Search Results (71)

Background. The existing literature highlights a lack of comparative studies between subtypes of cholangiocarcinoma (CC) and the impact of misclassification on the epidemiological parameters. Methods. A retrospective study was conducted to evaluate the surgical outcomes. The authors used Poisson regression with modified errors to calculate the risk ratios (RR) and reported post-estimation marginal effects. Coefficient estimates, variance inflation factors, and Pearson’s goodness-of-fit test statistics were used to check for multicollinearity and model fit, respectively. We also performed a reclassification analysis by modeling Klatskin tumors (PCC) as extrahepatic (ECC), reclassifying them as intrahepatic (ICC), and comparing the corresponding changes in estimates. Results. Regression analysis revealed an increased risk of death in patients with ICC (RR = 2.05, 95% CI 1.11–3.78) and PCC (RR = 2.03, 95% CI 0.97–4.24) compared to those with DCC. When PCC was analyzed as an ECC, the ICC revealed an RR of 1.52 (95% CI 0.84–2.73). Further reclassification of PCC showed an RR of 2.04 for ICC (95% CI: 1.53–3.53). The adjusted marginal effects saw a reduction in the death probability for both ICC and ECC. However, post hoc analyses revealed insufficient evidence for differences between the reclassified models. Conclusions. Patients with DCC had slightly better prognosis compared to ICC and PCC. We found no differences in survival between ICC and ECC (combining DCC and PCC). The decrease in mortality risk due to reclassification in both groups was not confirmed statistically. Future studies should focus on statistical evidence when referring to the Will Rogers phenomenon, instead of inferring from raw comparisons. Full article

Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome characterized by an acute decompensation of chronic liver disease in association with extrahepatic organ failure(s) and a high short-term mortality. Despite its increasing clinical relevance, there is no internationally standardized definition of ACLF to date. This review provides a comprehensive overview of current ACLF definitions, underlying pathogenic mechanisms, frequent precipitating events, and current treatment strategies. While liver transplantation remains the only curative treatment option, its role in the setting of ACLF is controversially debated, and patient selection remains complex due to high perioperative risk. Thus, the review article describes the current role of liver transplantation in patients with ACLF and describes novel prognostic scoring systems (e.g., TAM core, SALT-M model) that may be helpful in selecting suitable transplant candidates. Further emerging treatment options for ACLF include extracorporeal liver support systems, therapeutic plasma exchange, and immune-modulating approaches targeting toll-like receptor signaling that offer promising adjunctive strategies, though clinical evidence remains limited. Given the high burden and complexity of ACLF, harmonized definitions and evidence-based therapeutic frameworks are urgently needed to improve patient care and optimize transplant prioritization. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelial lining of the intrahepatic or extrahepatic bile ducts. Although rare globally, its mortality closely mirrors incidence due to late-stage presentation of the disease and limited curative options. While surgical resection and liver transplantation remain the cornerstone treatments for those with resectable disease, endoscopic techniques have emerged as versatile tools for diagnosis, therapy, and palliation. In recent years, there have been major advancements in endoscopic therapies, including radiofrequency ablation (RFA), intraluminal brachytherapy (ILBT), and photodynamic therapy (PDT). The current narrative review serves to provide an overview of current and emerging endoscopic strategies for CCA, emphasizing diagnostic capabilities, therapeutic approaches, palliative interventions, and future directions. Full article

Background: Cholangiocarcinoma, malignancies arising from the intrahepatic and extrahepatic bile ducts, has increased in incidence in the United States over the past few decades. The reported incidence of cholangiocarcinomas is high, particularly in specific racial groups such as Asian and Pacific Islander patients. Race also significantly impacts disparities in healthcare utilization and clinical outcomes. Our study focused on the impact of race on admission, clinical outcomes, and disposition of cholangiocarcinoma. Methods: We performed a retrospective analysis of cholangiocarcinoma-related hospital admissions, using the National Inpatient Sample for the year 2022. Patients were stratified according to race into the following groups: White, African American, Hispanic, Asian or Pacific Islander, Native American, and Other. The data analysis was performed using STATA/BE version 18.5. Univariable and multivariable logistic regression models were applied to evaluate the relationship between race and clinical and healthcare utilization outcomes. Results: In 2022, 7479 hospitalizations were recorded for cholangiocarcinoma in the United States. Among these, 65.99% were White, 13.27% Hispanic, and 10.13% African American. There was a statistically significant difference in gender distribution across racial groups (p < 0.001), with males comprising the majority in all groups. Males outnumbered females in all racial groups except among the Hispanic group. Significant racial disparities in mortality were observed, with White patients showing a mortality rate of 6.69%, compared to higher rates among African American (9.76%), Native American (8.51%), and Asian or Pacific Islander (8.09%) patients, while Hispanic (5.04%) and Other (5.88%) groups had lower rates (p < 0.001). Conclusions: The study underscores the racial disparities among cholangiocarcinoma hospitalizations, with African American, Native American, and Asian patients facing disproportionately higher mortality and poorer in-hospital outcomes compared to White patients. This analysis highlights the healthcare strategies and policy reforms to promote equitable treatment by mitigating these disparities and to improve cholangiocarcinoma outcomes. Full article

