Journal of Clinical and Experimental Hepatology最新文献

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.

Introduction

Circulating tumor cells are a promising biomarker in many malignancies. CTC dissemination during the operative procedure can lead to disease recurrence. The effect of preoperative transarterial embolization on the release of CTCs and miRNA panels and oncological outcomes in large hepatocellular carcinomas has been evaluated.

Materials and methods

The study included non-metastatic HCC >5 cm in size, that were completely resected after TAE (n = 10). Blood was collected pre-TAE, post-TAE, postoperative (day 2,30 and 180) and analyzed for the presence of CTC and miRNA (miR-885-5p, miR-22-3p, miR-642b-5p). The samples were subjected to CTC enrichment, isolation and staining using the markers CD45, EpCAM, and cytokeratin (CK). The data was analyzed using Gene Expression Suite software.

Results

The CTC enumeration resulted in three groups: Group 1- CTC present at both pre-TAE and postoperative day 30 (n = 4), Group 2- CTC present at pre-TAE and clearing at postoperative day 30 (n = 2), Group 3- No CTC detected at any stages (n = 3). Group 2 patients had better survival compared with the other groups. Downregulation of miRNA 22-3p also had favorable prognostic implications.

Conclusion

Although preoperative TAE does not seem to impact CTC shedding, CTC clearance may prove to be a valuable biomarker in prognosticating HCC. A larger study to evaluate the significance of CTCs as a prognostic marker is warranted to further evaluate these findings.

Background

There is no accepted way to define difficult donor hepatectomy (DiffDH) during open right live donor hepatectomy (ORLDH). There are also no studies exploring association between DiffDH and early donor outcomes or reliable pre-operative predictors of DiffDH.

Methods

Consecutive ORLDH performed over 18 months at a single center were included. Intraoperative parameters were used to develop an objective definition of DiffDH. The impact of DiffDH on early postoperative outcomes and achievement of textbook outcome (TO) was evaluated. Donor morphometry data on axial and coronal sections of donor computed tomography (CT) at the level of portal bifurcation were collected. Donor and graft factors predictive of DiffDH were evaluated using univariate and multivariate logistic regression.

Results

One-hundred-eleven donors (male: 40.5%, age: 34 ± 9.5 years) underwent ORLDH during the study period. The difficulty score was constructed using five intraoperative parameters, i.e., operating time, transection time, estimated blood loss, need for intraoperative vasopressors, and need for Pringle maneuver. Donors were classified as DiffDH (score ≥ 2) or standard donor hepatectomy (StDH) (score <2). Twenty-nine donors (26%) were classified as DiffDH. DiffDH donors suffered greater all-cause morbidity (P = 0.004) but not major morbidity (Clavien–Dindo score >2; P = 0.651), more perioperative transfusion (P = 0.013), increased postoperative systemic inflammatory response syndrome (P = 0.034), delay in achieving full oral diet (P = 0.047), and a 70% reduced chance of achieving TO as compared to StDH (P = 0.007). On logistic regression analysis, increasing right lobe anteroposterior depth (RLdepth) was identified as an independent predictor of DiffDH (Odds ratio: 2.0 (95% confidence interval = 1.2, 3.3), P < 0.006). Receiver operating characteristic curve analysis identified an RLdepth of >14 cm as the best predictor of DiffDH (sensitivity:79%, specificity: 66%, area under curve = 0.803, P < 0.001).

Conclusion

We report a novel definition of DiffDH and show that it is associated with worse postoperative outcomes, including a lesser chance of achieving TO. We also report that DiffDH can be predicted from readily available donor CT parameters.

Acute hepatic failure may occasionally be complicated by toxic liver syndrome. Emergency hepatectomy for stabilization followed by delayed graft implantation is a recognized strategy in such cases in the setting of deceased donor liver transplantation. Living donor liver transplantation adds additional complexity to this scenario as the donor liver is a directed donation and failure to stabilize the patient after emergency hepatectomy can lead to a futile live donor hepatectomy, hepar-divisum, or an orphan graft. We report a case where the two-stage strategy was utilized to circumvent this situation. A patient with toxic liver syndrome underwent emergency hepatectomy and was closely monitored in the operating theater. A live donor hepatectomy was started after the recipient demonstrated cardiovascular and neurological stabilization. Graft implantation was completed after an anhepatic period of 9.45 h. To our knowledge, this is the first reported instance of using the two-stage strategy in living-donor-liver-transplantation for toxic liver syndrome to prevent futile donor surgery and achieve double equipoise.