Extrahepatic Complications Research Articles

Clinical profile of Non Alcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus

NAFLD is also potentially contributing to an important burden of extra-hepatic chronic complications. For reasons that are not completely clear, NAFLD is more common in men than women and although precise estimates of incidence rates for NAFLD are uncertain (because of difficulties with establishing a precise diagnosis during sequential follow up), current incidence rates are approximately 20/10,000 person years, peaking in the sixth decade of life. Aim: To study the clinical profile of non alcoholic fatty liver disease in type 2 Diabetes Mellitus. Material and methods: A cross sectional study was carried out among 50 cases having type 2 DM were further evaluated for non alcoholic fatty liver disease under Medicine Department of tertiary health care center. Detailed clinical profile of the participants were studied. All data was collected and complied in Microsoft excel. All statistical analyses were performed by using IBM SPSS statistics Version 21.0 (SPSS Inc., Chicago, IL, USA) and openepi version 2.3.1. Results: Majority 79% were in age group >40 years. Mean age in years was 65.8 +11.26, male preponderance was seen. Mean HbA1C was 7.5+0.73, ranging from 5.1 to 12.5. majority 70% had HbA1C >6, 20% had between 5.7- 6 and 10% had <5.7. Mean SGOT was 66.3+ 76.6, mean SGPT was 44.6+46.8, mean ALP was 98.1+40.3.On USG finding majority 60% had grade 1, 30% had grade 2 and 10% had grade 3. Conclusion: Physician treating the type II DM cases having raised lipid and LFT should have a high suspicion of NAFLD. Early diagnosis and treatment of NAFLD will help in minimizing further complications and will have a good prognosis for the disease.

Risk of fractures and postfracture mortality in 3980 people with primary biliary cholangitis: A population-based cohort study.

Morbidity in primary biliary cholangitis (PBC) is multifactorial. Osteoporosis related to cholestasis is an extrahepatic complication of PBC. It is not fully established to what extent people with PBC have an increased risk for fractures, and if mortality after a fracture is increased, compared to the general population. All Swedish people with PBC diagnosed between 2001 and 2016 were identified from the National Swedish Patient Register using ICD-10 codes. Incident fractures were ascertained in the same register and compared to matched controls from the Swedish general population (1:10 for age, sex, and municipality). Cox regression was used to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation). People with PBC (n=3980) showed a higher risk of fractures at all-time points during follow-up compared to matched controls (n=37,196), which was seen both in men and women. At 5 years of follow-up, the cumulative incidence of any fracture in people with PBC was 16.8% (95% confidence interval [CI]=15.6-18.1), compared to 11.6% (95%CI=11.3-12.0) in controls. The rate of osteoporotic fractures was particularly high (adjusted Hazard ratio [aHR]=1.9; 95%=CI 1.7-2.0). The 30-day as well as the 1-year mortality after a fracture was significantly higher in people with PBC compared to controls that also experienced a fracture (aHR=2.2; 95%CI=1.5-3.2; aHR=2.0; 95%CI 1.7-2.4). People with PBC have a significantly higher risk of fractures and postfracture mortality compared to matched controls from the general population.

Clinical and pathophysiological understanding of the hepatorenal syndrome: Still wrong or still not exactly right?

The hepatorenal syndrome (HRS) is one major extrahepatic complication of end-stage liver diseases. While circulatory dysregulation is considered as primary etiology for HRS, cirrhosis-related (systemic) inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development. Exclusion of other causes of acute kidney injury (AKI) is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites. However, the pathophysiology of HRS is not understood completely and there are still limited therapeutic options. Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function. The interplay between systemic inflammation and the onset of kidney-related hypometabolism may have a key role and needs to be studied in depth. This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.

The Inter-Organ Crosstalk Reveals an Inevitable Link between MAFLD and Extrahepatic Diseases

Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed as a new definition for fatty liver. MAFLD is characterized by the inclusion criteria of metabolic abnormality. Therefore, MAFLD is expected to identify patients at high risk of extra-hepatic complications. In this review, we focus on the relationships between MAFLD and multi-organ diseases. We also describe the pathogenic mechanisms of the inter-organ crosstalk.

