Role.

Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid-lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, antiproliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and nonviral etiologies of CLD and hepatocellular carcinoma (HCC), and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

Quantitative measurements of M2BPGi depend on liver fibrosis and inflammation.

The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology. We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation. In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001). The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage.

Differences in branched-chain amino acid to tyrosine ratio (BTR) among etiologies of chronic liver disease progression compared to healthy adults.

The branched-chain amino acids (BCAAs) to tyrosine (Tyr) ratio (BTR) test is used to evaluate the progression of chronic liver disease (CLD). However, the differences across sex, age, body mass index (BMI) and etiologies are still unclear. We retrospectively reviewed data from 2,529 CLD cases with free amino acids (FAAs) in peripheral blood from four hospitals and 16,421 general adults with FAAs data from a biobank database. In total, 1,326 patients with CLD (covering seven etiologies) and 8,086 healthy controls (HCs) were analyzed after exclusion criteria. We investigated the change of BTR in HCs by sex, age and BMI and then compared these to patients divided by modified ALBI (mALBI) grade after propensity score matching. BTR is significantly higher in males than females regardless of age or BMI and decreases with aging in HCs. In 20 types of FAAs, 7 FAAs including BCAAs were significantly decreased, and 11 FAAs including Tyr were significantly increased by mALBI grade in total CLD. The decreasing timings of BTR were at mALBI grade 2b in all CLD etiologies compared to HCs, however in chronic hepatitis C (CHC), chronic hepatitis B (CHB) and alcoholic liver disease (ALD), BTR started to decrease at 2a. There was a positive correlation between BCAAs and albumin among parameters in BTR and mALBI. The correlation coefficients in PBC, ALD and MASLD were higher than those of other etiologies. BTR varies by sex and age even among healthy adults, and decreasing process and timing of BTR during disease progression is different among CLD etiologies.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

The Role of Hypoxia-Inducible Factor 1 Alpha in Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is associated with increased mortality. Specific therapy options are limited. Hypoxia-inducible factor 1 alpha (HIF-1α) has been linked to the pathogenesis of chronic liver disease (CLD), but the role of HIF-1α in ACLF is poorly understood. In the current study, different etiologies of CLD and precipitating events triggering ACLF were used in four rodent models. HIF-1α expression and the intracellular pathway of HIF-1α induction were investigated using real-time quantitative PCR. The results were verified by Western blotting and immunohistochemistry for extrahepatic HIF-1α expression using transcriptome analysis. Exploratory immunohistochemical staining was performed to assess HIF-1α in human liver tissue. Intrahepatic HIF-1α expression was significantly increased in all animals with ACLF, regardless of the underlying etiology of CLD or the precipitating event. The induction of HIF-1α was accompanied by the increased mRNA expression of NFkB1 and STAT3 and resulted in a marked elevation of mRNA levels of its downstream genes. Extrahepatic HIF-1α expression was not elevated. In human liver tissue samples, HIF-1α expression was elevated in CLD and ACLF. Increased intrahepatic HIF-1α expression seems to play an important role in the pathogenesis of ACLF, and future studies are pending to investigate the role of therapeutic HIF inhibitors in ACLF.

The changing epidemiology of adult liver transplantation in the United States in 2013-2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States. The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant. There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes. Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC.

MELD-Na score may underestimate disease severity and risk of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)

Portal hypertension often precedes the development of advanced fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) and may accelerate disease progression to cirrhosis. We aimed to evaluate whether prioritization tools accurately predict survival in patients with MASLD and clinically significant portal hypertension (CSPH). We retrospectively identified patients diagnosed with esophageal or gastric varices (EGV). Laboratory results, endoscopy reports and outcomes of patients with MASLD were compared to patients with advanced stage chronic liver disease (CLD) of other etiologies. During the study period 326 patients were diagnosed with EGV. 88 (26.9%) had MASLD, 113 (34.6%) viral hepatitis (VH), 63 (19.3%) alcoholic liver disease (ALD) and 62 (19%) both VH and ALD (VHALD). EGV bleeding events were significantly more frequent in patients with MASLD (36.3%), compared to VH (28.3%), ALD (30.1%) and VHALD (25.8%), respectively (p < 0.01). Mean Model for End-Stage Liver Disease (MELD)-Na score surrounding 1 year of first event of EGV bleeding was significantly lower in MASLD patients compared to all other etiologies (p = 0.02). At a MELD-Na score of 11–20, cumulative survival rate was significantly lower in MASLD patients compared to all other etiologies (log rank p < 0.01). MASLD patients present with EGV bleeding at lower MELD-Na scores compared to other etiologies of CLD. MELD-Na score may therefore underestimate disease severity and risk of death in patients with MASLD and CSPH.

Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score

BackgroundDiagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). MethodsA multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. ResultsAmong 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. ConclusionsDespite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Serum uric acid level in chronic liver disease and its correlation with Child-Pugh score in a tertiary care hospital from South India.

Chronic liver disease (CLD) is one of the important causes of morbidity and mortality in our country, and since the damage to the liver is irreversible, we have to look for many severity markers or predictors for the prognosis of the patient. In this study, we have tried to correlate the level of serum uric acid (UA) with the severity of CLD presented as a Child-Pugh score. A cross-sectional observational study was conducted at Vijayanagar Institute of Medical Science (VIMS), Ballari, Karnataka, from October 2015 to June 2017 in the Department of General Medicine. Fifty patients diagnosed with CLD, aged between 18 and 65 years, of either gender, were enrolled in the study. Serum UA levels were measured, and liver function and coagulation parameters were assessed. A statistical analysis was performed to evaluate the association between serum UA levels, liver function test, and coagulation parameters. In our study, the mean serum UA level was 6.52 mg/dl and was raised in patients with CLD in correlation to its severity. Alcoholic liver disease (ALD) was the most common etiology for CLD (80%) followed by hepatitis B (Hep B) virus infection (12%) and hepatitis C (Hep C) virus infection (6%). Serum UA levels increased as the Child-Turcotte-Pugh (CTP) score increased. The mean UA level in CTP class C was 8.29 mg/dl. Various parameters such as serum aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, total bilirubin, international normalized ratio (INR), calcium, and albumin were significantly associated with serum UA levels in CLD patients. The correlation between rising blood UA levels and the Child-Pugh score shows that UA estimate may be a valid and affordable indicator for assessing the extent of liver cirrhosis in CLD.

The evolution of liver transplant program in Pakistan and the challenges ahead

Background and aimThe burden of Liver disease has significant implications on the healthcare infrastructure in Pakistan, with viral hepatitis being the leading etiology of end-stage liver disease. Liver transplant remains the only curative treatment option for end-stage liver disease. A decade ago, the liver transplant facility was almost non-existent for the Pakistani population, and the patients with end-stage liver disease had to travel overseas to receive liver transplantation. Gradually, during the last decade the country has progressed steeply and achieved various milestones in living donor liver transplantation. Various public and private sector hospitals are providing liver transplant services nationwide. The study aimed to describe the evolution and success of living donor liver transplant programs in Pakistan. We will also discuss the current practices involved in donor and recipient selection, factors related to non-existent deceased donor organ programs, and the introduction of innovative strategies to overcome the shortage of donor organ pools. MethodsWe retrospectively analyzed the data of the first 416 living donor liver transplants (LDLTs) performed at PKLI&RC from March 2019 to April 2023. The stepwise approach for the donor and recipient selection process is described in detail, along with the survival outcomes of LDLT at our center. ResultsAmong the 416 living donor liver transplants performed between March 2019 and April 2023. The Hepatitis C virus was the most common etiology (50.5 %) for chronic liver disease. Hepatocellular carcinoma (HCC) was present in 27.9 % of cases. Most donors were offspring of the recipients, with sons accounting for 23 % and daughters for 17.5 % of cases. Only a single (0.24 %) patient had a deceased donor transplant. The annual donor rejection rate was up to 68 % at our center. Nine SWAP transplants were performed to overcome the donor shortage. The Clavien Dindo classification system was used to grade the severity of complications after donor hepatectomy. No donor mortality (grade-5 complication) was observed in our cohort, whereas 1- and 3-year recipient survival rates were 89 % and 88 %, respectively. ConclusionHepatitis C virus remains the most common etiology of chronic liver disease requiring liver transplantation. The major pool of living donations was from first-degree relatives. There was no donor mortality with acceptable 1- and 3-year recipient's survival rates. Living donor liver transplantation is a feasible and safe strategy in regions where cadaveric liver transplant program is limited.

Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors. We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry. The assessed clinical outcomes were HCC development, liver transplantation, and death. Fine and Gray regression analysis stratified by centre was applied to determine the effects of individual covariates; the cumulative incidence of HCC was estimated using the competing risk method with death as a competing risk. A total of 1,428 patients diagnosed with AIH from 1980 to 2020 from 22 eligible centres across Europe and Canada were included, with a median follow-up of 11.1 years (interquartile range 5.2-15.9). Two hundred and ninety-three (20.5%) patients had cirrhosis at diagnosis. During follow-up, 24 patients developed HCC (1.7%), an incidence rate of 1.44 cases/1,000 patient-years; the cumulative incidence of HCC increased over time (0.6% at 5 years, 0.9% at 10 years, 2.7% at 20 years, and 6.6% at 30 years of follow-up). Patients who developed cirrhosis during follow-up had a significantly higher incidence of HCC. The cumulative incidence of HCC was 2.6%, 4.6%, 5.6% and 6.6% at 5, 10, 15, and 20 years after the development of cirrhosis, respectively. Obesity (hazard ratio [HR] 2.94, p=0.04), cirrhosis (HR 3.17, p=0.01), and AIH/PSC variant syndrome (HR 5.18, p=0.007) at baseline were independent risk factors for HCC development. HCC incidence in AIH is low even after cirrhosis development and is associated with risk factors including obesity, cirrhosis, and AIH/PSC variant syndrome. The risk of developing hepatocellular carcinoma (HCC) in individuals with autoimmune hepatitis (AIH) seems to be lower than for other aetiologies of chronic liver disease. Yet, solid data for this specific patient group remain elusive, given that most of the existing evidence comes from small, single-centre studies. In our study, we found that HCC incidence in patients with AIH is low even after the onset of cirrhosis. Additionally, factors such as advanced age, obesity, cirrhosis, alcohol consumption, and the presence of the AIH/PSC variant syndrome at the time of AIH diagnosis are linked to a higher risk of HCC. Based on these findings, there seems to be merit in adopting a specialized HCC monitoring programme for patients with AIH based on their individual risk factors.

Advanced Hepatocellular Carcinoma Patients with Poor Access to Systemic Therapy Treated with Definitive Stereotactic Body Radiation Therapy: A Single-Institution Experience in Latin America

The standard treatment for patients with advanced hepatocellular carcinoma (aHCC) is systemic therapy with or without stereotactic body radiation therapy (SBRT). We present our experience using SBRT as a definitive treatment for aHCC patients with poor access to systemic therapy. We performed a retrospective review of patients treated with SBRT at the largest institution in Santiago, Chile between June 2016 and September 2022. All patients were deemed unsuitable for another locoregional treatment by the tumor board. We registered demographic, clinical and treatment characteristics. Additionally, treatment response rates using mRECIST criteria, overall survival (OS), local control (LC) and treatment toxicity were reported. We performed a multivariate analysis of variables using Cox proportion hazard ratio for OS and logistic regression for LC. A total of 59 patients were included (41 males and 18 females; median age: 70 years [range: 38 - 85 years]), with a total of 63 treatment courses. Most common etiologies of chronic liver disease were nonalcoholic fatty liver disease (23%) and chronic alcohol consumption (20%). Most patients were classified as Child-Pugh Class A (80%). Barcelona Clinic Liver Cancer (BCLC) stage was 2%, 11%, 49% and 38% for stages 0, A, B and C, respectively, while macrovascular invasion was present in 10 (18%) of patients. Forty-six patients (73%) had been subjected to prior locoregional therapy and only 5 patients (8,5%) received systemic therapy after SBRT. Median tumor size was 7 cm. (range: 0.95 - 32 cm). Median radiation dose was 40 Gy (range: 26.5 - 50 Gy) in 5 fractions. Evaluation of radiological response was performed in 46 patients (79%), with complete response, partial response, stable disease and progressive disease in 41%, 43%, 7% and 9% of the cohort, respectively. With a median follow-up of 9 months (range: 0 - 58), 34 patients (58%) died with a median OS of 10.8 months (range: 0 - 28 months). At 12 months, OS was 65.2% (95% CI: 50.9 - 76.3) and at 24 months was 40.7% (95% CI: 26.2 - 54.6) In multivariate analysis tumor size (as a continuous variable) was the only significant variable for LC (OR 2.9 [CI 1.1 - 5.3; p 0.03]) and for OS (HR 3.4 [CI 1.3 - 6.7; p< 0.01]). Four patients developed grade 3 toxicity (3 thrombocytopenia and 1 duodenal ulcer) and only two treatments were suspended definitively. Despite systemic therapy is the standard treatment for aHCC, a minor proportion of patients received the standard of care. SBRT is safe, feasible and a well-tolerated treatment option for aHCC with good clinical outcomes. To our knowledge, this is the first cohort reported of patients with aHCC treated with SBRT in Latin America.

