Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.

BACKGROUND AND AIMS: Non-A-E hepatitis (NAEH) not leading to acute liver failure (ALF) is poorly documented. The objective was to compare clinical and laboratory features of uncomplicated acute NAEH with acute viral (AVH) and autoimmune hepatitis (AIH) and histopathology in NAEH and AIH. METHODS: Cases of hepatocellular jaundice were included. These were grouped into AVH, AIH and NAEH based on clinical, laboratory and, when indicated, liver biopsy findings. NAEH and AIH were followed up at three months. RESULTS: Of 336 patients with hepatocellular jaundice, 15 (5%) were NAEH, 25 (7%) acute AIH and 45 (14%) AVH. Among NAEH patients, seven (46.7%) were males with a mean age of presentation 39 years. Jaundice (100%) was the most common presentation of NAEH. Peak bilirubin was 10.7 mg/dL. Peak aspartate and alanine aminotransferase (AST, ALT) were 512 and 670 U/L. Five (33.3%) patients had positive anti-nuclear antibody and one had anti-smooth muscle antibody. Mean immunoglobulin G (IgG) levels were 1829. On liver biopsy, all had ballooning degeneration, four (26.7%) had mild and three (20%) moderate interface hepatitis, four (26.7%) mild lymphoplasmacytic infiltrate, one (6.7%) rosette formation, bridging necrosis in none and stage 1 fibrosis in one. Comparing NAEH with AIH, AIH showed significantly older age at presentation, female predisposition, past history of jaundice, lower ALT, more autoantibodies, higher IgG, higher grade interface hepatitis, lymphoplasmacytic infiltrate, rosette formation and higher bilirubin, AST at three months. NAEH and viral hepatitis had similar features. CONCLUSION: Etiology of NAEH is unlikely to be autoimmune and is probably viral, unidentified as yet. Uncomplicated NAEH likely has self-limiting course even without specific treatment.

Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma. / è‚ç‚Žç— æ¯’æ„ŸæŸ“å¯¼è‡´è‚ç»†èƒžç™Œå‘ç”Ÿçš„å ç–«æœºåˆ¶ç ”ç©¶è¿›å±•.

Hepatocellular carcinoma (HCC) is a serious neoplastic disease with increasing incidence and mortality, accounting for 90% of all liver cancers. Hepatitis viruses are the major causative agents in the development of HCC. Hepatitis A virus (HAV) primarily causes acute infections, which is associated with HCC to a certain extent, as shown by clinicopathological studies. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections lead to persistent liver inflammation and cirrhosis, disrupt multiple pathways associated with cellular apoptosis and proliferation, and are the most common viral precursors of HCC. Mutations in the HBV X protein (HBx) gene are closely associated with the incidence of HCC, while the expression of HCV core proteins contributes to hepatocellular lipid accumulation, thereby promoting tumorigenesis. In the clinical setting, hepatitis D virus (HDV) frequently co-infects with HBV, increasing the risk of chronic hepatitis. Hepatitis E virus (HEV) usually causes acute infections. However, chronic infections of HEV have been increasing recently, particularly in immuno-compromised patients and organ transplant recipients, which may increase the risk of progression to cirrhosis and the occurrence of HCC. Early detection, effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer, while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies. This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.

Sleep patterns, genetic predisposition, and risk of chronic liver disease: A prospective study of 408,560 UK Biobank participants.

BACKGROUND: Little is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk. METHODS: We included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7-8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk. RESULTS: During a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0-1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %). LIMITATIONS: Measurement error was unavoidable for self-reported data on sleep behaviors. CONCLUSIONS: Our analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern.

Viral Hepatitis Necessitating Liver Transplantation in Children.