Metabolic Associated Fatty Liver Disease as a Risk Factor for the Development of Central Nervous System Disorders

MAFLD/NAFLD is the most ordinary liver disease categorized by hepatic steatosis with the increase of surplus fat in the liver and metabolic liver dysfunction, which is associated with bigger mortality and a high medical burden. An association between MAFLD/NAFLD and central nervous system disorders including psychological disorders has been demonstrated. Additionally, MAFLD/NAFLD has been correlated with various types of neurodegenerative disorders such as amyotrophic lateral sclerosis or Parkinson’s disease. Contrasted to healthy controls, patients with MAFLD/NAFLD have a greater prevalence risk of extrahepatic complications within multiple organs. Dietary interventions have emerged as effective strategies for MAFLD/NAFLD. The PI3K/AKT/mTOR signaling pathway involved in the regulation of Th17/Treg balance might promote the pathogenesis of several diseases including MAFLD/NAFLD. As extrahepatic complications may happen across various organs including CNS, cooperative care with individual experts is also necessary for managing patients with MAFLD/NAFLD.

Non-Hodgkin's Lymphoma as an Extrahepatic Manifestation after Achieving Sustained Virologic Response for Hepatitis C Viral Infection

Hepatitis C virus is a hepatotropic and lymphotropic virus, triggering B-cells and promoting B lymphocyte proliferation. The association between chronic HCV infection and different lymphoproliferative disorders is well known. Antiviral therapy for HCV, including direct acting antivirals, has been proven as effective therapy of HCV-related lymphomas. So far, only few cases of lymphoma after HCV eradication have been reported in the literature. We report a series of 3 cases with HCV-related liver cirrhosis, two of them with sustained virologic response 12 weeks after direct acting antiviral therapy and one with spontaneous eradication of HCV infection, that were diagnosed with large B cell non-Hodgkin’s lymphoma, that are still in remission actually, with a favorable evolution. Engaging the multidisciplinary team is tremendously important, since the diagnosis and management of those cases are successfully made by close collaboration between the gastroenterologist, hematologist, radiologist and pathologist, using imaging techniques, histopathological and immunohistochemical analysis. In the era of highly effective and safe direct acting antivirals, achieving sustained virologic response has been proven to prevent hepatic and extrahepatic malignant complications of chronic HCV infection, including lymphoma. However, recent reports showing the persistent risk for hepatic malignancy in some rare cases, demonstrate that HCV eradication is not the end point and this could be also in line with our cases of extrahepatic non-Hodgkin’s lymphoma.

Clinical Manifestations of Hepatitis E.

The clinical manifestations of hepatitis E are similar to those of other types of viral hepatitis. While acute hepatitis E is usually self-limited, pregnant women and chronic liver disease patients suffering from acute hepatitis E usually present with severe clinical manifestations that may develop into fulminant hepatic failure. Chronic HEV infection is typically seen in organ transplant patients; most HEV cases are asymptomatic and rarely display jaundice, fatigue, abdominal pain, fever, fatigue, or ascites. The clinical manifestations of HEV infection in neonates are diverse and have varied clinical signs, biochemistry, and virus-biomarkers. Lastly, the extrahepatic manifestations and complications of hepatitis E are in need of further study.

Novel metabolic phenotypes for extrahepatic complication of nonalcoholic fatty liver disease.

