Prevalence of hepatitis C virus infection among men who have sex with men with human immunodeficiency virus-1 infection between 2010 and 2020 in Japan: A single-center retrospective cohort study.

INTRODUCTION: The high prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) is an important health issue. The purpose of this study is to investigate the actual prevalence of HCV infection among HIV-positive MSM in Japan. METHODS: This study is a single-center retrospective cohort study. We collected data of HIV-infected MSM who visited our hospital from January 2010 to December 2020, and evaluated HCV prevalence, course of HCV infection, and direct-acting antiviral (DAA) treatment efficacy in HIV-infected MSM. RESULTS: Overall, 1135 HIV-infected MSM had HCV antibody (Ab) tests during the observation period. The first anti-HCV Ab positive rate in HIV-infected MSM was 4% (45/1135), and the seroconversion rate of HCV antibody was 3.6% (39/1090). Treponema pallidum hemagglutination antigen positivity (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.9 to 10.5) and intravenous drug injection (OR, 19; 95% CI, 3.4 to 149) were identified as factors associated with HCV Ab positivity. Spontaneous elimination of HCV infection was observed in 17.9% (7/39) of patients. DAA treatment was performed in 43 cases, and the overall sustained virologic response 12 (SVR12) rate for DAA treatment was 93% (40/43). CONCLUSION: A high HCV infection rate among HIV-infected MSM was observed in Japan. The DAA treatment response rate in patients with HIV/HCV co-infection was the high response rate.

Hydrogens detected by subatomic resolution protein crystallography in a [NiFe] hydrogenase.

The enzyme hydrogenase reversibly converts dihydrogen to protons and electrons at a metal catalyst. The location of the abundant hydrogens is of key importance for understanding structure and function of the protein. However, in protein X-ray crystallography the detection of hydrogen atoms is one of the major problems, since they display only weak contributions to diffraction and the quality of the single crystals is often insufficient to obtain sub-ångström resolution. Here we report the crystal structure of a standard [NiFe] hydrogenase (∼91.3 kDa molecular mass) at 0.89 Å resolution. The strictly anoxically isolated hydrogenase has been obtained in a specific spectroscopic state, the active reduced Ni-R (subform Ni-R1) state. The high resolution, proper refinement strategy and careful modelling allow the positioning of a large part of the hydrogen atoms in the structure. This has led to the direct detection of the products of the heterolytic splitting of dihydrogen into a hydride (H(-)) bridging the Ni and Fe and a proton (H(+)) attached to the sulphur of a cysteine ligand. The Ni-H(-) and Fe-H(-) bond lengths are 1.58 Å and 1.78Å, respectively. Furthermore, we can assign the Fe-CO and Fe-CN(-) ligands at the active site, and can obtain the hydrogen-bond networks and the preferred proton transfer pathway in the hydrogenase. Our results demonstrate the precise comprehensive information available from ultra-high-resolution structures of proteins as an alternative to neutron diffraction and other methods such as NMR structural analysis.

MazF activation causes ACA sequence-independent and selective alterations in RNA levels in Escherichia coli.

Escherichia coli MazF is a toxin protein that cleaves RNA at ACA sequences. Its activation has been thought to cause growth inhibition, primarily through indiscriminate cleavage of RNA. To investigate responses following MazF activation, transcriptomic profiles of mazF-overexpressing and non-overexpressing E. coli K12 cells were compared. Analyses of differentially expressed genes demonstrated that the presence and the number of ACA trimers in RNA was unrelated to cellular RNA levels. Mapping differentially expressed genes onto the chromosome identified two chromosomal segments in which upregulated genes formed clusters, and these segments were absent in the chromosomes of E. coli strains other than K12. These results suggest that MazF regulates selective, rather than indiscriminate, categories of genes, and is involved in the regulation of horizontally acquired genes. We conclude that the primary role of MazF is not only cleaving RNA indiscriminately but also generating a specific cellular state.

Development of Hepatocellular Carcinoma During Nivolumab Treatment for Recurrent Non-Small Cell Lung Cancer: A Case Report.

