An assessment of risk factors for recurrence and survival for patients undergoing liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with increasing rates of incidence and mortality. Surgical resection is curative for patients who are diagnosed at early stages of iCCA. Limited data exist regarding risk factors for postresection recurrence and overall survival as iCCA is rare, and majority of patients are diagnosed at an advanced stage and thus not candidates for resection. We aimed to analyze clinical and laboratory characteristics, tumor histology, locoregional invasion, recurrence and survival in patients undergoing curative resection for iCCA. METHODS: All patients who underwent curative resection for iCCA between 2006 and 2023 at our institution were included in the study. Clinical characteristics, laboratory, histological and follow-up data were collected. RESULTS: The 1-, 3-, and, 5-year survival rates were 90.9%, 65.9% and 44.2%, respectively. About 65.6% of patients had recurrence in a median of 1.2 years after liver resection. Positive surgical margins were present in 20.73% of patients. Notably, 80.51% had solitary tumor and the remaining 19.48% had multifocal tumor. A total of 64.51% of patients received adjuvant chemotherapy after resection. A total of 26 (31.3%) patients had died during the follow-up period. Duration from liver resection to last follow-up or death was 1.6 years (0.8-3.2). Overall median survival was 4.6 years. The presence of lymph node metastases, vascular invasion, positive surgical margin and advanced tumor stage at diagnosis were associated with significantly worse overall survival, which remained significant in multivariable model for advanced tumor stage and positive surgical margin. CONCLUSION: Despite curative resection, recurrence rate is high and overall survival is poor in patients with iCCA. Real-world data regarding patient characteristics and longitudinal follow-up remain important as iCCA is a rare malignancy.

Approach to Liver Transplantation: Is There a Difference between East and West?

Liver transplantation (LT) remains the only curative treatment for end-stage liver disease as well as acute liver failure. With the exponential increase in organ demand due to the increasing incidence and prevalence of liver diseases, the need to overcome the supply and demand mismatch has arisen. In this review, we discuss the current universal status of LT, emphasizing various LT practices worldwide.

Ischemic heart disease mortality in individuals with inflammatory bowel disease: A nationwide analysis of disparities in the United States.

INTRODUCTION: Inflammatory bowel disease (IBD) is linked to immune-mediated pathogenesis and a pro-inflammatory state, leading to accelerated atherosclerosis. This earlier onset of clinical cardiovascular disease poses significant morbidity and mortality. We sought to identify IHD mortality trends in individuals with IBD in the United States (US). METHODS: Mortality due to ischemic heart diseases (IHD) as the underlying cause of death with the IBD as a contributor of death were queried from death certificates using the CDC database from 1999 to 2020. Yearly crude mortality rates (CMR) were estimated by dividing the death count by the respective population size, reported per 100,000 persons. Mortality rates were adjusted for age using the Direct method and compared by demographic subpopulations. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality. RESULTS: Age-adjusted mortality rates (AAMR) decreased from 0.11 in 1999 to 0.07 in 2020, primarily between 1999 and 2018 (APC -4.41, p < 0.001). AAMR was higher among male (AAMR 0.08) and White (AAMR 0.08) populations compared to female populations (AAMR 0.06) and Black (AAMR 0.04) populations, respectively. No significant differences were seen when comparing mortality between urban (AAMR 0.07) and rural (AAMR 0.08) regions. Southern US regions (AAMR 0.06) had the lowest mortality rates when compared to the other US census regions: Northeastern (AAMR 0.08), Midwestern (AAMR 0.08), and Western (AAMR 0.08). CONCLUSION: Disparities in IHD mortality exist among individuals with IBD in the US based on demographic factors, with an overall decline in mortality during the 22-year period. Further investigation is warranted to confirm these findings and evaluate for contributors to the observed disparities.

Tropheryma whipplei Endocarditis Presenting as Valvulopathy and Multiple Septic Emboli.

