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International Journal Of Hepatology[JOURNAL]

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Acyl-CoA Thioesterase 1 Contributes to Transition of Steatosis to Metabolic-Associated Steatohepatitis.

Pasini E, Baciu C, Angeli M … +11 more , Arendt B, Pellegrina D, Reimand J, Patel K, Tomlinson G, Mazhab-Jafari MT, Kotra LP, Fischer S, Allard JP, Humar A, Bhat M

Int J Hepatol · 2024 · PMID 39624175 · Full text

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) has become the leading cause of chronic liver disease, but there has been no approved pharmacotherapy to date. METHODS: We used a network analysis appro... BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) has become the leading cause of chronic liver disease, but there has been no approved pharmacotherapy to date. METHODS: We used a network analysis approach to delineate protein-protein interactions that contribute to the transition from steatosis to MASH, in order to identify and target this transition as a potential pharmacotherapeutic strategy. Acyl-CoA thioesterase 1 (ACOT1) was identified as a critical node in the protein-protein interaction (PPI) network of the transition from steatosis to MASH in patient samples. ACOT1 overexpression and silencing effects were tested on C57BL/6 mice exposed to high-fat diet (HFD) and inoculated with an adenoviral system to modulate expression. Transcriptomic and untargeted lipidomic profiles were performed on the mouse livers. RESULTS: ACOT1 expression was 3-fold higher in MASH as compared to steatosis. In patient samples, was significantly correlated with the severity of MASH as reflected by the nonalcoholic fatty liver disease score. Experimental validation showed that downregulation of ACOT1 resulted in decreased lipid accumulation and prevention of MASH . Conversely, upregulation of ACOT1 via an adenoviral vector resulted in development of MASH, whereas control mice only developed steatosis. Lipidomic analysis revealed glycerophospholipids to be especially abundant in MASH accelerated by ACOT1 upregulation. CONCLUSION: These results suggest that ACOT1 contributes to the transition from steatosis to MASH through modulation of glycerophospholipid accumulation and its potential as a novel therapeutic target in MASH. This trial is registered with NCT02148471.

Utilization of Contrast-Enhanced Ultrasound in Diagnosis of Focal Liver Lesions.

Salama F, Thakral N, Leyson CD … +6 more , Konjeti V, Benrajab K, Hawk G, Fouch H, Gedaly R, Khurana A

Int J Hepatol · 2024 · PMID 39484627 · Full text

: Focal liver lesions (FLL) are one of the most common indications for hepatology and hepatobiliary surgery consultation. In this retrospective study, we aim to assess if contrast-enhanced ultrasound (CEUS) can address d... : Focal liver lesions (FLL) are one of the most common indications for hepatology and hepatobiliary surgery consultation. In this retrospective study, we aim to assess if contrast-enhanced ultrasound (CEUS) can address diagnostic dilemmas in the evaluation of indeterminate liver lesions by identifying characteristics of indeterminate FLL on CEUS and correlating these with cross-sectional imaging and pathology findings. : We retrospectively reviewed all patients who underwent CEUS evaluation for liver lesions over a 28-month period (Oct 2020 to Jan 2023) at the University of Kentucky. To assess the relationship between CEUS results and the corresponding CT, MRI, and/or pathologic findings, the McNemar-Bowker tests were performed. : Twenty-nine patients were included (after two exclusions from a total of 31). Mean age was 54 years, 62% were female, and 48% had underlying cirrhosis. Of the 29 patients with initial cross-sectional imaging, the initial results showed malignancy or likely malignant lesion in 6 patients and benign or likely benign lesion in 6 patients. The remaining 17 patients had inconclusive/indeterminate results. CEUS clarified an "indeterminate" CT/MRI result 15 times out of 17 (88.2%), moving the diagnosis to "benign" 11 times while suggesting "malignant" only four times. When aggregating indeterminate cross-sectional results with either benign or malignant categories suggested by CEUS, CEUS never reversed a benign CT/MRI diagnosis but often reversed a malignant CT/MRI diagnosis. : CEUS provided a definitive diagnosis of indeterminate liver lesions in approximately 90% of patients and avoided the need for biopsy in most patients. In cases where the liver lesions were biopsied, CEUS accurately distinguished malignant versus benign lesions as confirmed by biopsy findings. CEUS, therefore, has the potential to provide a precise diagnosis for the majority of indeterminate lesions.

Anatomical Variations of the Gallbladder and Bile Ducts: An MRI Study.

Yason K, Gonza KG, Michael O … +3 more , William B, Munabi I, Michael K

Int J Hepatol · 2024 · PMID 39464874 · Full text

The anatomy of the biliary tree is complex with anatomical variations which can be found in ~50% of the patients. Existing research on these variations primarily stems from studies in developed countries, with uncertain... The anatomy of the biliary tree is complex with anatomical variations which can be found in ~50% of the patients. Existing research on these variations primarily stems from studies in developed countries, with uncertain applicability to the Ugandan population due to noted ethnic differences in incidence rates. The study was aimed at describing the anatomical variations of the gallbladder and bile ducts. This retrospective cross-sectional study conducted at Kampala MRI Centre from January 2017 to December 2022 analyzed MRCP images and reports from 231 patients to document gallbladder and bile duct variations. 53.2% of patients exhibited typical cystic duct anatomy, and 51% had Type 1 variations in intrahepatic ducts. Importantly, the study identified a significant correlation between age and common bile duct diameter. The findings showed various anatomical variations that were slightly higher in the study population than those reported in the literature. This study emphasizes the critical need for comprehensive knowledge to enhance surgical safety, minimize iatrogenic trauma, and improve the accuracy of diagnostic imaging and hepatobiliary procedures.

