Journal of Clinical and Experimental Hepatology最新文献

Background

Hepatocellular carcinoma (HCC) is the third prime cause of malignancy-related mortality worldwide. Early and accurate identification of HCC is crucial for good prognosis, efficacy of therapy, and survival rates of the patients. We aimed to develop a machine-learning model incorporating differentially expressed RNA signatures with laboratory parameters to construct an RNA signature-based diagnostic model for HCC.

Methods

We have used five classifiers (KNN, RF, SVM, LGBM, and DNNs) to predict the liver disease (HCC). The classifiers were trained on 187 samples and then tested on 80 samples. The model included 22 features (age, sex, smoking, cirrhosis, non-cirrhosis, albumin, ALT, AST bilirubin (total and direct), INR, AFP, HBV Ag, HCV Abs, RQmiR-1298, RQmiR-1262, RQmiR-106b-3p, RQmRNARAB11A, and RQSTAT1, RQmRNAATG12, RQLnc-WRAP53, RQLncRNA- RP11-513I15.6).

Results

LGBM achieved the highest accuracy of 98.75% in predicting HCC among all models surpassing Random Forest (96.25%), DNN (91.25%), SVC (88.75%), and KNN (87.50%).

Conclusion

Our machine-learning model incorporating the expression data of RAB11A/STAT1/ATG12/miR-1262/miR-1298/miR-106b-3p/lncRNA-RP11-513I15.6/lncRNA-WRAP53 signature and clinical data represents a potential novel diagnostic model for HCC.

Liver regeneration (LR) is a unique biological process with the ability to restore up to 70% of the organ. This allows for the preservation of liver resections for various liver tumors and for living donor liver transplantation (LDLT). However, in some cases, LR is insufficient and interventions that can improve LR are urgently needed. Gut microbiota (GM) is one of the factors influencing LR, as the liver and intestine are intimately connected through the gut–liver axis. Thus, healthy GM facilitates normal LR, whereas dysbiosis leads to impaired LR due to imbalance of bile acids, inflammatory cytokines, microbial metabolites, signaling pathways, etc. Therefore, GM can be considered as a new possible therapeutic target to improve LR. In this review, we critically observe the current knowledge about the influence of gut microbiota (GM) on liver regeneration (LR) and the possibility to improve this process, which may reduce complication and mortality rates after liver surgery. Although much research has been done on this topic, more clinical trials and systemic reviews are urgently needed to move this type of intervention from the experimental phase to the clinical field.

Objective

Hepatic encephalopathy (HE) is a marker of poor prognosis in adults with chronic liver disease (CLD). We prospectively studied the prevalence and precipitants of HE in children with CLD as there is a paucity of literature on the same.

Methods

Children (1–18 years) admitted with CLD were examined daily for the presence and grading of HE (West Haven/Whittington grading). Precipitants were classified as infection, dyselectrolytemia, gastrointestinal bleeding, constipation and dehydration. Changes in grades of HE and outcome were noted.

Results

One hundred and sixty children (age 120 [84–168] months) were enrolled. HE was present in 50 (31.2%) patients with a total of 61 episodes. Maximum grade of HE was grade I (n = 16), II (n = 23), III (n = 11) and IV (n = 11). Forty-two cases had single and 8 had recurrent (2–5) episodes. Median duration of HE episodes was 96 (72–192) hours. Precipitants were identified in 55/61 (90.2%) episodes with infection (45/61, 73.7%) and dyselectrolytemia (33/61, 54%) being the most common. Lower albumin and sodium, higher INR and presence of infection were significantly associated with presence of HE. Overall, HE resolved in 33 (54%) episodes, while it progressed and persisted in 28 (45.9%) episodes. Patients with HE had a poorer outcome (25/50 vs 13/110; P < 0.01) with both higher in-hospital (11/50 vs 9/110; P = 0.02) and 1-month post discharge (14/39 vs 4/101; P < 0.01) mortality than those without HE.

Conclusion

One-third of admitted CLD children have HE, with identifiable precipitants in 90% of cases. Children with HE have poorer liver functions, higher rate of infections and worse outcome than those without HE.

Background

Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia.

Methods

Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/β-catenin (W/B) signaling-related molecules (β-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC).

Results

Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both P < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, P = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, P = 0.005). No significant differences were found in the proportions of B/S, W/B, and −/− subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and −/− subgroups (90%), whereas Japanese VETC cases (10%, P = 0.030) were nonviral (100%) and W/B subgroups (75%).

Conclusion

IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.