A 63-year-old man was admitted to the hospital for nausea, vomiting, and right flank pain. He was found to have septic emboli in multiple organs secondary to aortic valve endocarditis. He was started on broad-spectrum antibiotics and underwent valve replacement. Blood cultures from admission were negative, but a blood polymerase chain reaction (PCR) test for fastidious difficult-to-culture pathogens showed a positive result for Tropheryma whipplei. Valve histopathological evaluation confirmed Tropheryma whipplei endocarditis. He was treated with intravenous penicillin followed by oral trimethoprim-sulfamethoxazole. A high index of suspicion for causes of culture-negative endocarditis needs to be maintained when blood cultures are negative despite clear evidence of endocarditis especially with large vegetation sizes and other complications such as septic emboli. Multiple imaging modalities are available to assist with diagnosis including transthoracic and transesophageal echocardiogram as well as cardiac computed tomography. A blood PCR test can identify the implicated pathogen in a more expeditious manner compared to valve histopathological evaluation. Treatment is complex and usually requires surgical intervention and prolonged antimicrobial therapy.

IgG4-related disease presenting with acute kidney injury and tubulointerstitial nephritis.

Immunoglobulin G-4 related disease (IgG4-RD) is an immune-mediated, inflammatory disease that often involves multiple organ systems. IgG4-RD can be classified according to the organs involved. Type 1 IgG4-RD is related to acute pancreatitis and sclerosing cholangitis. Disease manifestation is also seen in the retroperitoneal region, pelvic organs, and orbital space. Here we describe a rare case of IgG4-RD causing isolated acute kidney injury.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deletion in myeloid cells augments cholestatic liver injury.

Ductular reactive (DR) cells exacerbate cholestatic liver injury and fibrosis. Herein, we posit that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) emanates from recruited macrophages and restrains DR cell expansion, thereby limiting cholestatic liver injury. Wild type (WT), Trailfl/fl and myeloid-specific Trail deleted (TrailΔmye) C57BL/6 mice were exposed to DDC diet-induced cholestatic liver injury, which induced hepatomegaly and liver injury as compared to control diet-fed mice. However, parameters of liver injury, fibrosis, and inflammation were all increased in the TrailΔmye mice as compared to the WT and Trailfl/fl mice. High dimensional mass cytometry indicated that cholestasis resulted in increased hepatic recruitment of subsets of macrophages and neutrophils in the TrailΔmye mice. Spatial transcriptomics analysis revealed that the PanCK+ cholangiocytes from TrailΔmye mice had increased expression of the known myeloid attractants S100a8, Cxcl5, Cx3cl1, and Cxcl1. Additionally, in situ hybridization of Cxcl1, a potent neutrophil chemoattractant, demonstrated an increased expression in CK19+ cholangiocytes of TrailΔmye mice. Collectively, these data suggest that TRAIL from myeloid cells, particularly macrophages, restrains a subset of DR cells (i.e., Cxcl1 positive cells), limiting liver inflammation and fibrosis. Reprogramming macrophages to express TRAIL may be salutary in cholestasis.

Diagnostic Performance of the ICD-10 Code K76.82 for Hepatic Encephalopathy in Patients With Cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is prevalent and is associated with increased morbidity and mortality among patients with cirrhosis. On October 1, 2022, a new, specific International Classification of Diseases-10 code for HE, K76.82, was introduced. We aimed to analyze the diagnostic accuracy of K76.82. METHODS: Diagnostic performance of K76.82 for HE (sensitivity, specificity, positive predictive ratio, and negative predictive ratio) was evaluated in 2 large health systems compared with lactulose, rifaximin, and K72.90. RESULTS: A total of 2,483 patients were analyzed. The combination term "lactulose or rifaximin" showed the highest sensitivity of >98% while K76.82 demonstrated a specificity of >87% in all cohorts. DISCUSSION: Although K76.82 is promising, the combination term "lactulose or rifaximin" identified patients with HE more accurately.

Presence of Portomesenteric Venous Gas and Pneumatosis Intestinalis in Nonocclusive Mesenteric Ischemia as a Complication of Transrectal Ultrasound-Guided Prostate Biopsy.