The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies.

Yaghmaei H, Bahanesteh A, Soltanipur M … +3 more , Takaloo S, Rezaei M, Siadat SD

Int J Hepatol · 2024 · PMID 39444759 · Full text

One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiolog... One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.

Evaluation of Noninvasive Tools for Predicting Esophageal Varices in Patients With Cirrhosis at Tygerberg Hospital, Cape Town.

Kwape L, Gabriel S, Abdelsalem A … +10 more , Rose P, Bathobakae L, Peterson D, Moodley D, Parker M, Moolla S, Parker A, Siamisang K, Van Rensburg C, Fredericks E

Int J Hepatol · 2024 · PMID 39296589 · Full text

In patients with cirrhosis, esophageal variceal hemorrhage (EVH) is a devastating consequence of portal hypertension (PH). Upper endoscopy is considered the gold standard for the detection and diagnosis of esophageal var... In patients with cirrhosis, esophageal variceal hemorrhage (EVH) is a devastating consequence of portal hypertension (PH). Upper endoscopy is considered the gold standard for the detection and diagnosis of esophageal varices (EVs), despite being invasive and costly. This study was aimed at identifying and evaluating the diagnostic accuracy of noninvasive tools in predicting EVs in patients with compensated cirrhosis. This cross-sectional study included 50 patients with compensated cirrhosis at the Tygerberg Hospital Gastroenterology Clinic in Cape Town between November 2022 and May 2023. We collected clinical, anthropometric, and laboratory data from patients' physical and electronic charts. All patients underwent an abdominal ultrasound, vibration-controlled transient elastography (VCTE) to assess liver and splenic stiffness, and upper endoscopy. In this comparative study, we evaluated the diagnostic accuracy of different noninvasive tools in detecting EVs in patients with compensated cirrhosis. Of the 50 patients included in the study, 30 (60%) were female and 20 (40%) were male. The patients' age ranged from 18 to 83, with a mean age of 46.6 years. Cirrhosis was mainly due to alcohol use ( = 11, 22%), hepatitis B virus (HBV) infection ( = 11, 22%), and autoimmune hepatitis ( = 10, 20%). The patients included in the study were divided into two subgroups: with ( = 34, 68%) or without ( = 16, 32%) EVs. Statistically significant differences were detected between groups in platelet count (PC), liver stiffness measurement (LSM), spleen stiffness measurement (SSM), portal vein diameter (PVD), bipolar spleen diameter (SBD), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), platelet/bipolar spleen diameter ratio (PSR), liver stiffness-spleen size-platelet ratio (LSPS), liver stiffness-spleen stiffness-platelet ratio score (LSPS), and spleen stiffness-spleen size-platelet ratio score (SSPS) ( < 0.001). The highest diagnostic precision was observed with SSM (96%), SSPS (96%), LSPS (94%), LSPS (94%), PSR (94%), and PC (92%). SBD (88%), LSM (86%), APRI (82%), and FIB-4 (82%) had the lowest diagnostic accuracy. : SSM and SSPS have the highest diagnostic accuracy for predicting the presence of EVs in patients with compensated cirrhosis. LSPS, LSPS, and PSR come second at 94%. We recommend SSM and SSPS in institutions with transient elastography equipped with the software necessary to measure splenic stiffness. We introduce and propose LSPS as a novel composite score for predicting the presence of EVs in patients with compensated cirrhosis. Large-sample-size studies are needed to validate these prediction scores and to allow direct comparison with Baveno VII. These prediction tools can help clinicians avoid unnecessary endoscopic procedures in patients with compensated cirrhosis, especially in developing countries with limited resources such as South Africa.

Impact of Renal Replacement Therapy on Outcomes of Living Donor Liver Transplantation for Acute Liver Failure: A Cohort Study.

