Assessment of hepatic functional reserve is critically important for preventing serious complications after hepatectomy such as liver failure. While the indocyanine green clearance test (ICG) is a liver-specific test that is not affected by other organs and is commonly used to evaluate liver reserve capacity. We lack knowledge regarding what test should be performed for patients with jaundice, portal shunts, or intolerance whose liver function cannot be accurately assessed by ICG. To close this gap, we focused on changes in amino acid metabolism associated with impaired liver function. The branched-chain amino acid-to-tyrosine ratio (BTR) reflects the severity of liver disease. The research objectives are to evaluate whether BTR is useful as an alternative test to ICG. The primary endpoint of this study is to clarify the correlation between BTR and ICG. The secondary endpoints are to provide pathological confirmation of liver fibrosis and clarify the relationship with short- and long-term outcome and to examine whether it is clinically significant as a marker of preoperative liver reserve capacity. This retrospective single-center cohort study included patients who underwent hepatectomy for HCC between January 2011 and December 2016. In this study, 235 patients were enrolled, with a median BTR of 5.58. The BTR and indocyanine green stagnation rates at 15 min (ICG-R15) showed a significant correlation (r = -0.57, p < 0.001), whereas 1/BTR showed an even stronger correlation (r = 0.66, p < 0.0001). Conversion formulas that is a regression equation predicting ICG test results with BTR as an explanatory variable were analyzed. In addition to its correlation with ICG-R15, BTR was significantly associated with liver fibrosis in the background liver pathology of resected specimens, demonstrating higher sensitivity for detecting cirrhosis compared to ICG. The high BTR group exhibited significantly longer survival than the low BTR group (p = 0.020). The results indicate that BTR and ICG are significantly correlated. Comparable to ICG, BTR is a predictor of liver fibrosis and a prognostic factor for postoperative outcomes in patients with HCC. Although 99mTc-GSA scintigraphy has been reported to correlate with IGC, the correlation coefficient and number of cases in this study are equivalent. BTR can be tested through routine blood sampling. The results of this study demonstrate the potential for clinically evaluating preoperative hepatic reserve capacity in a less invasive, more cost-effective without facility limitations.

Hepatolithiasis, the presence of calculi within the intrahepatic bile ducts, is a rare but challenging condition that can lead to complications such as cholangitis and liver dysfunction. We present the case of a 65-year-old male patient who presented with a history of abdominal pain and chills without clinical jaundice or fever. Laboratory tests revealed mild abnormalities in liver function tests with a cholestatic pattern. Magnetic resonance cholangiopancreatography (MRCP) revealed cholelithiasis, choledocholithiasis, and hepatolithiasis in segments V and VIII. He was started on antibiotic therapy with ciprofloxacin, and an ERCP and cholangioscopy were performed for the extraction of the choledocholithiasis. During the procedure, a stenosis of the right hepatic duct was found and biopsied. In addition, papillotomy was performed with the extraction of multiple stones and biliary sludge, and a 10 Fr plastic stent was placed in the right duct. The biopsy result revealed inflammatory tissue, with neoplasia not completely excluded. An elective laparoscopic right hepatectomy was scheduled. During surgery, ultrasound and cholangiography revealed the presence of hepatolithiasis in segment 4, prompting the decision to change the surgical technique to an extended right hepatectomy, which was performed entirely laparoscopically without incidents. Histopathological analysis of the biliary margin confirmed the absence of malignancy. Totally laparoscopic extended right hepatectomy is a feasible and effective treatment for hepatolithiasis, providing good outcomes with minimal morbidity. This case underscores the importance of surgical intervention in managing complex hepatobiliary disorders.