A 58-year-old man with a history of mechanical aortic valve replacement, on anticoagulation with warfarin, presented to the emergency department with hematochezia 1 day after undergoing transrectal ultrasound-guided prostate biopsy. On presentation, he was found to have hemorrhagic shock. Fluid resuscitation, packed red blood cell transfusion, and empiric antibiotic therapy were initiated, and the patient was admitted to an intensive care unit. Abdominal-pelvic computed tomography demonstrated portomesenteric venous gas and pneumatosis intestinalis. Colonoscopy showed ischemic ulcers at the ascending colon and stigmata of recent bleeding at the site of biopsy in the rectum, which was treated endoscopically. The patient was discharged after continued improvement during hospitalization. On follow-up, the patient continued to be symptom-free, and a repeat colonoscopy demonstrated healing colonic ulcers.

A Comprehensive Review of the Diagnosis and Management of Acute Liver Failure.

Acute liver failure (ALF) is a rare and specific form of severe hepatic dysfunction characterized by coagulopathy and hepatic encephalopathy in a patient with no known liver disease. ALF carries a high morbidity and mortality. Careful attention should be given to hemodynamics and metabolic parameters along with the active surveillance of infections. Timely transfer and supportive management are important in an intensive care unit in a liver transplant center. Identifying patients who will and will not improve with medical management and may need emergent liver transplantation is critical. In this review, we provide a comprehensive update on the etiology, diagnosis, and management of ALF.

Unexpected cause of Kounis syndrome: hypersensitivity reaction to omeprazole.

Kounis syndrome is a rare type of acute coronary syndrome (ACS) that occurs as a result of an allergic or anaphylactic reaction. Kounis syndrome can be induced by various medications including antibiotics, proton pump inhibitors, antihypertensive medications, corticosteroids, and antineoplastic medications. Additionally, cases of Kounis syndrome associated with lansoprazole and pantoprazole have been previously reported in the literature. In this report, we present a case of Kounis syndrome associated with omeprazole use, and discuss the need for a high index of suspicion as it is often underrecognised.

Clinical presentation of peritoneal tuberculosis.

Peritoneal tuberculosis arises from hematogenous spread of pulmonary foci or from direct spread from an adjacent structure. Diagnosis of peritoneal tuberculosis can be challenging due to nonspecific symptoms, insidious onset, and variable imaging findings. Herein, we report a patient presenting with ascites who was eventually diagnosed with peritoneal tuberculosis.

Histologic and Clinical Outcomes of Patients Developing Post-Liver Transplant Plasma Cell-Rich Rejection.

OBJECTIVES: Plasma cell-rich rejection (PCCR), also known as "plasma cell hepatitis" or "de novo autoimmune hepatitis," is a cause of allograft dysfunction occurring post-liver transplantation (LT). Patients often develop allograft failure and may require repeat LT. PCRR may fall within the spectrum of different histologies associated with antibody-mediated rejection (AMR), which is associated with donor-specific antibodies (DSAs) and positive complement component C4 (C4d) immunostaining. We sought to analyze the histologic and clinical outcomes of patients having biopsy-proven PCRR as well as to examine its C4d staining and DSA profiles. METHODS: We identified patients having PCRR between 2000 and 2020 using the electronic pathology database at our institution. We included patients who underwent at least one follow-up liver biopsy after establishing the PCRR diagnosis to assess future histologic progression and outcomes. Mean fluorescence intensity for at least one single DSA of 2,000 or higher was considered positive. Histologic diagnosis of PCRR was independently made by an experienced liver pathologist. RESULTS: A total of 35 patients were included in the study. Hepatitis C virus was the most common etiology for LT (59.5%). Mean ± SD age at LT was 49.0 ± 12.7 years. Forty percent of patients developed PCRR within 2 years of LT. Most patients (68.5%) had negative outcomes, with progression from PCRR to cirrhosis or chronic ductopenic rejection (CDR). Patients who had hepatitis C virus were more likely to develop cirrhosis rather than CDR following the PCRR diagnosis (P = .01). Twenty-three (65.7%) patients had at least one prior episode of T-cell-mediated rejection before being diagnosed with PCRR. DSAs were positive in 16 of 19 patients assessed, and C4d immunostaining was positive in 9 of 10 patients. CONCLUSIONS: Development of PCRR negatively affects liver allograft outcomes and patient survival after LT. The presence of DSA and C4d in PCRR patients supports it to be within the histologic spectrum of AMR.

Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

Acute kidney injury (AKI) is common in hospitalized patients with cirrhosis. Hepatorenal syndrome (HRS) is a type of AKI known as HRS-AKI. It is a severe complication of cirrhosis with high morbidity and mortality. While certain vasoconstrictor medications have been shown to improve HRS-AKI, no clear transplant-free survival benefit has been reported with medical therapies. Patients with HRS-AKI should be considered for urgent liver transplantation evaluation. In this review, we discuss the most recent updates on the definition, diagnosis, and management of AKI in cirrhosis, with special a emphasis on HRS.

Liver transplantation in developing countries.

With the increasing incidence and prevalence of end-stage liver disease, demand for donor grafts continues to increase. Approaches on maximizing the potential donor grafts vary depending on the region. This review aims to summarize the current practice of liver transplantation with an emphasis on challenges encountered in developing countries.

Cell-free methylation of RASSF1 and CDKN2AIP genes in the diagnosis of hepatocellular carcinoma associated with hepatitis B virus cirrhosis.

Background and Aim: Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) methylation of tumor suppressor genes are emerging potential biomarkers in HCC. We aimed to evaluate the cfDNA methylation status of RASSF1 and CDKN2AIP genes in patients with liver cirrhosis (LC) with or without HCC caused by HBV. Materials and Methods: A total of 47 patients with HBV cirrhosis were included in the study. Patients were divided into two groups: HCC and LC (HCC+LC, n=22) and HBV cirrhosis only (LC, n=25). cfDNA was isolated from the plasma samples of the patients. Methylation analysis was performed for RASSF1 and CDKN2AIP genes. Results: Mean methylation percentage of CDKN2AIP gene was 0.001±0.004% in the HCC+LC group and 0.008±0.004 % in the LC only group. The mean methylation percentage of RASSF1 gene was 5.1±16.1% in the HCC+LC group and 9.7±25.9% in the LC only group. The methylation rate of CDKN2AIP was significantly lower in the HCC+LC group (p=0.027). A positive correlation was found with the absence of cfDNA methylation of CDKN2AIP gene in the presence of HCC (R=0.667, p=0.018). Conclusion: cfDNA methylation of CDKN2AIP and RASSF1 genes may provide important diagnostic information regarding the development of HCC in the setting of HBV cirrhosis.

Identification and clinical significance of nodular regenerative hyperplasia in primary sclerosing cholangitis.

Background and Aim: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intrahepatic and extrahepatic bile ducts. PSC is frequently associated with inflammatory bowel disease (IBD). Nodular regenerative hyperplasia (NRH) can occur in IBD with the use or even in the absence of thiopurine treatment. We aimed to study the significance of the presence of NRH and obliterative portal venopathy (OPV), both causes of non-cirrhotic portal hypertension (NCPH), in patients having PSC. Methods: Patients with PSC and concurrent NRH on liver biopsy were identified from the digital pathology database covering the period 2003-2019. Evaluation of liver biopsy and the original diagnoses were confirmed on review based on standard histological features diagnostic for NRH and OPV. Clinical and laboratory data were obtained from electronic medical records. Results: Thirty-one patients (21 male, 10 female; median age at biopsy 40.1 years) were included in the study. Twelve (38.7%) patients had OPV in addition to NRH on the liver biopsy. Nineteen (61.2%) patients had IBD including 11 with Crohn's disease (CD), 7 with ulcerative colitis (UC), and 1 with indeterminate colitis. Thirteen (41.9%) patients had evidence of portal hypertension, 10 (32.2%) with esophageal varices, 4 (12.9%) with history of variceal bleeding, 6 (19.3%) with ascites, and 14 (12.9%) with splenomegaly. Eleven (35.4%) patients had a cirrhotic-appearing liver on imaging. Twelve (38.7%) patients had a history of prior or current thiopurine use. Conclusions: The current study suggests that NRH with or without OPV independently occurs in patients having PSC and may lead to NCPH, even in the absence of concurrent IBD and/or thiopurine therapy.