Bhatti ABH, Ul Haq N, Mehmood N … +8 more , Hassan D, Ahmed A, Malik WT, Zia HH, Salih M, Khan NY, Ilyas A, Khan NA

Int J Hepatol · 2024 · PMID 39268546 · Full text

Despite the promising role of renal replacement therapy (RRT) in acute liver failure (ALF), high-risk patients need liver transplantation and remain at risk for death due to cerebral complications. The objective of this... Despite the promising role of renal replacement therapy (RRT) in acute liver failure (ALF), high-risk patients need liver transplantation and remain at risk for death due to cerebral complications. The objective of this study was to report outcomes of living donor liver transplantation (LDLT) for ALF with perioperative RRT. This was a single-center retrospective cohort study. Out of 1167 LDLTs, 24 patients had ALF and met the King's College criteria for transplantation. They were categorized into no-RRT ( = 13) and RRT ( = 11) groups. We looked at 1-year posttransplant survival in these patients. The median serum ammonia level at the time of transplant in the no-RRT and RRT groups was 259.5 mcg/dL (222.7-398) and 70.6 mcg/dL (58.1-92.6) ( = 0.005). In the RRT group, serum ammonia level < 100 mcg/dL was achieved in all patients. Seven (53.8%) patients in the no-RRT group and 11/11 (100%) in the RRT group were extubated and regained full consciousness after LDLT ( = 0.013). The 90-day mortality was 6/13 (46.1%) and 2/11 (18.1%) ( = 0.211). There was no brainstem herniation-related mortality in the RRT group, that is, 5/13 (38.4%) and 0/11 (0%) ( = 0.030). The 1-year posttransplant survival was also significantly higher in the RRT group ( = 0.031). The use of RRT lowers serum ammonia levels and might reduce posttransplant mortality due to brainstem herniation.

miRNA-221: A Potential Biomarker of Progressive Liver Injury in Chronic Liver Disease (CLD) due to Hepatitis B Virus (HBV) and Nonalcoholic Fatty Liver Disease (NAFLD).

Sutradhar PR, Sultana N, Nessa A

Int J Hepatol · 2024 · PMID 39185365 · Full text

Early detection of progressive liver damage in chronic liver disease (CLD) patients is crucial for better treatment response. Several studies have shown the association of microRNA (miRNA) in the progression of CLD in re... Early detection of progressive liver damage in chronic liver disease (CLD) patients is crucial for better treatment response. Several studies have shown the association of microRNA (miRNA) in the progression of CLD in regulating cell proliferation, fibrosis, and apoptosis as well as in carcinogenesis. The study was aimed at determining the expression of miRNA-221 among different stages of fibrosis in CLD patients due to hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD) and thus evaluate its role as an early biomarker in CLD. A total of 100 participants (75 CLD patients and 25 healthy control) were recruited in this cross-sectional study and divided into four groups, of which 25 as healthy control, 25 in CLD without fibrosis, 25 were CLD with fibrosis, and 25 were CLD with cirrhosis. Total RNA was extracted from plasma followed by cDNA synthesis, and finally, the expression of miRNA-221 was analyzed for its diagnostic potential as a single biomarker using the qRT-PCR method. The plasma level of miRNA-221 was significantly upregulated in different fibrosis stages of CLD ( < 0.05), and this upregulation was positively correlated with the progression of fibrosis ( < 0.05). Significantly increased expression of miRNA-221 was found in NAFLD patients compared to HBV patients in the CLD without fibrosis patient group ( < 0.05), while expression of miRNA-221 was significantly upregulated among HBV patients in the CLD with the fibrosis group. miRNA-221 showed high diagnostic accuracy in discriminating different stages of fibrosis from healthy control ( < 0.05). miRNA-221 may be used as a potential plasma biomarker for early prediction of fibrosis progression in CLD patients.

Survival and Disease Progression in Older Adult Patients With Cirrhosis: A Retrospective Study.

Al-Smadi K, Qureshi A, Buitrago M … +2 more , Ashouri B, Kayali Z

Int J Hepatol · 2024 · PMID 39149542 · Full text

Cirrhosis incidence in older adult patients has been increasing with limited data on their survival. This study is aimed at investigating the survival and disease progression in older adult patients with cirrhosis compar... Cirrhosis incidence in older adult patients has been increasing with limited data on their survival. This study is aimed at investigating the survival and disease progression in older adult patients with cirrhosis compared to younger patients. This is a retrospective single-center study. Patients aged above 50 with a confirmed diagnosis of cirrhosis based on biopsy, FibroSure test, splenomegaly, and low platelets < 120 × 10/L) or imaging findings including FibroScan were included. Patients with active substance abuse, transjugular intrahepatic portosystemic shunt (TIPS), prior spontaneous bacterial peritonitis (SBP), variceal hemorrhage, model for end-stage liver disease-Na (MELD - Na) ≥ 20, had liver transplantation, malignancy except for squamous cell carcinoma, and other comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and end-stage kidney disease with glomerular filtration rate (GFR) < 30 were excluded. Patients' records from the liver clinic were reviewed and demographics, laboratory, and compensation and decompensation status were collated. Patients were separated into two groups based on age 50-64 years and age ≥ 65. The primary endpoint was death, and the secondary endpoint was disease progression measured by the baseline to 12-month increase in MELD-Na score. The Kaplan-Meier analysis was conducted to compare the survival between the two groups. Cox regression analysis was performed to identify independent risk factors for poor survival. A total of 191 patients diagnosed with cirrhosis met the inclusion and exclusion criteria. There were 80 patients aged 50-64 years and 111 patients aged ≥ 65 years. Significantly shorter survival times were seen among patients aged ≥ 65 years compared to those aged 50-64 years (73.3 ± 4.8 vs. 151.5 ± 22.7; < .001). Age of diagnosis ≥ 65 years ( < 0.001), male gender ( = .013), body mass index (BMI) < 30 ( = 0.005), and decompensation ( = 0.008) were found to be independent risk factors for poor survival. MELD-Na scores increased significantly in 12 months of follow-up from baseline, but only in patients with decompensated cirrhosis ( = 0.013). Cirrhotic patients aged ≥ 65 years have significantly poor survival compared to younger patients. A prospective study is needed to further investigate the effect of age and obesity on survival and disease progression in older adult patients with cirrhosis.