Phenotypic heterogeneity among patients with NAFLD is poorly understood. We aim to identify clinically important phenotypes within NAFLD patients and assess the long-term outcomes among different phenotypes. We analyzed the clinical data of 2311 participants from the Third National Health and Nutrition Examination Survey (NHANES III) and their linked mortality data through December 2019. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other liver diseases and excess alcohol use. A 2-stage cluster analysis was applied to identify clinical phenotypes. We used Cox proportional hazard models to explore all-cause and cause-specific mortality between clusters. We identified 3 NAFLD phenotypes. Cluster 1 was characterized by young female patients with better metabolic profiles and lower prevalence of comorbidities; Cluster 2 by obese females with significant insulin resistance, diabetes, inflammation, and advanced fibrosis and Cluster 3 by male patients with hypertension, atherogenic dyslipidemia, and liver and kidney damage. In a median follow-up of 26 years, 989 (42.8%) all-cause mortality occurred. Cluster 1 patients presented the best prognosis, whereas Cluster 2 and 3 had higher risks of all-cause (Cluster 2-adjusted HR: 1.48, 95% CI: 1.16-1.90; Cluster 3-adjusted HR: 1.29, 95% CI: 1.01-1.64) and cardiovascular (Cluster 2-adjusted HR: 2.01, 95% CI: 1.18-3.44; Cluster 3-adjusted HR: 1.75, 95% CI: 1.03-2.97) mortality. Three phenotypically distinct and clinically meaningful NAFLD subgroups have been identified with different characteristics of metabolic profiles. This study reveals the substantial disease heterogeneity that exists among NAFLD patients and underscores the need for granular assessments to define phenotypes and improve clinical practice.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection.

Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and is associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, and increased risk of mortality. In addition to liver-related morbidities, HCV is also associated with several extrahepatic manifestations, including mixed cryoglobulinemia, diabetes mellitus, cardiocerebrovascular disease, lymphoma, and autoimmune diseases. These non-liver-related complications of HCV increase the complexity of this disease and can contribute to the economic burden, morbidity, quality of life, and mortality throughout the world. Therefore, understanding how this virus can contribute to each extrahepatic manifestation is worth investigating. Currently, the advancement of HCV treatment with the advent of direct-acting anti-viral agents (DAAs) has led to a high cure rate as a result of sustained virologic response and tremendously reduced the burden of extrahepatic complications. However, HCV-associated extrahepatic manifestations remain a relevant concern, and this review aims to give an updated highlight of the prevalence, risk factors, associated burdens, and treatment options for these conditions.

Trimethylamine N-Oxide Levels in Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) represents an entity with an increasing prevalence which is characterized by significant hepatic and extrahepatic complications. Its pathophysiology is multifactorial, with gut dysbiosis being considered a major determinant. In this systematic review and meta-analysis, we tried to evaluate the association between the major gut microbial metabolite trimethylamine N-oxide (TMAO) and NAFLD. We performed a literature search for studies that determined circulating TMAO in patients with and without NAFLD. The database search identified 136 studies, and upon application of the exclusion criteria, 7 studies with 7583 individuals (NAFLD 2923, control 4660) were ultimately included in the meta-analysis. Compared to the control group, NAFLD patients had significantly higher circulating TMAO (SMD: 0.66, 95% CI -0.12 to 1.21, p = 0.02, I2: 94%). The results remained unaffected after the exclusion of one influential study. The subgroup analysis revealed significantly higher TMAO in individuals with histologically proven NAFLD and in studies measuring TMAO with high-performance liquid chromatography. No differences were observed according to the study design or study region. However, funnel plot asymmetry was observed, indicating publication bias. In conclusion, patients with NAFLD had increased levels of TMAO, a hazardous gut microbial metabolite, suggesting its important role in the gut-liver interaction.

Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

EE131 Cost-Effectiveness Analysis of Emergency Department-Based HCV Screening and Linkage-to-Care Program

Hepatitis C virus (HCV) is a common infection that causes costly liver and extrahepatic complications. Direct-acting antivirals (DAAs) offer >95% cure rates. Patients at high-risk for HCV infection who presented to the emergency department (ED) at UI Health received HCV screening and linkage to DAA treatment. However, HCV screening in the ED is currently not covered by insurance providers. The aim of this study was to assess the long-term cost-effectiveness of routine HCV screening and linkage to care for high-risk patients in the emergency department from the payer’s perspective.