Metabolic dysfunction-associated steatotic fatty liver disease (MASLD) is a worsening global health issue, affecting over one-third of the adult population and representing the leading cause of liver-related morbidity and mortality. MASLD is not only a key precursor to chronic liver disease, but also a systemic condition that leads to numerous extrahepatic complications, increasing the risk of cardiovascular diseases, chronic kidney disease, type 2 diabetes, and certain cancers. The primary reference method for assessing liver fibrosis, allowing for precise determination of its location and severity, remains liver biopsy. However, it is an invasive procedure and involves certain risks. In recent years, the importance of MASLD diagnosis using noninvasive diagnostic methods has been increasing, including serological markers, methods based on multi-omics, and imaging techniques such as liver elastography. This review presents data on the diagnosis and evaluation of this disease that may find application in future clinical practice. The focus is on presenting both currently used and newly identified noninvasive diagnostic methods that open up the prospect of gradually replacing biopsy in the diagnosis of MASLD. Full article

Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic-associated fatty liver disease (MAFLD). This review aims to synthesize current evidence on the pathophysiology and clinical implications of nephrological, pulmonary, and dermatological manifestations among NAFLD/MAFLD patients. In order to find safe and efficient treatments, NAFLD/MAFLD has emerged as a primary concern for hepatologists worldwide. Methods: We conducted a comprehensive review of the literature from major databases, focusing on studies that evaluated the extrahepatic manifestations of NAFLD/MAFLD. Emphasis was placed on identifying pathophysiological mechanisms and assessing their clinical impact on renal, pulmonary, and dermatological systems. Results: Recent developments in the management of chronic viral hepatitis have lowered the mortality rate associated with chronic liver disease. However, the prevalence of NAFLD/MAFLD continues to rise, making chronic liver disease a significant health concern for the future. An increasing percentage of patients on liver transplant waiting lists now have cirrhosis and hepatocellular carcinoma due to non-alcoholic liver disease. Furthermore, the incidence and prevalence of chronic kidney disease have surged, linking NAFLD/MAFLD to higher morbidity, mortality, and healthcare costs. Conclusions: NAFLD/MAFLD is underdiagnosed and underappreciated, yet its incidence is rapidly increasing, raising concerns about a potential global epidemic. Given its multisystemic impact—extending to renal, pulmonary, and dermatological complications—it is crucial to develop interdisciplinary strategies for early detection and effective management of the disease. Full article

Chronic liver disease (CLD) in children poses significant challenges, necessitating timely management to mitigate morbidity and mortality. Liver transplantation (LT) has emerged as a transformative intervention, offering improved long-term survival for paediatric patients with CLD. This review explores the evolving landscape of liver transplantation, focusing on indications and timing considerations. The aetiology of CLD is diverse, encompassing intrahepatic, extrahepatic cholestatic conditions, metabolic diseases, malignancy, and drug-induced liver injury. LT is indicated when children exhibit signs of hepatic decompensation, necessitating a comprehensive evaluation to assess transplant suitability. Indications for LT include biliary atresia, inborn errors of metabolism, hepatocellular carcinoma, and emerging indications such as mitochondrial hepatopathies and acute on chronic liver failure. The timing of transplantation is critical, emphasizing the need for early recognition of decompensation signs to optimise outcomes. Advancements in LT techniques and immunosuppressive therapies have enhanced patient and graft survival rates. Various transplant modalities, including reduced-size LT and living-related LT, offer tailored solutions to address the unique needs of paediatric patients. While LT represents a cornerstone in the management of paediatric CLD, careful patient selection, multidisciplinary collaboration, and ongoing refinements in transplant protocols are imperative for optimizing outcomes and addressing the evolving landscape of paediatric liver disease management. Full article