Macrophage-2-Binding Protein Glycosylation Isomer (M2BPGi) and AGAP Score as Markers of Noninvasive Test for Liver Fibrosis versus FibroScan in Chronic Hepatitis B Patients: A Retrospective Observational Study.

Pramono LK, Tjandrawati A, Turbawaty DK … +5 more , Rostini T, Bestari MB, Haryono, Budiman D, Nugraha P

Int J Hepatol · 2024 · PMID 38882242 · Full text

BACKGROUND: Liver biopsy as the gold standard for assessing the degree and diagnosis of fibrosis still has significant drawbacks, which make the emergence of a much less invasive diagnostic marker possible. M2BPGi levels... BACKGROUND: Liver biopsy as the gold standard for assessing the degree and diagnosis of fibrosis still has significant drawbacks, which make the emergence of a much less invasive diagnostic marker possible. M2BPGi levels and the AGAP score, the two newest serological markers, are known to have good sensitivity for detecting liver fibrosis. This study is aimed at determining the validity of examining M2BPGi levels and AGAP scores on the Fibroscan examination as markers of noninvasive test for liver fibrosis in chronic hepatitis B patients. METHODS: This is an observational, descriptive study with a retrospective design. This study used secondary data taken from medical records and blood specimen research materials of outpatients at the Hepatology Gastroenterology Polyclinic at a tertiary general hospital in West Java, Indonesia, with a diagnosis of chronic hepatitis B. RESULTS: There were 109 research subjects included. There were 73 (66.9%) subjects with no- or low-grade fibrosis and 36 (33.1%) with advanced fibrosis. The sensitivity and specificity of the M2BPGi were 88.9% and 61.6% (PPV 55.3%; NPV 91.8%; AUC 0.753), while the AGAP score was 47.2% and 100% (PPV 100%; NPV 79.3%; AUC 0.736). The combined M2BPGi level and the AGAP score showed a sensitivity of 80.9% and a specificity of 100% (PPV 100%; NPV 91.8%; AUC 0.905). CONCLUSION: The AGAP score and M2BPGi levels together are a better way to measure the degree of liver fibrosis in people with chronic hepatitis B than either M2BPGi or the AGAP score alone.

Knowledge Gaps and Determination of Attitude and Practice among Medical Students toward Hepatitis B Infection: A Nationwide Cross-Sectional Study.

Alaridah N, Jarrar RF, Joudeh RM … +5 more , Al-Abdallat H, Ismail L, Alnajjar Z, Jum'ah M, Abu-Humaidan AH

Int J Hepatol · 2024 · PMID 38550614 · Full text

INTRODUCTION: As reported by the World Health Organization (WHO), annually, there are 1.5 million new infections, with more than 290 million people living with chronic hepatitis B diseases in 2019. Medical students (MSs)... INTRODUCTION: As reported by the World Health Organization (WHO), annually, there are 1.5 million new infections, with more than 290 million people living with chronic hepatitis B diseases in 2019. Medical students (MSs), a subgroup of health care workers (HCWs), are at high occupational risk for HBV infection since HCWs have a 2-10 times greater risk of getting the virus than the general population. Therefore, they must have a broad understanding of hepatitis B infection. In this study, we aimed to assess the level of knowledge, attitude, and practices among MSs, and to explore its predictors. . A descriptive cross-sectional research was done among MSs, those who finished their infectious disease course. MSs were asked to participate in a self-administered online-structured questionnaire. RESULTS: 612 MSs were enrolled in our study. 67.5% were females, and 36.9% were in their 6th year. Around half of the participants held a high level of knowledge, attitude, and practices toward HBV infection. MSs in the last year of the study who encountered HBV patients showed to have better knowledge. Male MSs who encountered HBV patients and took extra HBV courses showed better attitudes. High practice level among MSs was associated with being in the 6th year and taking extra HBV courses. CONCLUSIONS: This study demonstrated a satisfactory level of knowledge, attitude, and practices toward HBV infection among MSs. However, awareness must be enhanced in some areas especially transmission routes of HBV. Thus, it will strengthen the level of attitude and practices to omit the effect of the stigma while delivering care to HBV patients.

The Efficacy of On-Site Integration Screening and Microelimination Programs for Chronic Hepatitis C in a Detection Center: A Comparison of the Treatment Outcomes and Characteristics of Incarcerated Patients and Outpatients.