Viral hepatitis accounts for a significant global disease burden and mortality, both in children and adults. There are significant differences in the viral etiology, epidemiology, and complications in children worldwide. Children of all ages may have devastating complications with a significant risk of mortality and long-term morbidity because of viral hepatitis. Liver transplantation is the only curative option for pediatric patients with end-stage liver disease, hepatocellular carcinoma, or acute liver failure because of viral hepatitis. The introduction of universal vaccination for hepatitis B across the world and hepatitis A in some countries had led to significant changes in the incidence of disease and the need for liver transplantation for the complications of viral hepatitis in children. The development of effective treatment with directly acting antiviral agents for hepatitis C has already transformed outcomes in adults and children and reduced the need for liver transplantation. Although newer therapy for hepatitis B is being evaluated in adults, current therapy for children is not curative, indicating the need for lifelong therapy and potential necessity for liver transplantation. The recent epidemic of acute hepatitis in children across the world has highlighted the importance of understanding the etiology of unusual causes for acute liver failure and the urgent need for liver transplantation.

Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.

Global burden of liver disease: 2023 update.

Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.

Regular Aspirin Use Is Associated with a Reduced Risk of Hepatocellular Carcinoma (HCC) in Chronic Liver Disease: a Systematic Review and Meta-analysis.

PURPOSE: Aspirin reduces the incidence of various gastrointestinal (GI) malignancies. This meta-analysis assessed the efficacy and safety of regular aspirin use on the incidence of hepatocellular carcinoma (HCC) in patients with chronic liver disease. METHODS: Electronic reference databases were searched for studies in patients with chronic liver disease exposed to aspirin. The primary outcome was the incidence of HCC in regular aspirin users compared to non-users. The secondary outcome was the incidence of major GI bleeding events in both groups. The propensity score (PS) and non-PS-adjusted pooled hazard ratio (HR) were calculated using random-effects models. RESULTS: Six observational studies with 71,211 subjects were included. The median duration of follow-up ranged from 2.7 to 7.9 years. Four studies included patients with viral hepatitis; five studies used aspirin 100 mg/day. All six studies reported the non-PS-matched HR, and there was a 54% reduction in the incidence of HCC among regular aspirin users [HR (95% CI): 0.46(0.31-0.67), p < 0.001]. Four studies reported on the PS-matched HR; this showed a 46% reduced incidence of HCC in those using aspirin [HR (95% CI): 0.54(0.38-0.79), p < 0.001]. Subgroup analysis on studies restricted to viral hepatitis (n = 4) showed a 28% reduction in HCC incidence in aspirin users [HR (95% CI): 0.72(0.64-0.80), p < 0.001]. Four studies reported the incidence of major GI bleeds, there was no significant difference between the two groups [HR (95% CI: 1.00(0.69-1.45), p = 0.90]. All outcome analysis, except the subgroup analysis, had significant inter-study heterogeneity. CONCLUSION: Regular aspirin use in chronic liver disease is associated with reduced incidence of HCC without increasing the risk of major GI bleeding.

Prevalence and risk factors for chronic kidney disease in Indonesia: An analysis of the National Basic Health Survey 2018.