Nivolumab, a monoclonal antibody targeting programmed cell death 1 (PD-1), is the standard second-line therapy for advanced non-small cell lung cancer (NSCLC). In the current immunotherapy era, it is often difficult to evaluate the therapeutic effect, disease progression, and pseudo-enlargement of the tumor or the emergence of another etiology. In the present report, we describe a 79-year-old patient with hepatocellular carcinoma (HCC) newly detected during nivolumab treatment for recurrent NSCLC. When the patient was 73 years old, he had suffered from NSCLC and received concurrent chemoradiotherapy comprising cisplatin and docetaxel, achieving a complete response. Six years after the chemoradiotherapy, the patient had multiple lung and hepatic lesions. We thus started the treatment with nivolumab for recurrent NSCLC. All those lesions responded to nivolumab over nine cycles. By contrast, a lesion was newly detected in the medial segment of left hepatic lobe, liver segment 4 (S4), and was gradually getting larger, as judged by computed tomographic scan. Liver biopsy revealed the growing lesion to be a well-differentiated HCC. Consequently, the patient was treated with radiofrequency ablation to HCC, while nivolumab treatment was continued for NSCLC. Immunohistochemical analysis of the HCC specimens revealed nuclear accumulation of ß-catenin compared with normal liver cells and undetectable expression of program death ligand 1 (PD-L1). Such expression profiles of ß-catenin and PD-L1 in HCC may be responsible for the resistance against nivolumab treatment. Immunohistochemical features of the biopsy specimens may be predictive of the effectiveness of the immunotherapy in HCC.

Cysteine SH and Glutamate COOH Contributions to [NiFe] Hydrogenase Proton Transfer Revealed by Highly Sensitive FTIR Spectroscopy.

A [NiFe] hydrogenase (H2 ase) is a proton-coupled electron transfer enzyme that catalyses reversible H2 oxidation; however, its fundamental proton transfer pathway remains unknown. Herein, we observed the protonation of Cys546-SH and Glu34-COOH near the Ni-Fe site with high-sensitivity infrared difference spectra by utilizing Ni-C-to-Ni-L and Ni-C-to-Ni-SIa photoconversions. Protonated Cys546-SH in the Ni-L state was verified by the observed SH stretching frequency (2505 cm-1 ), whereas Cys546 was deprotonated in the Ni-C and Ni-SIa states. Glu34-COOH was double H-bonded in the Ni-L state, as determined by the COOH stretching frequency (1700 cm-1 ), and single H-bonded in the Ni-C and Ni-SIa states. Additionally, a stretching mode of an ordered water molecule was observed in the Ni-L and Ni-C states. These results elucidate the organized proton transfer pathway during the catalytic reaction of a [NiFe] H2 ase, which is regulated by the H-bond network of Cys546, Glu34, and an ordered water molecule.

Redox Potential-Dependent Formation of an Unusual His-Trp Bond in Bilirubin Oxidase.

Bilirubin oxidase (BOD) belongs to the family of blue multicopper oxidases, and catalyzes the concomitant oxidation of bilirubin to biliverdin and the reduction of molecular oxygen to water via a four-electron reduction system. The active sites of BOD comprise four copper atoms; type I copper (T1Cu) forms a mononuclear site, and a cluster of three copper atoms forms a trinuclear center. In the present study, we determined the high-resolution crystal structures of BOD from the fungus Myrothecium verrucaria. We investigated wild-type (WT) BOD and a BOD mutant called Met467Gln, which is inactive against bilirubin. The structures revealed that a novel post-translational crosslink between Trp396 and His398 is formed in the vicinity of the T1Cu site in WT BOD, whereas it is absent in the Met467Gln mutant. Our structural and computational studies suggest that the His-Trp crosslink adjusts the redox potential of T1Cu to that of bilirubin to efficiently abstract electrons from the substrate.

Reduced therapeutic effect of antiviral drugs in patients with hepatitis B virus reactivation after hematopoietic stem cell transplantation.

