Etiology Of Chronic Liver Disease Research Articles

Ultrasound-guided percutaneous microwave ablation for metabolic-associated fatty liver disease-related hepatocellular carcinoma (HCC) versus hepatitis virus B-related HCC: a propensity score matching study

Objectives To compare the long-term outcomes of microwave ablation (MWA) for primary hepatocellular carcinoma (HCC) in patients with metabolic-associated fatty liver disease (MAFLD) with those infected by hepatitis virus B (HBV). Methods The clinical data of HCC patients under the treatment of MWA were analyzed retrospectively between 2010 and 2021 at Chinese PLA General Hospital. Patients were divided into MAFLD-HCC and HBV-HCC group according to the chronic liver disease etiology. The propensity score matching (PSM) was performed to reduce the interference of confounders. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), cancer-specific survival (CSS) and intrahepatic distant recurrence (IDR). Results A total of 648 patients (age range, 18–91 years) with 1019 lesions were enrolled including 601 with HBV-HCC and 47 with MAFLD-HCC. After a variable ratio of 1:n ≤ 4 PSM, 100 patients were included in the HBV-HCC and 41 in the MAFLD-HCC group. No statistical differences in OS and CSS (p = 0.880 and p = 0.980, respectively) were observed between the two groups in the matched cohort, while MAFLD-HCC exhibited better RFS and lower IDR rates compared to HBV-HCC (p = 0.043 and p = 0.041, respectively). Additionally, MAFLD-HCC generated lower ascending range in the liver function indexes like ΔALT (46.7 vs. 98.5, p < 0.001), ΔTBIL (1.9 vs. 7.5, p = 0.001) and ΔAST (38.1 vs. 148.6, p < 0.001) than HBV-HCC after MWA. Conclusions MWA is an effective treatment for HCC patients with MAFLD. The recurrence prognosis of MAFLD-HCC was better than HBV-HCC and the degree of liver injury after MWA was lower.

Long-term Outcomes and Risk Modifiers of MASLD Between Lean and Non-Lean Populations.

One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD) - formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study's comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals' unique risks.

Redox Homeostasis and Non-Invasive Assessment of Significant Liver Fibrosis by Shear Wave Elastography.

Hepatic fibrosis with various origins can be estimated non-invasively by using certain biomarkers and imaging-based measurements. The aim of our study was to examine redox homeostasis biomarkers and liver stiffness measurements for the assessment of significant liver fibrosis in different etiologies of chronic liver diseases. A cohort study consisting of 88 chronic liver disease patients of both sexes (age 49.1 ± 14.7 years) was performed. Cytokine profiles as well as redox homeostasis characteristics were determined. Liver fibrosis stages were assessed with shear wave elastography. The plasma levels of four cytokines showed no significant alteration between the four fibrotic stages; however, higher values were measured in the F2-4 stages. Free sulfhydryl group concentration, the marker of redox homeostasis, was lower in significant fibrosis (F0-F1: 0.36 ± 0.06 vs. F2-4: 0.29 ± 0.08 mmol/L, p < 0.05). Higher chemiluminescence values, as free radical-antioxidant parameters, were detected in advanced fibrosis stages in erythrocytes (F0-F1: 36.00 ± 37.13 vs. F2-4: 51.47 ± 44.34 RLU%). These data suggest that oxidative stress markers can predict significant fibrosis, with the aim of reducing the number of protocol liver biopsies in patients unlikely to have significant disease; however, their role in distinguishing between the certain fibrosis groups needs further studies.

The Role of Tripartite Motif Family Proteins in Chronic Liver Diseases: Molecular Mechanisms and Therapeutic Potential.

The worldwide impact of liver diseases is increasing steadily, with a consistent upswing evidenced in incidence and mortality rates. Chronic liver diseases (CLDs) refer to the liver function's progressive deterioration exceeding six months, which includes abnormal clotting factors, detoxification failure, and hepatic cholestasis. The most common etiologies of CLDs are mainly composed of chronic viral hepatitis, MAFLD/MASH, alcoholic liver disease, and genetic factors, which induce inflammation and harm to the liver, ultimately resulting in cirrhosis, the irreversible final stage of CLDs. The latest research has shown that tripartite motif family proteins (TRIMs) function as E3 ligases, which participate in the progression of CLDs by regulating gene and protein expression levels through post-translational modification. In this review, our objective is to clarify the molecular mechanisms and potential therapeutic targets of TRIMs in CLDs and provide insights for therapy guidelines and future research.

Frequency of Peptic Ulcer Disease in Patients with Chronic Liver Disease Presenting with Upper Gastrointestinal Bleeding