Background: The prevalence of chronic kidney disease (CKD) in Indonesia is rising, but the exact extent of the burden of CKD in Indonesia is unknown. To design a screening program for individuals at high-risk, more knowledge is required regarding the prevalence and risk factors of CKD in Indonesia. The latter could have a big impact on the prevention and management of patients with CKD in Indonesia. Methods: For this purpose, we analysed data from The National Basic Health Survey 2018 (Riset Kesehatan Dasar, Riskesdas 2018), a descriptive cross-sectional study in 34 provinces, 416 districts and 98 cities in Indonesia. We included subjects aged ≥18 years and analysed the prevalence of CKD. Using multiple logistic regression, we investigated the association between CKD and potential risk factors such as demographic factors (age, gender, occupational status, level of education), lifestyle and behaviours (consumption of salty food, consumption of fruit and vegetables, smoking, alcohol consumption, carbonated drink consumption, physical activity), comorbid conditions (hypertension, heart disease, diabetes mellitus, hepatitis, stroke, nutritional status) and others (clean water supply, pregnancy complication, access to health care). Results: We included 389 093 subjects in this study out of 713 783 subjects that participated in Riskesdas 2018 survey. The prevalence of CKD was 0.5%. The survey included mostly younger adults age 18-59 years (83.1%) with a mean (SD) age of 44.3 (15.1) years. The majority of subjects were female (60.3%), unemployed (58.4%), and the proportion of obese subject was 25.4%. Hypertension was the major comorbid condition (40.8%), while the proportion of diabetes mellitus (DM), heart disease, stroke and hepatitis were quite low (3.3%, 2.6%, 1.7% and 0.5%; respectively). Despite the high proportion of hypertension, only 36.2% of subjects did receive a prescription for anti-hypertensive medication of which only 21.7% used this medication regularly. The multiple logistic regression analysis demonstrated that hepatitis was the strongest risk factor of CKD (odds ratio (OR) = 3.406; 95% confidence interval (CI) = 2.496-4.648), exceeding the risk of CKD in patients with physical inactivity (OR = 1.236; 95% CI = 1.128-1.354), low education status (OR = 1.307; 95% CI = 1.191-1.434), male (OR = 1.527; 95% CI = 1.398-1.668), stroke (OR = 1.916; 95% CI = 1.570-2.338), heart disease (OR = 2.941; 95% CI = 2.356-3.671), and DM (OR = 2.462; 95% CI = 1.979-3.063). We also observed that DM (OR = 4.280; 95% CI = 3.756-4.876) and male subjects (OR = 1.474; 95% CI = 1.352-1.606) were identified as independent risk factors for CKD in hepatitis-positive subjects. Conclusions: This population-based survey confirmed the increasing burden of CKD in Indonesia and suggested that besides traditional metabolic risk factors, viral hepatitis has proven to be an independent risk factor for CKD in Indonesia. Furthermore, the risk of CKD is greater in male hepatitis patients with DM. The result of this study demonstrates the need for an aggressive screening program for patients with a high risk for the development of CKD. Apart from patients with traditional cardiometabolic risk factors, such a program should include patients with viral hepatitis.

Gaps in hepatocellular carcinoma surveillance in a United States cohort of insured patients with cirrhosis.

OBJECTIVE: Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. METHODS: We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 through June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥ 6-month follow-up. RESULTS: Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11-2.17, p = .010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77-4.09, p < .001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002-1.351] vs 0.880 [0.796-0.972]; viral hepatitis, 2.688 [1.765-4.093] vs 1.553 [1.111-2.171]; Other, 0.612 [0.519-0.722] vs 0.549 [0.470-0.641]). Mean total and patient-paid daily surveillance-related costs ranged from $540 and $113, respectively (ultrasound) to $1580 and $300, respectively (magnetic resonance imaging), and mean estimated patient productivity costs were $730-$2514 annually. CONCLUSION: HCC surveillance was underutilized and was lowest among patients with nonviral etiologies and those who had not seen a gastroenterologist. Surveillance-related out-of-pocket expenses and lost productivity were substantial. The development of surveillance strategies that reduce patient burden, such as those using blood-based biomarkers, may help improve surveillance adherence and effectiveness.

Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment.

Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.

[Liver and colonic manifestation of active chronic infection by Epstein Barr virus]. / Manifestación hepática y colónica de la infección crónica activa por virus de Epstein Barr.