Non-alcoholic fatty liver disease (NAFLD) has frequently been associated with obesity, type 2 diabetes (T2D), and dyslipidemia, all of which are shared by increased insulin resistance. It has become the most common liver disorder in Korea as well as in developed countries and is therefore associated with an increased health burden of morbidity and mortality. It has an association with T2D, and T2D increases the risk of cirrhosis and related complications. NAFLD encompasses a disease continuum from simple steatosis to non-alcoholic steatohepatitis which is characterized by faster fibrosis progression. Although its liver-related complication is estimated to be, at most, 10%, it will be a leading cause of cirrhosis and hepatocellular carcinoma soon in Korea. Although the main causes of death in people with NAFLD are cardiovascular disease and extra-hepatic malignancy, advanced liver fibrosis is a key prognostic marker for liver-related outcomes and can be assessed with combinations of non-invasive tests in the community. A number of components of metabolic syndrome involved could be another important prognostic information of NAFLD assessed easily in the routine care of the community. There is a few approved therapies for NAFLD, although several drugs, including antioxidants, attract practitioners’ attention. Because of the modest effect of the present therapeutics, let alone complex pathophysiology and substantial heterogeneity of disease phenotypes, combination treatment is a viable option for many patients with NAFLD in the Korean community. Comprehensive approach taking healthy lifestyle and weight reduction into account remain a mainstay to the prevention and treatment of NAFLD. Full article

Background: Liver function and the presence of portal hypertension, as well as the urgency and type of surgery, are prognostic factors in advanced chronic liver disease (ACLD) patients undergoing extrahepatic major surgeries. Emergent surgery in ACLD patients has 4–10 times higher mortality rates than elective surgery. However, perioperative management improvements have been made in recent years. Methods: This is a retrospective, observational, and unicentric study of 482 patients with ACLD who underwent major surgery from 2010 to 2019. We compared baseline characteristics and postoperative mortality according to the presence of ascites, the emergency, and the surgery period. Results: In total, 140 (29%) patients had ascites, and 191 (39.6%) underwent urgent surgeries. The 90-day mortality was 2.8-fold higher in patients with ascites [HR (95%CI) 2.8 (1.6–5.0); p = 0.001] and 3-fold higher in urgent surgeries [3.0 (1.6 − 5.5); p < 0.001)]. Urgent surgeries in patients with ascites revealed the highest mortality risk [6.3 (2.7–14.8); p < 0.001)], which persisted in current (2015–2019) surgeries [12.8 (2.9–56.5); p = 0.001)]. Portal hypertension was meaningful in patients undergoing abdominal surgery. Conclusions: ascites and emergent surgery increase the mortality risk of patients with ACLD despite the recent perioperative improvements. Full article

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several studies have investigated the impact of HEV on the male reproductive system; however, the available data are limited and conflicting. Assessment of the patients’ ejaculates/semen samples revealed that HEV particles are excreted in these fluids in cases of chronic infection but not acute infection. The excreted HEV particles are infectious to in vivo animal models and in vitro cell culture. However, the effect of HEV infection on male infertility is not confirmed. One study including human samples showed male infertility associated with HEV genotype 4 infection. Studies of HEV infection in animal models such as pigs, gerbils, and mice showed that HEV infection caused distortion on the testes, damage of the blood–testis barrier, and induction of inflammatory responses leading to abnormalities in the sperm. The excretion of HEV in the semen fluids raises concerns about HEV transmission via sexual transmission. However, all available data do not confirm the transmission of HEV through sexual intercourse. This review aims to summarize and critically assess the available studies investigating the influence of different HEV genotypes on the male reproductive system, providing insights into whether HEV contributes to reproductive impairment in men. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily developing in the context of chronic liver disease. Traditional prevention has focused on liver-specific interventions like antiviral therapies and surveillance. However, extrahepatic factors also significantly contribute to HCC risk. This review explores comprehensive strategies for HCC prevention, including both hepatic and extrahepatic factors. Methods: An extensive literature search of peer-reviewed articles up to October 2024 was conducted, focusing on studies addressing HCC prevention strategies. Studies that focused on both hepatic and extrahepatic factors were included. Data were extracted and synthesized to provide an overview of current prevention strategies and their effectiveness in reducing HCC incidence. Results: Hepatitis B vaccination and antiviral treatments for hepatitis B and C significantly reduce HCC incidence. Lifestyle modifications—such as reducing alcohol consumption, maintaining a healthy weight through diet and exercise, and smoking cessation—are crucial in lowering HCC risk. Environmental measures to limit exposure to aflatoxins and other hazards also contribute to prevention. Regular surveillance of high-risk groups enables early detection and improves survival rates. Emerging strategies like immunotherapy and gene therapy show potential for further reducing HCC risk. Conclusions: A comprehensive approach combining medical interventions, lifestyle changes, and environmental controls is essential for effectively decreasing HCC incidence globally. Implementing these combined measures could significantly reduce the global burden of HCC. Full article