Chang HY, Wang SH, Kuo HT … +8 more , Sheu MJ, Feng IC, Ho CH, Chen JY, Sun CS, Chen CH, Lin CY, Yang CC

Int J Hepatol · 2024 · PMID 38510786 · Full text

We aimed to analyze the different patient characteristics and treatment outcomes (such as sustained viral response, SVR) between incarcerated patients with chronic hepatitis C (CHC) and those with CHC from the outpatient... We aimed to analyze the different patient characteristics and treatment outcomes (such as sustained viral response, SVR) between incarcerated patients with chronic hepatitis C (CHC) and those with CHC from the outpatient department through an on-site integrated screening and microelimination program in a detection center. In this retrospective study, which ran from May 2021 to April 2022, we included 32 consenting male prisoners aged at least 20 years who were willing to participate in the study. Members of the control group (who received DAAs in an outpatient setting) were selected from the treated CHC patient databank of individuals who received DAA regimens at Chi Mei Hospital between January 2021 and December 2022. The patients in the two groups did not differ significantly in terms of age, FIB-4 score, HCV RNA, HBV coinfection, hemogram findings, coagulation profiles, and renal function tests. However, the patients in the incarcerated group had a significantly different genotype distribution compared to the control group, significantly lower liver enzyme levels, and higher albumin and bilirubin levels compared to those in the control group. The rate of SVR to DAA treatment obtained among incarcerated patients did not differ significantly from that obtained among patients in the control group. Loss to follow-up (for several reasons) is a major reason for treatment discontinuation among these patients.

Severe Hepatotoxicity in Mushroom Poisoning by from Complete Recovery to Liver Transplantation: A Case Series with Review on Liver Function Tests and Liver Histopathology.

Anbardar MH, Soleimani N, Kazemi K … +7 more , Jafarpour Z, Hasani M, Mohammadzadeh S, Torfehnezhad P, Jafarian S, Farhadi M, Sardari MS

Int J Hepatol · 2024 · PMID 38288080 · Full text

BACKGROUND: In spite of the scientific evidence supporting health advantages of mushrooms, some of them are seriously poisonous. The clinical picture of mushroom intoxication ranges from minor gastrointestinal symptoms t... BACKGROUND: In spite of the scientific evidence supporting health advantages of mushrooms, some of them are seriously poisonous. The clinical picture of mushroom intoxication ranges from minor gastrointestinal symptoms to organ failure, such as liver failure and death. METHOD: We provided demographics, clinicopathological characteristics, applied treatments, and outcomes of mushroom poisoning by Lepiota species in a series of 18 cases that were referred from Kermanshah and Lorestan provinces to Abu-Ali-Sina Hospital, Shiraz, Iran. Clinical and paraclinical data were collected by taking history and reviewing of medical documents. Pathologic findings were extracted through a review of hematoxylin and eosin pathologic slides. RESULTS: The patients were between the ages of 18 and 67 years, composed of ten females and eight males. The most frequent clinical manifestations were nausea and vomiting followed by abdominal pain. Four cases presented decreased consciousness on admission. One of them passed away. Three other cases underwent liver transplantation, two of them died after transplantation, and one fully recovered without any major issues. All instances had elevated ALT levels, which ranged from 44 to 9,140 IU/L (mean: 3259 ± 2476), with most of them also having concurrent AST elevations (mean: 1,361 ± 1,532). Only few patients had modest elevations in alkaline phosphatase. Total and direct bilirubin elevations up to 47.6 and 24 mg/dL, respectively, were found in most cases. Decreased total protein and albumin concentrations and increased BUN and creatinine levels were observed in some patients. In addition, some instances revealed increased LDH, increased WBC, decreased hemoglobin, and decreased platelet count. Most patients had increased prothrombin time; hematuria and positive stool occult blood were observed in few patients. Histopathologic examination of three explanted livers revealed massive necrosis with moderate to severe macrovesicular steatosis, significant ductular reaction, and parenchymal inflammation. Other patients followed a recovery process with a considerable drop in liver enzymes, especially ALT, during hospitalization utilizing conservative treatment. They had no liver problems or relevant issues after a two-year follow-up. CONCLUSION: In our study, highly elevated liver enzymes with a significantly high ALT/AST ratio were observed in cases of mushroom poisoning by Lepiota species, leading to fulminant liver failure and death in some cases. These laboratory findings were correlated with liver necrosis and macrovesicular steatosis in explanted livers.

The Use of Noninvasive Velacur® for Discriminating between Volunteers and Patients with Chronic Liver Disease: A Feasibility Study.