AIM: Patients with resolved hepatitis B virus (HBV) infection following hematopoietic stem cell transplantation (HSCT) are potentially at high risk of HBV reactivation. Although antiviral drug therapy is recommended when HBV DNA reappears in the serum, drug efficacy after HBV reactivation remains unclear. METHODS: Host immune response against HBV was investigated by immunological analyses at 12 months after entecavir (ETV) treatment in six HSCT-treated and five non-HSCT-treated patients with HBV reactivation, and 18 patients with chronic hepatitis B (CHB). Peripheral HBV-specific CD8+ T cells were analyzed for total numbers by flow cytometry and tetramer staining, as was intracellular γ-interferon (IFN-γ) production and CD107a expression in response to HBV peptides. Interleukin-10 (IL-10)-expressing CD19+ B-cell count and serum inflammatory cytokine levels were also analyzed. RESULTS: Serum HBV DNA was detectable in HSCT-treated patients with HBV reactivation at 12 months compared with other groups, indicating insufficient ETV efficacy against HBV. The HBV-specific CD8+ T-cell counts in HSCT-treated patients with HBV reactivation were significantly lower compared with those in non-HSCT patients. Additionally, IFN-γ production and CD107a expression by CD8+ T cells after incubation with HBV peptides was significantly reduced in HSCT-treated compared with CHB patients at 12 months after ETV treatment. Conversely, HSCT-treated patient serum IL-10 levels were significantly elevated compared with those in non-HSCT patients. Finally, IL-10-producing CD19+ B-cell counts were increased in HSCT-treated compared with CHB patients. CONCLUSION: After HBV reactivation, ETV efficacy was impaired in HSCT-treated patients as evidenced by low HBV-specific CD8+ T-cell counts and high B-cell IL-10 production.

Tumor invasion to the arteries feeding the gallbladder as a novel risk factor for cholecystitis after metallic stent placement in distal malignant biliary obstruction.

BACKGROUND AND AIM: Cholecystitis is a major complication after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement. METHODS: Incidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016. RESULTS: Cholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow-up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57-137.18; P = 0.001) and 25.26 (95% CI, 4.12-154.98; P < 0.001), respectively. CONCLUSIONS: This study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement.

Wnt/ß-Catenin Signaling as a Potential Target for the Treatment of Liver Cirrhosis Using Antifibrotic Drugs.

Cirrhosis is a form of liver fibrosis resulting from chronic hepatitis and caused by various liver diseases, including viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, and autoimmune liver disease. Cirrhosis leads to various complications, resulting in poor prognoses; therefore, it is important to develop novel antifibrotic therapies to counter liver cirrhosis. Wnt/ß-catenin signaling is associated with the development of tissue fibrosis, making it a major therapeutic target for treating liver fibrosis. In this review, we present recent insights into the correlation between Wnt/ß-catenin signaling and liver fibrosis and discuss the antifibrotic effects of the cAMP-response element binding protein/ß-catenin inhibitor PRI-724.

Electrostatic roles in electron transfer from [NiFe] hydrogenase to cytochrome c3 from Desulfovibrio vulgaris Miyazaki F.

Electrostatic interactions between proteins are key factors that govern the association and reaction rate. We spectroscopically determine the second-order reaction rate constant (k) of electron transfer from [NiFe] hydrogenase (H2ase) to cytochrome (cyt) c3 at various ionic strengths (I). The k value decreases with I. To analyze the results, we develop a semi-analytical formula for I dependence of k based on the assumptions that molecules are spherical and the reaction proceeds via a transition state. Fitting of the formula to the experimental data reveals that the interaction occurs in limited regions with opposite charges and with radii much smaller than those estimated from crystal structures. This suggests that local charges in H2ase and cyt c3 play important roles in the reaction. Although the crystallographic data indicate a positive electrostatic potential over almost the entire surface of the proteins, there exists a small region with negative potential on H2ase at which the electron transfer from H2ase to cyt c3 may occur. This local negative potential region is identical to the hypothetical interaction sphere predicted by the analysis. Furthermore, I dependence of k is predicted by the Adaptive Poisson-Boltzmann Solver considering all charges of the amino acids in the proteins and the configuration of H2ase/cyt c3 complex. The calculation reproduces the experimental results except at extremely low I. These results indicate that the stabilization derived from the local electrostatic interaction in the H2ase/cyt c3 complex overcomes the destabilization derived from the electrostatic repulsion of the overall positive charge of both proteins.