Hepatitis C virus (HCV) has emerged as a major global health concern and, if left untreated, can lead to significant liver damage, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC). Approximately 40% of patients with HCV infection experience extrahepatic manifestations, including renal involvement. HCV-related renal disease is of significant importance among patients with chronic kidney disease (CKD), leading to higher morbidity and mortality. The renal damage due to HCV infection primarily results from cryoglobulinemia and glomerulonephritis, with conditions such as membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) being most prevalent. Despite advancements in treatment, including the use of directly acting antiviral agents (DAAs), renal complications remain a significant burden in untreated patients. HCV-positive patients on hemodialysis (HD) or those who have undergone kidney transplantation face increased mortality rates compared to their HCV-negative counterparts. Managing HCV infection before kidney transplantation is crucial to mitigate the risk of HCV-related renal complications. Conversely, kidney transplantation from HCV-infected donors is well established, as post-transplant treatment for HCV is safe and effective, potentially reducing mortality and morbidity for patients on transplant waiting lists. This review aims to provide a comprehensive analysis of the renal manifestations of HCV, emphasizing the importance of early diagnosis and treatment to improve patient outcomes. Full article

Background: Primary sclerosing cholangitis (PSC) is an immune-mediated disease that has an unfavorable prognosis and needs a liver transplant (LT). The aim of this paper was to show the usefulness of the Majoie classification on magnetic resonance cholangiopancreatography (MRCP) images in assessing the prognosis in adult patients with PSC. Methods: Our work presents a retrospective monocentric study performed on 64 adult patients with PSC of the large bile ducts. Two radiologists evaluated the MRCP of diagnosis and calculated MRCP scores using the Majoie classification. Liver-related outcome (LT or liver-related death) was marked as a primary endpoint. Results: Univariate analysis showed that patients with more severe lesions (sum score of intrahepatic and extrahepatic ducts > 3) had a lower age at diagnosis, of 37.2 years, complicated with liver cirrhosis (53.1% of patients) and recurrent cholangitis (28.1%) p < 0.05, without significant differences in mortality, association with IBD or LT. Concordance analysis between MRCP prognostic scores and progression to a PSC-related event showed a moderate relationship (c-statistic 0.662), and a good AUROC was observed for the UKPSC score (0.893) and the MRS (0.936). Conclusions: In the study, we observed a good correlation between the imaging scores based on the Majoie classification and the evolution of the patients. These scores were outperformed by the UKPSC, MRS, and PREsTo clinical models. Their utility was best in predicting recurrent cholangitis. Full article

The burden of chronic liver disease is globally increasing at an alarming rate. Chronic liver injury leads to liver inflammation and fibrosis (LF) as critical determinants of long-term outcomes such as cirrhosis, liver cancer, and mortality. LF is a wound-healing process characterized by excessive deposition of extracellular matrix (ECM) proteins due to the activation of hepatic stellate cells (HSCs). In the healthy liver, quiescent HSCs metabolize and store retinoids. Upon fibrogenic activation, quiescent HSCs transdifferentiate into myofibroblasts; lose their vitamin A; upregulate α-smooth muscle actin; and produce proinflammatory soluble mediators, collagens, and inhibitors of ECM degradation. Activated HSCs are the main effector cells during hepatic fibrogenesis. In addition, the accumulation and activation of profibrogenic macrophages in response to hepatocyte death play a critical role in the initiation of HSC activation and survival. The main source of myofibroblasts is resident HSCs. Activated HSCs migrate to the site of active fibrogenesis to initiate the formation of a fibrous scar. Single-cell technologies revealed that quiescent HSCs are highly homogenous, while activated HSCs/myofibroblasts are much more heterogeneous. The complex process of inflammation results from the response of various hepatic cells to hepatocellular death and inflammatory signals related to intrahepatic injury pathways or extrahepatic mediators. Inflammatory processes modulate fibrogenesis by activating HSCs and, in turn, drive immune mechanisms via cytokines and chemokines. Increasing evidence also suggests that cellular stress responses contribute to fibrogenesis. Recent data demonstrated that LF can revert even at advanced stages of cirrhosis if the underlying cause is eliminated, which inhibits the inflammatory and profibrogenic cells. However, despite numerous clinical studies on plausible drug candidates, an approved antifibrotic therapy still remains elusive. This state-of-the-art review presents cellular and molecular mechanisms involved in hepatic fibrogenesis and its resolution, as well as comprehensively discusses the drivers linking liver injury to chronic liver inflammation and LF. Full article

Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95–98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8–11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96–2.48) for IFN-based therapy, 4.27% (95% CI 2.93–6.2) for DAA and 0.89% (95% CI 0.4–1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment. Full article