Curry MP, Tam E, Schneider C … +3 more , Abdelgelil N, Hassanien T, Afdhal NH

Int J Hepatol · 2024 · PMID 38274398 · Full text

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease is the leading cause of chronic liver disease globally and can progress to cirrhosis, liver failure, and liver cancer. Current AASLD, AGA, and ADA guidelines recommen... BACKGROUND AND AIMS: Nonalcoholic fatty liver disease is the leading cause of chronic liver disease globally and can progress to cirrhosis, liver failure, and liver cancer. Current AASLD, AGA, and ADA guidelines recommend assessment for liver fibrosis in all patients with NAFLD. Serum biomarkers for fibrosis, while widely available, have notable limitations. Imaging-based noninvasive testing for liver fibrosis/cirrhosis is more accurate and is becoming more widespread. METHODS: We evaluated the feasibility of a novel shear wave absolute vibroelastography (S-WAVE) modality called Velacur® for assessing liver stiffness measurement (LSM) for fibrosis and attenuation coefficient estimation (ACE) in differentiating patients with chronic liver disease from normal healthy controls. RESULTS: Fifty-four healthy controls and 89 patients with NAFLD or cured HCV with a prior known LSM of >8 kPa were enrolled, and all subjects were evaluated with FibroScan® and Velacur®. Velacur® was able to discriminate patients with increased liver stiffness as determined by a FibroScan® score of >8 kPa from healthy controls with an AUC of 0.938 (0.88-0.96). For assessment of steatosis in NAFLD patients only, Velacur® could identify patients with steatosis from healthy controls with an AUC of 0.831 (0.777-0.880). The Velacur® scan quality assessment was superior in healthy controls, as compared to patients, and the scan quality, as assessed by the quality factor (QF) and interquartile range (IQR)/median, was affected by BMI. Velacur® was safe and well tolerated by patients, and there were no adverse events. CONCLUSION: Velacur® assessment of liver stiffness measurement and liver attenuation is comparable to results obtained by FibroScan® and is an alternative technology for monitoring liver fibrosis progression in patients with chronic liver disease. This trial is registered with NCT03957070.

Hepatitis C Prevalence on the Rise but Screening at Safety Net Institutions Lagging behind.

Prasa J, Karim SS, Jacob B … +1 more , Mustacchia P

Int J Hepatol · 2023 · PMID 38027071 · Full text

INTRODUCTION: In the United States, the hepatitis C virus (HCV) is a leading contributor to liver-related illnesses and fatalities. Despite effective antiviral medications, acute infections have increased in recent years... INTRODUCTION: In the United States, the hepatitis C virus (HCV) is a leading contributor to liver-related illnesses and fatalities. Despite effective antiviral medications, acute infections have increased in recent years, likely due to IV drug use and the opioid epidemic. Previous guidelines recommended one-time screening for individuals born between 1945 and 1965. The CDC now recommends screening all adults over 18 unless there is a low prevalence in the area. Accurate measurement of HCV prevalence is essential for targeted prevention. In New York, over 100,000 individuals have HCV. We present data on HCV screening at a safety net hospital in Long Island, NY. OBJECTIVE: To identify screening rates for hepatitis C and the exposure prevalence and specific demographics of a community in Long Island, NY. METHODS: We performed a review of all patients seen in our hospital from 2012 to 2019. We identified patients born in the years 1945 to 1965 using our electronic medical record (EMR) system and subsequently analyzed those who were anti-HCV positive. We reviewed their demographics, including age, gender, and ethnicity, as well as their history of intravenous drug use and HIV coinfection status. Basic statistical analysis was used. RESULTS: Our study identified 21,722 patients born between 1945 and 1965 and found that only 8.5% or 1,858 individuals were screened for hepatitis C. Among them, we found that 5.9% (109) tested positive for HCV antibody, with 3.0% (56) having an active infection. Demographic characteristics of those with HCV antibodies included 70.6% male, 53.2% Caucasian, 33.9% Black, and 15.6% persons who inject drugs (PWID). CONCLUSION: Our study findings suggest that a significant portion of patients in our community had missed opportunities for screening in our hospital. Our community had an estimated 5.9% prevalence, higher than the national and state averages. Caucasian men had higher prevalences. This study suggests the need for broader screening initiatives and more focused resource allocation, perhaps to safety net institutions, to decrease the burden of HCV.

Pathology of Hepatocellular Carcinoma and Tumor-Bearing Liver Tissue in Association with Promoter Mutation.

Fischer AK, Semaan A, Wulf AL … +3 more , Vokuhl C, Goltz D, Fischer HP

Int J Hepatol · 2023 · PMID 37593089 · Full text

BACKGROUND: The promoter mutation represents a common and early event in hepatocarcinogenesis, but its linkage to the morphological status of the underlying liver tissue is poorly understood. We analyzed the connection... BACKGROUND: The promoter mutation represents a common and early event in hepatocarcinogenesis, but its linkage to the morphological status of the underlying liver tissue is poorly understood. We analyzed the connection between the histopathological changes in tumor-bearing liver tissue and the occurrence of the promoter mutation in hepatocellular carcinoma (HCC), correlated with clinical data. METHODS: The study cohort comprised 160 histologically confirmed HCC in patients with or without cirrhosis that were investigated for the promoter mutation. We evaluated the frequency of the promoter mutation in patients with HCC with or without cirrhosis and correlated it with potential clinical and histopathological drivers. In particular, we examined tumor-bearing noncirrhotic liver tissue regarding inflammation; the modified histological activity index (mHAI), fibrosis, and steatosis; and its correlation with the frequency of the promoter mutation in HCC. We evaluated overall survival with multivariate Cox regression. Furthermore, we compared hTERT antibody immunohistochemistry and molecular promoter mutation analysis of both HCC and background liver tissue. RESULTS: The promoter mutation was especially related to HCC in cirrhotic compared with noncirrhotic liver ( < 0.001) and independently of cirrhosis in patients ≥ 60 years ( = 0.005). Furthermore, the promoter mutation was associated with cirrhosis caused by alcohol toxicity and hepatitis C virus infection. In noncirrhotic liver tissue, the frequency of -promoter-mutated HCC increased with the degree of inflammation and fibrosis. Nevertheless, 25% of the -promoter-mutated HCC developed in normal liver tissue without HCC risk factors. Multivariate Cox regression analysis did not reveal an influence of the promoter mutation in HCC on overall survival at 3, 5, and 16 years. Immunohistochemical analysis with the hTERT antibodies LS-B95 and 2D8 in -promoter-mutated HCC and -wildtype HCC showed a mildly stronger immunoreaction compared with the tumor-bearing liver tissue (LS-B95: < 0.01, 2D8: < 0.01). CONCLUSIONS: Our study reveals a connection between pathological changes in tumor-bearing liver tissue and the promoter mutation in most HCC, even in noncirrhotic liver tissue. Immunohistochemical hTERT antibodies do not discriminate between -promoter-mutated and wildtype HCC.