Improved Exercise Capacity After Cardiac Rehabilitation Is Associated with Reduced Visceral Fat in Patients with Chronic Heart Failure.

Participation in a comprehensive cardiac rehabilitation (CR) program has been shown to reduce mortality and improve exercise capacity and symptoms in patients with chronic heart failure (CHF). Reduced exercise capacity leads to a concomitant reduction of skeletal muscle mass and accumulation of body fat. However, it is currently unknown whether CR reduces visceral adipose tissue (VAT) and/or subcutaneous abdominal adipose tissue (SAT) in patients with CHF. In addition, the body composition associated with improved exercise capacity after CR in patients with CHF has not been previously studied. Nineteen CHF patients who were categorized as NYHA functional class II or III and had received optimal medical treatment including a CR program for 5 months were enrolled in this study. The CR program significantly increased peak VO2 and reduced B-type natriuretic peptide. In addition, fat and body composition analysis showed reductions in the visceral fat tissue (VAT) area, subcutaneous abdominal adipose tissue (SAT) area, body weight, and total fat weight after CR. There were no changes in total water weight and total muscle weight. Single regression analysis revealed that the amelioration of reduced exercise capacity seen after CR is associated with reduced VAT area but not with SAT area or body weight. In conclusion, CR reduces VAT and improves exercise capacity in patients with CHF. This suggests that reducing VAT is important for CR to be most effective in the treatment of CHF.

Photoactivation of the Ni-SIr state to the Ni-SIa state in [NiFe] hydrogenase: FT-IR study on the light reactivity of the ready Ni-SIr state and as-isolated enzyme revisited.

The Ni-SIr state of [NiFe] hydrogenase from Desulfovibrio vulgaris Miyazaki F was photoactivated to its Ni-SIa state by Ar(+) laser irradiation at 514.5 nm, whereas the Ni-SL state was light induced from a newly identified state, which was less active than any other identified state and existed in the "as-isolated" enzyme.

Comparison between bougies and stylets for simulated tracheal intubation with the C-MAC D-blade videolaryngoscope.

BACKGROUND: The C-MAC D-blade is a new, highly angulated, videolaryngoscope blade designed for use in patients with difficult airways. Directing a tracheal tube into the trachea with any indirect viewing laryngoscope can be difficult, even with a good view of the laryngeal inlet. OBJECTIVE: To determine which introducing strategy is most suitable for use with the C-MAC D-blade videolaryngoscope. DESIGN: Observational manikin study. SETTING: Centre for Simulation and Patient Safety. PARTICIPANTS: Twenty-four anaesthetists of at least 12 months' of experience. INTERVENTIONS: Six tracheal tube introducer strategies (no tracheal tube introducer (TX); hockey stick stylet (SH); Gliderite stylet (SG); bougie with tube loaded distally, near its curved tip (BD); bougie with tube loaded proximally (BP); bougie unloaded until tracheal placement (BU)) for each of two laryngoscopy settings (easy and difficult) in a SimMan 3G manikin. Two intubation attempts, with a maximum time allowance of 60 s each, were allowed for all laryngoscopy setting/introducer combinations. MAIN OUTCOME MEASURES: Time to intubate in seconds. Secondary outcome was overall subjective difficulty using a visual analogue scale. RESULTS: In the easy laryngoscopy setting, time to intubation was [median (interquartile range): SH 8.5 sec (7 to 11); SG 10 (8 to 11.5); BD 11 (10 to 12.5); TX 11 (7 to 31.5); BP 12 (11 to 13.5); BU 13 (11 to 14.5). There was no evidence of an overall difference in introducer strategies for time to intubate (P <  .025) with SG and SH found to be favourable when compared with BU, and SH was also favourable when compared with BP. In the difficult laryngoscopy setting, time to intubation was: SG 11.5 (10 to 17.5); SH 14 (12 to 22); BD 15.5 (12 to 23.5); BU 16.5 (14 to 21); BP 16.5 (15.5 to 20.5); TX 60 (26.5 to 60). There was evidence of an overall difference in introducer strategies for time to intubate (P < 0.025) with all introducers found to be favourable compared with TX. SG was found to be favourable when compared with BU and BP. In groups TX and SH, anaesthetists failed to intubate in 13 of 24 cases and 1 of 24 cases, respectively. The visual analogue scores tended to reflect intubation times, more so in the difficult setting. CONCLUSION: The differences in time to intubate in both the easy and difficult laryngoscopy settings were minor for the different introducer strategies studied. The stylet introducers tended to take less time, but this did not result in important statistical differences. When using the C-MAC D-blade videolaryngoscope for simulated tracheal intubation, stylets and bougies performed in a similar fashion.

Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.

Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ΔACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.

Cardiac rehabilitation reduces serum levels of oxidized low-density lipoprotein.

BACKGROUND: Oxidized low-density lipoprotein (oxLDL) levels have been found to play an important role in the progression of atherosclerosis. However, methods for effectively reducing oxLDL levels have not been established. Comprehensive cardiac rehabilitation (CR) with exercise training prevents the progression of atherosclerosis, and might reduce oxLDL levels. METHODS AND RESULTS: We measured the serum levels of malondialdehyde-modified LDL (MDA-LDL), a marker of oxLDL, in 136 patients who were enrolled in a 6-month CR program. Peak oxygen consumption (V̇O2) and MDA-LDL levels were analyzed, before and 6 months after enrolment. In total, 67 patients completed the CR program (CR group) and 69 patients failed to complete the program (non-CR group). Peak V̇O2increased significantly in the CR group (P<0.01). The levels of MDA-LDL decreased significantly in the CR group (P<0.01) but not in the non-CR group. ∆V̇O2(peak V̇O2after CR-peak V̇O2before CR) was negatively associated with ∆MDA-LDL (MDA-LDL after CR-MDA-LDL before CR) (R(2)=0.11, P=0.01). Multiple regression analysis showed that continuing CR was an independent determining factor for lowering MDA-LDL levels. CONCLUSIONS: CR decreases oxLDL levels in patients with cardiovascular diseases. Moreover, CR may prevent cardiovascular events through an antioxidative effect.

Control of the transition between Ni-C and Ni-SI(a) states by the redox state of the proximal Fe-S cluster in the catalytic cycle of [NiFe] hydrogenase.

[NiFe] hydrogenase catalyzes the reversible cleavage of H2. The electrons produced by the H2 cleavage pass through three Fe-S clusters in [NiFe] hydrogenase to its redox partner. It has been reported that the Ni-SI(a), Ni-C, and Ni-R states of [NiFe] hydrogenase are involved in the catalytic cycle, although the mechanism and regulation of the transition between the Ni-C and Ni-SI(a) states remain unrevealed. In this study, the FT-IR spectra under light irradiation at 138-198 K show that the Ni-L state of [NiFe] hydrogenase is an intermediate between the transition of the Ni-C and Ni-SI(a) states. The transition of the Ni-C state to the Ni-SI(a) state occurred when the proximal [Fe4S4]p(2+/+) cluster was oxidized, but not when it was reduced. These results show that the catalytic cycle of [NiFe] hydrogenase is controlled by the redox state of its [Fe4S4]p(2+/+) cluster, which may function as a gate for the electron flow from the NiFe active site to the redox partner.

Stem Cell Growth Factor-ß as a Predictive Biomarker of Response to Chemotherapy and Prognosis in Patients with Advanced-Stage Hepatocellular Carcinoma: A Retrospective Study.