Transient sinus bradycardia caused by hepatitis A virus: a case report

BackgroundThe most common cause of acute viral hepatitis is the hepatitis A virus (HAV). Millions of people are thought to be infected each year. It is transmitted either by the fecal-oral route or by consuming contaminated food. Extrahepatic complications, notably cardiologic ones, are infrequent. This case report was presented due to the development of HAV-related bradycardia without hypotension in an unvaccinated refugee patient.Case presentationA 9-year-old male presented with the complaint of jaundice and vomiting. There was no history of fever, diarrhea, or abdominal pain. A precise knowledge of suspected food intake is lacking. There was no pathological examination finding except jaundice. Total bilirubin, direct bilirubin, aspartate aminotransferase, and alanine aminotransferase levels were high. The coagulation test was normal. Anti-HAV-IgM/IgG was positive in the patient with suspicious viral hepatitis. In the follow-up, the heart rate decreased to 43 beats/min during sleep and 46 beats/min when awake. Cardiological examination and tests were within normal limits. Hypotension was not accompanied. In the follow-up, bradycardia and impaired liver function tests regressed. The patient was discharged on the 10th day.ConclusionsCardiologic complications are rare, and patients diagnosed with acute hepatitis A should be monitored. The most effective way of protection from the hepatitis A virus is vaccination.

Approach to the Patient With Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), causing substantial burden from hepatic and extrahepatic complications. However, endocrinologists often follow people who are at the highest risk of its more severe form with nonalcoholic steatohepatitis or NASH (i.e., T2D or obesity with cardiometabolic risk factors). Endocrinologists are in a unique position to prevent cirrhosis in this population with early diagnosis and treatment. This work aims to offer endocrinologists a practical approach for the management of patients with NAFLD, including diagnosis, fibrosis risk stratification, and referral to hepatologists. (1) An asymptomatic patient with obesity and cardiometabolic risk factors, found to have hepatic steatosis; (2) a patient with T2D and NASH with clinically significant liver fibrosis; and (3) a liver transplant recipient with a history of NASH cirrhosis, with significant weight regain and with recurrent NAFLD on the transplanted organ. NASH can be reversed with proper management of obesity and of T2D. While no agents are currently approved for the treatment of NASH, treatment should include lifestyle changes and a broader use of structured weight-loss programs, obesity pharmacotherapy, and bariatric surgery. Diabetes medications such as pioglitazone and some glucagon-like peptide 1 receptor agonists may also improve liver histology and cardiometabolic health. Sodium-glucose cotransporter-2 inhibitors and insulin may ameliorate steatosis, but their effect on steatohepatitis remains unclear. Awareness by endocrinologists about, establishing an early diagnosis of fibrosis (ie, FIB-4, liver elastography) in patients at high-risk of cirrhosis, long-term monitoring, and timely referral to the hepatologist are all critical to curve the looming epidemic of cirrhosis from NAFLD.

The Liver Maximum Capacity Test (LiMAx) Is Associated with Short-Term Survival in Patients with Early Stage HCC Undergoing Transarterial Treatment.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are recommended to treat patients with early or intermediate hepatocellular carcinoma (HCC). The liver maximum capacity test (LiMAx) has been supposed to predict the risk of post-interventional liver failure. We investigated the correlation of LiMAx with short-term survival as primary endpoint and the occurrence of adverse events after therapy as secondary endpoint. Our study cohort prospectively included 69 patients receiving TACE (n = 57) or TARE (n = 12). LiMAx test and serological analyses were performed on the day before and 4 weeks after treatment. Hepatic and extrahepatic complications were monitored for 4 weeks. The LiMAx results were not associated with altered liver function and the occurrence of adverse events. The survival rates of patients with BCLC A with LiMAx ≤ 150 μg/kg/h were lower after 30 days (75.0 ± 15.3% vs. 100%, p = 0.011), 90 days (62.5 ± 17.7% vs. 95.8 ± 4.1%, p = 0.011) and 180 days (50.0 ± 17.7% vs. 95.8 ± 4.1%, p = 0.001) compared to those with higher LiMAx levels. The LiMAx test is not suitable to predict liver function abnormalities or the occurrence of complications 4 weeks after therapy but enables the identification of patients with early stage HCC and reduced short-term survival after treatment.

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58–72 years); 43% females). Median follow-up was 2 years (1–3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (β = 1.16, p < 0.001) and three years (β = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment.