Objective: To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods: The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results: Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g, all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion: AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

A 42-year-old male presented with a two-month history of right upper quadrant abdominal pain, worsening over four days. Six months earlier, he had undergone a laparoscopic cholecystectomy. Examination revealed no jaundice or tenderness, and liver function tests were normal. The patient's basic inflammatory markers were within the normal range. Ultrasound revealed a residual gallbladder stump or dilated cystic duct with a calculus, and magnetic resonance cholangiopancreatography (MRCP) demonstrated a 3 × 1 cm stump with an 8 mm hypointense focus. Endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessful due to distorted anatomy. Surgical exploration confirmed a cystic duct remnant containing sludge and concretions, which was excised completely. Postoperative recovery was uneventful, and histopathology revealed chronic inflammatory changes consistent with cystic duct stump pathology. This case illustrates that residual gallbladder stump cholelithiasis may occur after laparoscopic cholecystectomy. Recognition of this possibility, along with appropriate imaging, enables timely diagnosis. Surgical excision of the cystic duct remnant provides definitive treatment and effective symptom relief in patients with post-cholecystectomy syndrome caused by residual ductal concretions.

Obstructive jaundice (OJ)-induced kidney injury has a high mortality rate, severely affecting patient prognosis. Gpbar1, a bile acid receptor, plays a key role in maintaining tissue homeostasis in organs such as the liver and pancreas during OJ. However, its role in obstructive jaundice-induced kidney injury remains unexplored. This study investigated the protective role of Gpbar1 in OJ-induced kidney injury. Sprague-Dawley rats underwent common bile duct ligation to establish an OJ model. Organ damage was evaluated by pathological examination, TUNEL staining, and liver/kidney function tests to assess both OJ model establishment and kidney injury. Mitochondrial function changes were assessed through electron microscopy, SOD, MDA, GSH and ATP detection. Immunohistochemistry and Western blot were used to assess Gpbar1, SIRT1, and PGC-1α expression. HK-2 cells were treated with deoxycholic acid to establish a renal tubular epithelial cell injury model. Lentiviral vectors were used to overexpress or knock down Gpbar1, combined with interventions using SIRT1 and PGC-1α agonists and inhibitors. The Gpbar1-SIRT1-PGC-1α axis was validated by qRT-PCR and WB. The protective role of the Gpbar1-SIRT1-PGC-1α axis in OJ-induced kidney injury was studied using CCK-8, transmission electron microscopy, ROS detection, and mitochondrial membrane potential assays. In the rat OJ model, the model group exhibited injury-related pathological changes compared to control group. Liver and kidney function markers and TUNEL-positive cells significantly increased, and structural and functional damage in the kidneys occurred. Mitochondrial structural disorder occurred in the kidneys, with significant reductions in SOD, GSH, and ATP levels, while MDA levels were significantly increased, indicating impaired antioxidant capacity and energy metabolism dysfunction. IHC, WB, and qRT-PCR revealed that protein and mRNA levels of Gpbar1, SIRT1, and PGC-1α in kidney tissues were lower in the model group. In the cellular model, DCA treatment and Gpbar1 knockdown significantly reduced cell viability, caused mitochondrial structural disorder, increased ROS levels and decreased JC-1 ratio, while Gpbar1 overexpression reversed these changes. After treatment with the SIRT1 inhibitor EX527, PGC-1α expression significantly decreased. We used SIRT1 inhibitors, activators and PGC-1α inhibitors to conduct positive and negative regulation experiments and confirmed the hierarchical regulatory effect of Gpbar1 on SIRT1-PGC-1α. Gpbar1 influences oxidative stress resistance via the SIRT1-PGC-1α axis, promotes mitochondrial functional homeostasis, and alleviates kidney injury induced by obstructive jaundice.