Progressive Familial Intrahepatic Cholestasis: A Descriptive Study in a Tertiary Care Center.

Alsohaibani FI, Peedikayil MC, Alfadley AF … +3 more , Aboueissa MK, Abaalkhail FA, Alqahtani SA

Int J Hepatol · 2023 · PMID 37520499 · Full text

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that results from defective mechanisms of bile secretion. We aim to describe different types of PFIC and their clinical features... BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that results from defective mechanisms of bile secretion. We aim to describe different types of PFIC and their clinical features, treatment modalities, and outcomes in Saudi Arabia. . This is a retrospective study of all patients diagnosed with PFIC at King Faisal Specialist Hospital and Research Center in Riyadh from January 1, 2002, to December 31, 2021. All relevant information was collected from patient charts and transferred into the REDcap® database for statistical analysis. RESULTS: A total of 79 patients were identified with PFIC, and PFIC type 3 was the most common (59.5%), followed by PFIC type 2 (34.2%), PFIC type 1 (5.1%), and PFIC type 4 (1.3%). Males and females were affected in 54.4% and 45.6%, respectively. Mutations in ATP8B1, ABCB11, and ABCB4 genes were observed in PFIC type 1, PFIC type 2, and PFIC type 3, and loss of function in a variant of TJP2 was detected in PFIC type 4, respectively. A total of 51 (64.6%) patients underwent liver transplantation: three patients (3/4) with PFIC type 1 (75%), twenty patients (20/27) with PFIC type 2 (74.1%), twenty-seven patients (27/47) with PFIC type 3 (57.4%), and one patient with PFIC type 4 (100%). The mean duration of disease before transplantation was 53.9 ± 67 months with a median of 30 months. Following liver transplantation, symptomatic control was achieved in 47 patients (92.2%). Recurrence after transplantation occurred in 4 patients (7.8%) within an average of 22.5 months and a median of 17 months. CONCLUSION: PFIC is considered a rare disorder in Saudi Arabia; however, early recognition of the disease is important for appropriate management and early referral for liver transplantation evaluation. The overall rate of liver transplantation in our cohort was 64.6% with an excellent five-year survival rate.

Liver Segment Disposition of Hepatocellular Carcinoma Predicts Microvascular Invasion.

Forlemu AN, Nana Sede Mbakop R, Bandaru P … +6 more , Gayam V, Moparty H, Sempokuya T, Pradhan F, Reddy M, Olivera M

Int J Hepatol · 2023 · PMID 37292454 · Full text

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survi... BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survival after tumor resection. AIM: This study evaluated the relation between MVI and HCC within various anatomical Couinaud's segments of the liver. METHOD: A multicenter retrospective review of HCC records was conducted from 2012 to 2017. HCC cases were identified using ICD-9 and 10 codes 155, C22.0, and C22.8. HCC patients who underwent liver transplants were included in this study. Liver segment of the location of HCC was obtained from radiographic records, and MVI information was obtained from pathology reports. Segmental distributions of HCC in MVI versus non-MVI groups were compared using Wilcoxon rank sum tests. value was set at <0.05. RESULTS: We analyzed 120 HCC patients who underwent liver transplantation. The mean age of our cohort was 57 years, and the most common etiology of liver disease was hepatitis C at 58.3%. The median HCC size was 3.1 cm, and MVI was present in 23.3% of the explanted specimens. MVI was 2 to 3 times significantly higher in patients with HCC affecting segments 2 and 3 and segments 4b and 5 ( = 0.01). Moreover, median survival was significantly lower in patients with MVI versus those without MVI (50 vs. 137 months, < 0.05). CONCLUSION: MVI was significantly higher in HCC tumors located in liver segments 2 and 3 and 4b and 5, and survival was lower in patients with MVI compared with those without.

Inhibition of Gluconeogenesis by Boldine in the Perfused Liver: Therapeutical Implication for Glycemic Control.