Background: Peptic ulcer disease (PUD) is a significant cause of morbidity and mortality worldwide, particularly in patients with chronic liver disease (CLD). The occurrence of upper gastrointestinal bleeding (UGIB) in CLD patients presents a serious complication, often requiring urgent medical intervention. Objective: The main objective of this study was to determine the frequency of peptic ulcer disease in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Methods: This retrospective observational study was conducted at Ayub Teaching Hospital, Abbottabad, from 2021 to 2023. Data were collected from 105 patients diagnosed with chronic liver disease who presented with symptoms of upper gastrointestinal bleeding. The diagnosis of CLD was confirmed through clinical evaluation, biochemical tests, imaging studies, and/or liver biopsy. Patients included were aged 18 years and above and presented with UGIB evidenced by hematemesis, melena, or both. Exclusion criteria were individuals with bleeding disorders unrelated to CLD and those who did not undergo endoscopic evaluation. Data collection involved demographic information, clinical history, duration and etiology of CLD, comorbid conditions, and UGIB presentation. Upper gastrointestinal endoscopy was performed on all patients to identify the source of bleeding. Statistical analysis was performed using SPSS version 25, with a p-value of less than 0.05 considered statistically significant. Results: The study included 105 patients, with a mean age of 55.3±3.27 years; 65 (61.9%) were male, and 40 (38.1%) were female. The etiologies of CLD were viral hepatitis (42.9%), alcoholic liver disease (28.6%), non-alcoholic fatty liver disease (19.0%), and other causes (9.5%). Clinical presentations of UGIB included hematemesis (66.7%), melena (23.8%), and both (9.5%). Endoscopic findings revealed that 35 patients (33.3%) had peptic ulcer disease, with 20 (57.1%) having duodenal ulcers and 15 (42.9%) having gastric ulcers. Other sources of UGIB included esophageal varices (38.1%), gastric varices (14.3%), erosive gastritis (9.5%), and malignancies (4.8%). Associated risk factors for PUD included NSAID use (42.9%), smoking (28.6%), and coexisting portal hypertension (71.4%). The mean size of ulcers was 10.2 mm. Endoscopic therapy was utilized in 71.4% of cases, with pharmacological treatment primarily including proton pump inhibitors (85.7%). Complications included rebleeding within 7 days (14.3%) and the need for surgical intervention (5.7%). The mean hospital stay was 7.8 days, and in-hospital mortality was observed in 8.6% of patients. Conclusion: Peptic ulcer disease represents a substantial yet manageable complication in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Prompt recognition and targeted therapeutic interventions are crucial for optimizing outcomes in this high-risk population.

Acute-on-chronic liver failure in metabolic dysfunction-associated fatty liver disease patients: a disease multiplier.

Acute-on-chronic liver failure (ACLF) is a syndrome of liver failure due to an acute hepatic insult leading to liver failure with or without extra-hepatic organ failure in a patient of chronic liver disease (CLD) with or without cirrhosis presenting for the first time. The definition is still with controversy; hence, homogeneity and clarity of the case is an unmet need. There is a paradigm shift noted as far as the etiology of CLD is concerned with rise in metabolic dysfunction-associated fatty liver disease (MAFLD) and ethanol as the dominant cause even in developing countries. MAFLD is the change in nomenclature from NAFLD to justify the metabolic derangement in these group of patients. The shift from an exclusion-based criteria to one that has evolved to a diagnosis that requires positive criteria has profound significance. Clearly there is a difference in terms of its prevalence, disease progression, and liver-related events, as well as management of metabolic risk factors and MAFLD itself which requires further understanding. In tandem with the global rise in MAFLD, the incidence of MAFLD-ACLF is increasing. Excessive alcohol consumption causes metabolic and toxic injury to the liver resulting in nearly similar pathway of fatty liver, hepatitis, and cirrhosis. The interaction of MAFLD as an additional underlying chronic liver injury in ACLF patients is complex due to the presence of metabolic risk factors that are unique to MAFLD. There is lack of clarity on how MAFLD affects the clinical course of ACLF due to scarcity of this specific data. This narrative review aims to understand the unique effects, consequences, and management of MAFLD as the chronic liver injury component in ACLF.

Profile of spontaneous bacterial peritonitis in non-alcoholic fatty liver disease cirrhosis

Background: Etiology of chronic liver disease (CLD) has an impact on the profile of spontaneous bacterial peritonitis (SBP) in terms of infection acquisition, resistance pattern, and treatment outcome. Aims and Objectives: This study aimed to study infection acquisition, antibiotic resistance pattern, and treatment outcome in patients with non-alcoholic fatty liver disease (NAFLD) cirrhosis with SBP. Materials and Methods: This observational prospective study was carried out in Government Medical College; Srinagar: over a period of 2 years from 2017 onward. We did analysis of patients with NAFLDs cirrhosis. We studied infection acquisition, antibiotic resistance pattern, and treatment outcome in this group of patients. Results: Over 2-year period, 246 patients were enrolled. The mean age of patients was 57.09±13.90 years. Hepatitis B virus and NAFLD were the major etiological contributors to the burden of CLD amounting to 51.20% in Kashmir. SBP was present in 33/57 (57.90%) of NAFLD cirrhosis patients. Child-Turcotte-Pugh Class C was 63.60%. Patients with culture-positive SBP (CP-SBP) were 45.45%. In patients of SBP with etiology other than NAFLD, CP-SBP was 61% whereas culture-negative SBP was 38.77%. Conclusion: In our region, NAFLD is one of the leading contributors to CLD. In this study, the trend toward worse treatment outcome and mortality in the patients with NAFLD SBP was observed.

The burden of steatotic liver disease

The steatotic liver disease is one of the most common etiologies of chronic liver diseases, especially in developed countries. It is in direct correlation with the prevalence of the metabolic syndrome and the western lifestyle. Thus, we aimed to study the impact of fatty liver disease globally, depending on geographic distribution, age, gender, and associated risk factors, using the searche engines PubMed and Google Scholar. It has been observed that steatotic liver disease is a globally prevalent disease, which is more common in men and post-menopausal women, suggesting the protective role of female sex hormones. Steatotic liver disease is also considered the hepatic manifestation of the metabolic syndrome, being frequently diagnosed among patients with type 2 diabetes and/or obesity. The increased incidence of the disease was also noted in children, overweight / obese adolescents. Steatotic liver disease is a burden both for the patient and society as a whole, requiring the need for screening and early diagnosis.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

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 &amp;lt; 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.