Liver transplantation offers a new lease of life to patients with end-stage liver disease and hepatocellular carcinoma. However, the implantation of an exogenous allograft and the accompanying immunosuppression bring their own challenges. Moreover, the persistence of risk factors for the initial liver insult place the new graft at a higher risk of damage. With the increasing number of liver transplants along with the improvement in survival posttransplant, the recurrence of primary disease in liver grafts has become more common. Pre-2015, the most common disease to recur after transplant was hepatitis C. However, directly acting antivirals have nearly eliminated this problem. The greatest challenge of disease recurrence we now face are those of nonalcoholic steatohepatitis, alcohol-related liver disease, and primary sclerosing cholangitis. We focus on the epidemiology and pathophysiology of the recurrence of primary disease after transplant. We also discuss means of early identification, risk stratification, prevention, and management of recurrent primary disease after liver transplantation.

Hepatocellular carcinoma (HCC) is one of the few cancers with a 5-year survival that has remained below 20%; however, prognosis differs by tumor stage at diagnosis. Curative treatment options among patients with early-stage HCC afford a median survival of 5–10 years. Accordingly, international society guidelines recommend semi-annual HCC surveillance in at-risk patients, including those with cirrhosis or high-risk chronic hepatitis B infection. Surveillance is associated with increased early-stage HCC detection and curative treatments, leading to reduced HCC-related mortality. Abdominal ultrasound has been the cornerstone for HCC surveillance for the past two decades, but recent data have highlighted its suboptimal sensitivity for early-stage HCC detection, particularly in patients with obesity and those with non-viral etiologies of liver disease. The combination of ultrasound plus alpha fetoprotein (AFP) has higher sensitivity for early-stage HCC detection than ultrasound alone, although the combination still misses over one-third of HCC at an early stage. Emerging imaging and blood-based biomarker strategies have promising data in biomarker phase 2 (case–control) and phase 3 (cohort) studies. Beyond ultrasound, Magnetic resonance imaging (MRI) is the best-studied imaging strategy, with superior sensitivity and specificity compared to ultrasound in a cohort study. Abbreviated MRI protocols have been proposed to address concerns about MRI radiological capacity, costs, and patient acceptance. Of biomarker strategies, GALAD (a panel including gender, age, AFP, AFP-L3, and DCP) is the best validated, with promising sensitivity for early-stage HCC detection in a national multi-center cohort study. Liquid biopsy biomarkers, including methylated DNA markers, have also shown promising accuracy in case–control studies. Abbreviated MRI and GALAD are now entering prospective trials that examine clinical outcomes such as early-stage HCC detection and screening-related harms, which are essential data to understand for adoption in clinical practice. As additional surveillance strategies become available, it will allow an era of precision surveillance in which optimal surveillance modalities are tailored to individual patient risk and expected test performance.

Acute liver failure (ALF) typically presents with encephalopathy and impairment in the synthetic function of the liver. Weight loss supplements have been associated with ALF, and their use has only been increasing in the United States. We report a case of a 42-year-old woman with a history of Gilbert's syndrome who presented to the hospital with ALF secondary to weight loss supplements, who ultimately required liver transplantation. This is the first known case of conjugated linoleic acid (CLA) toxicity requiring liver transplantation in the United States.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a significant cause of morbidity and mortality, especially in patients with chronic liver disease. As a reflection of geographical variations in India, there is significant variation in the prevalence and etiological factors of HCC. In contrast to previous studies reporting viral hepatitis as the most common etiology, recent data indicates a changing etiological pattern of cirrhosis and HCC, with alcohol and metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as the foremost cause. Thus, there was a need for an updated review of the current literature and databases for the changing epidemiology and etiological spectrum of HCC in India. The review included data primarily from the National Cancer Registry Program and the Global Burden of Diseases, Injuries, and Risk Factors Study, with the inclusion of other studies from India. The highlights of the present review are summarized in the following lines. Although the current incidence (2.15 per 100,000), prevalence (2.27 per 100,000), and mortality (2.21 per 100,000) rate of HCC in India remain lower compared to the global data, the annual rates of change in these parameters are higher in India. Among Indians, the present incidence, prevalence, and mortality related to HCC are higher in males, while the annual rate of change is higher in females. The Northeastern states have higher incidence, prevalence, and mortality related to HCC, but the Western states of Gujarat, Maharashtra, Goa, and Kerala are emerging as newer hotspots with higher annual rates of change in incidence, prevalence, and mortality. The incidence of HCC related to hepatitis B is on a downtrend, while those related to alcohol and MASLD are rising. Public health initiatives, awareness campaigns, and focused treatments are all necessary to combat these changes, particularly in areas with high incidence rates.