Patients with liver diseases, such as liver cirrhosis and liver failure, have a high likelihood of developing hepatic encephalopathy (HE). HE is characterised by neurological impairments ranging from mild cognitive dysfunction to severe coma. Hyperammonaemia, metabolic disruption, and inflammation are recognised as key factors in the onset of HE. Recently, impaired autophagy has also been suggested to contribute to the development of HE. Therefore, in this study, we aimed to examine whether the autophagy inducer torin-1 is effective in reducing signs of HE. In this study, C57BL/6 mice were subjected to bile duct ligation (BDL) for 14 days to establish a model of HE. Liver function and structure were assessed using aspartate aminotransferase, alanine aminotransferase, total bilirubin, and haematoxylin and eosin staining, respectively. Neurological function was evaluated through the elevated plus maze, novel object recognition test, marble-burying test, clasping test, and passive avoidance test. To evaluate the effects of torin-1, it was administrated intraperitoneally to mice daily for 14 days. Changes in autophagy, cholesterol metabolism, and the cytokine/chemokine profile in the cerebral cortex were measured with and without torin-1 treatment. We found that although systemic administration of torin-1 could not reduce the induction of jaundice and liver impairment caused by BDL, it appeared to delay the onset of HE. Torin-1 treatment reduced the BDL-induced elevation in serum cholesterol and ammonia levels. Furthermore, abnormal expression of autophagy- and cholesterol-associated molecules in the cerebral cortex was reduced by torin-1 treatment. Cognitive function was improved in mice undergoing BDL with torin-1 treatment. Conclusively, these findings indicate that the induction of autophagy was found to alleviate the adverse effects seen in HE by regulating cholesterol metabolism in the cerebral cortex. The autophagy inducer torin-1 might be a potential approach to alleviate alterations and symptoms in HE.

Hepatic sinusoidal obstruction syndrome (HSOS) is often caused by the ingestion of pyrrolizidine alkaloids (PAs). To date, research on PAs-induced HSOS remains limited. Due to differing etiologies of HSOS in Western and Eastern populations, the clinical features, imaging findings, treatment approaches, and outcomes of HSOS caused by hematopoietic stem cell transplantation or oxaliplatin may not be directly applicable to PAs-induced HSOS. PAs-induced HSOS commonly presents with painful hepatomegaly, ascites, and jaundice. Laboratory tests commonly show abnormal liver function in patients with PA-induced HSOS. Contrast-enhanced computed tomography and magnetic resonance imaging often reveal distinctive imaging features and significant histopathological liver changes in PAs-induced HSOS. These findings highlight the effectiveness of radiological imaging and liver biopsy as diagnostic tools. Treatment strategies for PAs-induced HSOS include fluid management, anticoagulation therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation. However, managing PAs-induced HSOS remains challenging. This paper presents the case of an elderly male diagnosed with gastric cancer complicated by hepatic sinusoidal obstruction syndrome. The diagnosis was based on characteristic imaging findings, a history of pyrrolizidine alkaloids ingestion, and standard diagnostic criteria, including liver biopsy and histological examination. The patient recovered fully after timely diagnosis and treatment, which included radical total gastrectomy, hepatoprotective diuretics, albumin supplementation, and low-molecular-weight heparin therapy.

BACKGROUND Acute fatty liver of pregnancy (AFLP) is a rare and catastrophic disease in pregnancy. It is important to distinguish between pathogenic diseases that cause abnormal liver function tests during pregnancy and typical physiological changes. An AFLP diagnosis can be established using Swansea criteria. AFLP typically occurs in the third trimester of pregnancy or postpartum, with a median presentation of 35-37 weeks of pregnancy. AFLP is also an obstetrical and medical emergency that is characterized by rapid deterioration of the patient's condition. CASE REPORT We present 3 cases from a tertiary hospital in Indonesia. The Swansea criteria were met in all 3 cases. Our cases were specifically characterized by complaints of fever. Fever complaints were not included in the Swansea criteria. The complaint of fever served to deceive and disorient the first treating clinician, resulting in a late referral. Delay of referral can lead to inappropriate treatment, prolonged duration of recovery, and the emergence of various complications, even death. In all of the cases reported here, the patients experienced detrimental effects and outcomes of the maternal and fetal condition. This case report also confirms that fever was the main symptom experienced by the patients who were hospitalized. Other common initial symptoms were nausea, vomiting, jaundice, and encephalopathy. CONCLUSIONS We propose that fever complaints be considered as criteria for AFLP diagnosis in Indonesia. However, more research is still needed with a larger number of cases. Prompt and appropriate treatment will result in a significantly more favorable outcome. Prompt identification, early diagnosis, immediate delivery, and comprehensive supportive treatment are important for maternal and infant outcomes in patients with AFLP.