In this retrospective study, we investigated the potential application of serum stem cell growth factor beta (SCGF-ß) as a biomarker for predicting the therapeutic response and prognosis in patients with hepatocellular carcinoma (HCC) undergoing atezolizumab and bevacizumab (Atz/Bev) combination therapy. Pre- and post-treatment serum SCGF-ß levels were measured and analyzed in relation to treatment outcomes and overall survival (OS). Pretreatment SCGF-ß levels were associated with treatment response. Patients with SCGF-ß levels exceeding the 163,295 pg/mL cutoff experienced significantly reduced OS, with a median OS of 12.03 months, compared to 28.87 months in those with SCGF-ß levels at or below this threshold. These findings suggest that SCGF-ß can serve as a predictive marker for clinical outcomes in HCC treatment, highlighting the need for prospective studies to further validate these results and clarify the mechanisms underlying SCGF-ß-related therapeutic resistance.

Effectiveness of Chemotherapy on Long-Term Survival in a Case of Advanced Juvenile Hepatocellular Carcinoma Without Viral Hepatitis Infection.

Hepatocellular carcinoma (HCC) usually occurs in settings of cirrhosis and chronic hepatitis B or C virus (HBV and HCV, respectively) infection; it is extremely rare in patients <40 years of age since viral- or alcohol-induced chronic hepatitis develops over a prolonged period. Juvenile HCC is mostly associated with persistent HBV infection; cases unrelated to HBV or HCV infection (non-B, non-C juvenile HCC) are sporadic and treated in the same way as classical HCC. A woman in her late 30s was diagnosed with HCC in a healthy liver; her imaging findings were typical of HCC with bone metastasis. She was administered a combination of tyrosine kinase inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors. Throughout chemotherapy, the liver reserve was Grade A on the Child-Pugh classification and tumor markers remained under control without marked elevation. Our patient is the first reported long-term survivor of unresectable non-B, non-C juvenile HCC following chemotherapeutic treatment.

A Case of Nonagenarian Gastric Anisakiasis with Atypical Presentation.

Introduction: Anisakiasis is a parasitic disease caused by larvae from anisakid nematodes. In recent years, there has been an increase in cases of anisakiasis, a relatively uncommon medical condition. Case Presentation: A 93-year-old woman with chronic heart failure developed hives and nausea 6 h after eating silver flounder sashimi, leading to suspicion of fish allergy. Despite treatment, symptoms persisted and progressed to abdominal pain. An upper gastrointestinal endoscopy revealed an Anisakis larva in her stomach, an unusual finding given her age. After endoscopic removal of the living worm, the patient's symptoms were relieved. Conclusion: A case of atypical anisakiasis in a 93-year-old patient was demonstrated. This case underscores the importance of considering atypical presentations in clinical decision-making.

Alpha-fetoprotein-producing gastric cancer with ruptured liver metastasis mimicking hepatocellular carcinoma.

Alpha-fetoprotein (AFP)-producing gastric cancer is a rare subtype of gastric cancer known for its aggressive nature. We present an uncommon case of a 60s male with multiple liver tumors, initially suggested as hepatocellular carcinoma (HCC) by imaging. However, a subsequent gastric biopsy revealed a poorly differentiated adenocarcinoma with hepatoid features, and liver biopsy mirrored these findings. The disease progressed swiftly, with the patient representing owing to the spontaneous rupture of a metastatic liver tumor, an extremely rare occurrence, especially in metastatic liver cancers. Such ruptures in AFP-producing gastric cancer may be attributed to the tumor's rich blood flow. Distinctly differentiating this subtype from HCC is pivotal for apt management, as was evident in our case. The diagnosis was particularly challenging due to the similarities in imaging presentations between AFP-producing gastric cancer liver metastasis and HCC. This case underscores the need for vigilant diagnosis, emphasizing the importance of liver biopsy, especially in the absence of chronic liver disease. It also highlights the potential complications, like spontaneous rupture, associated with this rare form of gastric cancer.