The Trends in Health Care Utilization and Costs Associated With Primary Liver Cancer: An Analysis of United States Hospitals Between 2016 and 2019.

Primary liver cancer (PLC) has placed an increasing economic and resource burden on the health care system of the United States. We attempted to quantify its epidemiology and associated costs using a national inpatient database. Hospital discharge and insurance claims data from the National Inpatient Sample were used to conduct this analysis. Patients diagnosed with PLC (hepatocellular carcinoma or cholangiocarcinoma) were included in the study population, which was then stratified using patient demographics, comorbidities, degree of cancer spread, liver disease complications, and other descriptors. Trends were analyzed via regression curves for each of these strata from the years 2016 to 2019, with special attention to patterns in hospitalization incidence, inpatient mortality rate, total costs, and average per-capita costs. The resulting curves were evaluated using goodness-of-fit statistics and P-values. Aggregate hospitalization incidence, inpatient mortality rates, and total costs were found to significantly increase throughout the study period (P=0.002, 0.002, and 0.02, respectively). Relative to their demographic counterparts, males, White Americans, and those older than 65 years of age contributed the largest proportions of total costs. These population segments also experienced significant increases in total expenditure (P=0.04, 0.03, and 0.02, respectively). Admissions deemed to have multiple comorbidities were associated with progressively higher total costs throughout the study period (P=0.01). Of the categorized underlying liver diseases, only admissions diagnosed with alcoholic liver disease or nonalcoholic fatty liver disease saw significantly increasing total costs (P=0.006 and 0.01), although hepatitis C was found to be the largest contributor to total expenses. From 2016 to 2019, total costs, admission incidence, and inpatient mortality rates associated with PLC hospitalization increased. Strata-specific findings may be reflective of demographic shifts in the PLC patient populations, as well as changes in underlying chronic liver disease etiologies.

The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.

An Approach to Investigations of Chronic Liver Disease.

Chronic liver disease (CLD) in children is more diverse compared to adults with respect to the etiology, progression and response to therapy. After history and clinical examination, the first step is to confirm the presence of CLD with basic blood investigations and ultrasonography. Markers of portal hypertension are splenomegaly, increased portal vein diameter, thrombocytopenia and presence of varices on endoscopy. The next step is to evaluate the etiology of CLD which will depend on the age of the child and needs targeted investigations as metabolic and inherited causes predominate in early childhood. CLD progression ought to be monitored regularly and several non-invasive markers are available but they have to be evaluated further in children. Since CLD progresses, complications have to be detected early not only to initiate appropriate treatment but also to prognosticate.

Investigation on the short‐term outcome and prognostic impact of predisposition, and precipitants in inpatients with chronic liver disease from Chinese AcuTe on CHronic LIver FailurE (CATCH‐LIFE) cohorts