A Multidisciplinary Approach and Current Perspective of Nonalcoholic Fatty Liver Disease: A Systematic Review

In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC)and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMIof >40 kg/m2 and >35 kg/m2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.

Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study

Aims/hypothesisSerum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes.MethodsWe used cross-sectional data from the Maastricht Study (n=1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes.ResultsIHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17], respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3]) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6]). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results.Conclusions/interpretationIn this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine.Graphical abstract

Efficacy and safety of endovascular therapy for delayed hepatic artery post-pancreatectomy hemorrhage: development of extrahepatic collateral circulation and complications of post endovascular therapy

BackgroundEndovascular therapy (ET) for delayed hepatic artery post-pancreatectomy hemorrhage (HA-PPH) may require complete hepatic artery occlusion (HAO). Nonetheless, the development of extrahepatic collateral circulation (EHC) and the relationship between radiological factors (EHC, portal vein stenosis, and HAO) and adverse hepatic events after ET remain unclear. This study aimed to evaluate the efficacy and safety of ET for delayed PPH and examine the development of EHC.MethodsA total of 19 ET cases for delayed HA-PPH were reviewed. Hepatic adverse events, portal vein stenosis, HAO, and mortality rate after ET were evaluated. Moreover, EHC from the left gastric artery (LGA), right inferior phrenic artery (RIPA), left inferior phrenic artery (LIPA), right internal thoracic artery (RITA), left internal thoracic artery (LITA), renal artery (RA), omental artery (OA), intercostal artery (IA), and branch of superior mesenteric artery (BSMA) was assessed using angiogram and computed tomography angiography (CTA).ResultsAll cases were successfully treated using transcatheter arterial embolization (n = 17) and stent-graft placement (n = 2) without mortality. EHC from the LGA (8/19), RIPA (10/19), LIPA (4/19), and RITA (3/19) was observed on post-ET CTA. The incidence of hepatic adverse events was significant in the group with both HAO and portal vein stenosis (p < 0.001) and absence of EHC from LIPA and RITA (p < 0.05).ConclusionET for delayed HA-PPH might be effective and safe. While avoiding both HAO and portal vein stenosis is important, the development of EHCs from LIPA and RITA may prevent hepatic adverse events after ET.

Novel metabolic classification for extrahepatic complication of metabolic associated fatty liver disease: A data-driven cluster analysis with international validation

BackgroundTraditional classification systems of metabolic-associated fatty liver disease (MAFLD) do not account for the high rate of extrahepatic complications. To create a new classification of MAFLD using metabolic parameters to identify risks of complications more accurately. MethodsThe retrospective study included MAFLD patients from the First Affiliated Hospital of Sun Yat-sen University for model development, and the model was validated respectively using Chinese cohort and UK Biobank database. Cluster analysis with k-means cluster was built using age, body mass index (BMI), glycosylated hemoglobin (HbA1c), total cholesterol/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride, and lipoprotein(a) [Lp(a)] levels. Cox regression models were used to compare the risk of type 2 diabetes (T2DM), chronic heart disease (CHD), stroke and mortality between the clusters. Results1038 MAFLD patients from cross-sectional population were recruited for the model derivation, with 10,451 cases (33.4 % of MAFLD) from Chinese cohort and 304,141 cases (34.9 % of MAFLD, 1010 cases with magnetic resonance imaging proton density fat fraction measurement [MRI-PDFF]) from the international cohort validated. Five replicable clusters of MAFLD patients were identified: Cluster 1(mild obesity and dyslipidemia-related), Cluster 2 (age related), Cluster 3 (severe insulin resistance-related), Cluster 4[high Lp(a)-related], and Cluster 5 (severe mixed hyperlipidemia-related). Patients in different clusters exhibited differences in the development of T2DM, CHD, stroke and all-causes mortality. Patients in Cluster 3 had significantly worst survival outcomes and higher risks of T2DM and CVD than those in other clusters. ConclusionThe novel classification offers improved discrimination of new-onset MAFLD patients with different metabolic complications.