Silva LCL, de Souza GH, Pateis VO … +7 more , Ames-Sibin AP, Silva BP, Bracht L, Comar JF, Peralta RM, Bracht A, Sá-Nakanishi AB

Int J Hepatol · 2023 · PMID 37056327 · Full text

The alkaloid boldine occurs in the Chilean boldo tree (). It acts as a free radical scavenger and controls glycemia in diabetic rats. Various mechanisms have been proposed for this effect, including inhibited glucose abs... The alkaloid boldine occurs in the Chilean boldo tree (). It acts as a free radical scavenger and controls glycemia in diabetic rats. Various mechanisms have been proposed for this effect, including inhibited glucose absorption, stimulated insulin secretion, and increased expression of genes involved in glycemic control. Direct effects on glucose synthesis and degradation were not yet measured. To fill this gap, the present study is aimed at ensuring several metabolic pathways linked to glucose metabolism (e.g., gluconeogenesis) in the isolated perfused rat liver. In order to address mechanistic issues, energy transduction in isolated mitochondria and activities of gluconeogenic key enzymes in tissue preparations were also measured. Boldine diminished mitochondrial ROS generation, with no effect on energy transduction in isolated mitochondria. It inhibited, however, at least three enzymes of the gluconeogenic pathway, namely, phosphoenolpyruvate carboxykinase, fructose-bisphosphatase-1, and glucose 6-phosphatase, starting at concentrations below 50 M. Consistently, in the perfused liver, boldine decreased lactate-, alanine-, and fructose-driven gluconeogenesis with IC values of 71.9, 85.2, and 83.6 M, respectively. Conversely, the compound also increased glycolysis from glycogen-derived glucosyl units. The hepatic ATP content was not affected by boldine. It is proposed that the direct inhibition of hepatic gluconeogenesis by boldine, combined with the increase of glycolysis, could be an important event behind the diminished hyperglycemia observed in boldine-treated diabetic rats.

Gamma-Glutamyl Transferase: A Friend against Cholestatic Itch? A Retrospective Observational Data Analysis in Patients with Extrahepatic Cholestasis.

Haijer FW, Van Vliet CB, Brusse-Keizer MGJ … +3 more , Van der Palen JAM, Kerbert-Dreteler MJ, Kolkman JJ

Int J Hepatol · 2023 · PMID 36816714 · Full text

METHODS: We included 235 patients with chronic extrahepatic cholestasis due to pancreatic cancer, cholangiocarcinoma, or papillary carcinoma. RESULTS: GGT was significantly higher in patients without pruritus (median 967... METHODS: We included 235 patients with chronic extrahepatic cholestasis due to pancreatic cancer, cholangiocarcinoma, or papillary carcinoma. RESULTS: GGT was significantly higher in patients without pruritus (median 967, IQR 587-1571) compared to patients with pruritus (median 561 IQR 266-1084 IU/l) ( < 0.01). In contrast, median alkaline phosphatase (AP) was 491 U/L (IQR; 353-684) in patients with pruritus and was not significantly different from 518 U/L (IQR; 353-726) in patients without pruritus ( = 0.524). Direct bilirubin was significantly higher in patients with pruritus compared to patients without pruritus (168 mol/L (IQR; 95-256) vs. 120 mol/L (IQR; 56.75-185.5)) ( < 0.01). After correcting for the extent of cholestasis direct bilirubin, the negative association between GGT and pruritus remained significant and became stronger ( < 0.001). CONCLUSION: Serum GGT activity is inversely associated with the presence of cholestatic itch in patients with chronic extrahepatic cholestasis.

Liver Injury Patterns and Hepatic Toxicity among People Living with and without HIV and Attending Care in Urban Uganda.

Wekesa C, Parkes-Ratanshi R, Kirk GD … +1 more , Ocama P

Int J Hepatol · 2023 · PMID 36748010 · Full text

INTRODUCTION: The evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and o... INTRODUCTION: The evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and other diagnostic tests. METHODS: Among people living with and without HIV and attending care, we used the ratio to evaluate for liver injury patterns. Liver injury patterns were defined as cholestatic ( < 2), mixed ( = 2-5), and hepatocellular ( > 5). RESULTS: Overall, the proportions of participants with cholestatic liver injury, mixed liver injury, and hepatocellular liver injury were 55%, 34%, and 4%, respectively, with similar distribution when stratified by HIV status. Alcohol use among participants without HIV was associated with all patterns of liver injury (cholestatic liver injury (OR = 4.9 CI (1.0-24.2); = 0.054), mixed liver injury (OR = 5.3 CI (1.1-27.3); = 0.043), and hepatocellular liver injury (OR = 13.2 CI (1.0-167.3); = 0.046)). Increasing age was associated with cholestatic liver injury among participants with HIV (OR = 2.3 CI (1.0-5.3); = 0.038). Despite a high hepatitis B prevalence among participants with HIV, there was no association with liver injury. CONCLUSIONS: Liver injury is prevalent among both people living with and without HIV in care, and cholestatic liver injury is the most common pattern. Alcohol is associated with all patterns of liver injury and increasing age associated with cholestatic liver injury among people living without HIV and people living with HIV, respectively.
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