AbstractAimThe study aimed to investigate the short‐term outcomes of hospitalized patients with chronic liver disease (CLDs) and assess the prognostic impact of predisposition and precipitants, which currently remains unclear.MethodsThe study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies (NCT02457637 and NCT03641872) conducted in highly endemic hepatitis B virus (HBV) areas. Competing risk analysis was used to evaluate the effect of predispositions, including the etiology and severity of CLDs and precipitants; on sequential 28, 90, and 365‐day liver transplantation (LT)‐free mortality.ResultsAmong all enrolled patients, 76.8% of adverse outcomes (including death and LT) within one year occurred within 90 days. Compared with alcoholic etiology, the association of HBV etiology with poorer outcomes was remarkably on the 28th day (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.07–3.06; p = 0.026); however, and diminished or became insignificant at 90 days and 365 days. Cirrhosis increased the adjusted risk for 365‐day (HR, 1.50; CI, 1.13–1.99; p = 0.004) LT‐free mortality when compared with noncirrhosis. In patients with cirrhosis, prior decompensation (PD) independently increased the adjusted risk of 365‐day LT‐free mortality by 1.25‐fold (p = 0.021); however, it did not increase the risk for 90‐day mortality. Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90‐day LT‐free mortality.ConclusionsThe 90‐day outcome should be considered a significant endpoint for evaluating the short‐term prognosis of hospitalized patients with CLD. Predisposing factors, other than etiology, mainly affected the delayed (365‐day) outcome. Timely effective therapy for CLD etiology, especially antiviral treatments for HBV, and post‐discharge long‐term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.

The Prevalence of Non-Alcoholic Fatty Liver Disease in Iranian Children and Adult Population: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is the world's most common etiology of chronic liver disease. In this systematic review and meta-analysis, we estimated the prevalence of NAFLD in the Iranian children and adult population. A comprehensive search of five international databases, including PubMed, ISI/WOS, ProQuest, Scopus, and Google Scholar, was done from inception to Nov 2022. Studies on NAFLD patients and their risk factors were selected for meta-analysis. The quality of the included studies was assessed by The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for cross-sectional, and cohort studies. The heterogeneity between studies was investigated using Cochran test and I2 statistics. Random and fixed effect models were used for heterogenic and non-heterogenic studies, respectively. We used Comprehensive Meta-Analysis version 3 for conducting meta-analysis. Twenty studies were finally included. The total prevalence of NAFLD in children, boys, and girls was 6.7% (95% CI: 0.02-0.18), 12.5% (95% CI: 0.04-0.29) and, 10.1% (95% CI: 0.04-0.21), respectively. The total prevalence of NAFLD in obese children, obese boys, and obese girls was 42% (95% CI: 0.18-0.69), 44% (95% CI: 0.13-0.80), and 33 % (95% CI: 0.13-0.62), respectively. The total prevalence of NAFLD in adults was 36.9% (95% CI: 0.31-0.42). The prevalence of NAFLD in men and women was 33.8% (95% CI: 0.27-0.41) and 29.9% (95% CI: 0.21-0.40), respectively. NAFLD prevalence in Iranian adults and obese children is considerable; however, data about the children population was insufficient.

Frequency of significant steatosis and compensated advanced chronic liver disease among adults with chronic liver disease.

With changes in the epidemiology and treatment of chronic liver disease (CLD), the impact of various etiologies of liver disease on steatosis and advanced fibrosis are uncertain. A retrospective study was conducted among liver disease patients of various etiologies undergoing transient elastography (TE) over a 9-year duration. Data for 2886 patients were analyzed and had the following demographics: The median age was 60 (IQR: 45-69) years, 51% were males, and ethnicity was predominantly Chinese (52.5%), followed by Malays (34%) and Indians (12.3%). The median CAP score was 272 (IQR: 219-319) dB/m and the median liver stiffness measurement (LSM) score was 6.5 (IQR: 4.9-9.7) kPa. Hepatic steatosis occurred across the spectrum of etiologies of CLD. Among patients with steatosis, the most common etiologies were nonalcoholic fatty liver disease (NAFLD) at 62% and chronic hepatitis B (CHB) at 26.3%. TE findings suggestive of cACLD (10.1-15kPa) and highly suggestive of cACLD (>15kPa) were observed in 11.3% and 12.4% of patients, respectively. NAFLD was found to be the most common etiology for cases with suggestive of cACLD (47.2%) and highly suggestive of cACLD (41.5%). Hepatic steatosis is common in CLD, regardless of etiology. Compared with other etiologies, NAFLD is now the leading cause of cACLD.

Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis.

Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD-1.6 (95 % CI:-2.66 to-0.54), p<0.01] and alcoholic liver disease (3 studies) [MD-0.84 (95 % CI:-1.6 to-0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD-0.65 (95 % CI:-1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD-1.02 (CI:-1.59 to-0.45), p<0.01] vs. controls (CI: confidence interval). Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.