INTRODUCTION: Chronic active Epstein Barr virus infection (CAEBV) is a rare condition, where the body is unable to counteract Epstein Barr viral replication (EBV), leading the patient to a chronic state with variable symptoms. Early recognition of infrequent or atypical clinical manifestations is relevant due to the particularities of their management and prognosis. OBJECTIVE: to describe a case of CAEBV manifes ted with colitis and hepatitis, summarizing the clinical-pathological and endoscopic characteristics and their evolution. CLINICAL CASE: A 6-year-old girl, previously healthy, presented recurrent episodes of jaundice, hepatosplenomegaly, and fever. EBV hepatitis was diagnosed with a blood viral load of 328,000 copies / mL. Her liver biopsy revealed Epstein-Barr virus-encoded small RNAs (EBER). She evolved with mucosanguineous diarrhea and weight loss; the colonoscopy showed loss of the haustral pattern, multiple aphthous ulcers covered with fibrin, and 7 million copies of EBV / gram of tissue were found in the colon. T-cell lineage infection was identified, therefore Rituximab was started, with a decrease in viral load, complete resolution of diarrhea, and improvement in liver function tests. The definitive treatment was bone marrow transplantation. CONCLUSIONS: CAEBV is a serious disor der, little documented, and should be considered in the face of a prolonged or intermittent course of hepatitis, accompanied by general and gastrointestinal manifestations such as chronic diarrhea, hematochezia, and weight loss, since its outcome without treatment can be fatal.

Liver cancer and hepatic decompensation events in patients hospitalized with viral hepatitis in Spain.

BACKGROUND: Chronic viral hepatitis B, C, and D are the main causes of decompensated cirrhosis and liver cancer worldwide. Newborn HBV vaccination was implemented more than 2 decades ago in most EU countries. Furthermore, potent oral antivirals have been available to treat HBV for 15 years and to cure HCV since 2014. The real-life clinical benefits of these interventions at country level have not been assessed, especially regarding major hepatic outcomes such as cirrhotic decompensation events and hepatocellular carcinoma (HCC). METHODS: Retrospective study of all hospitalizations in Spain having HBV, HCV, and HDV as diagnosis using the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 up to 2017. RESULTS: From a total of 73,939,642 hospital admissions during the study period, a diagnosis of HBV, HCV, and HDV was made in 124,915 (1.7‰), 981,985 (13.3‰), and 4850 (0.07‰) patients, respectively. The median age of patients hospitalized within each group was 53.2, 55.9, and 47.0 years, respectively. Significant increases in mean age at hospitalization occurred in all groups (0.6 years older per calendar year on average). The overall rate of hepatic decompensation events for HBV, HCV, and HDV was 12.1%, 14.1%, and 18.8%, respectively. For HCC hospitalizations, these figures were 6.7%, 8.0%, and 7.8%, respectively. Whereas, the rate of decompensation events declined in recent years for HBV, and more recently for HCV, it continued rising up for HDV. Likewise, liver cancer rates recently plateaued for HBV and HCV, but kept growing for HDV. CONCLUSION: The rate of hepatic decompensation events and liver cancer has declined and/or plateaued in recent years for patients hospitalized with HBV and HCV infections, following the widespread use of oral antiviral therapies for these viruses. In contrast, the rate of decompensated cirrhotic events and HCC has kept rising up for patients with hepatitis delta, for which effective antiviral treatment does not exist yet.

Association of statin treatment with hepatocellular carcinoma risk in end-stage kidney disease patients with chronic viral hepatitis.

Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42-0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, - 3.7; 95% CI - 5.7 to - 1.7; P < 0.001). Incidence rate ratio (IRR) was also consistent with other analyses (IRR, 0.56; 95% CI, 0.41 to 0.78; P < 0.001). Statin use was associated with a lower risk of incident HCC in dialysis patients with chronic hepatitis B or C infection.

Two differentially methylated region networks in nonalcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma.

BACKGROUND: We previously reported that two differentially methylated region (DMR) networks identified by DMR and co-methylation analyses are strongly correlated with the fibrosis stages of nonalcoholic fatty liver disease (NAFLD). In the current study, we examined these DMR networks in viral hepatitis and hepatocellular carcinoma (HCC). METHODS: We performed co-methylation analysis of DMRs using a normal dataset (GSE48325), two NAFLD datasets (JGAS000059 and GSE31803), and two HCC datasets (GSE89852 and GSE56588). The dataset GSE60753 was used for validation. RESULTS: One DMR network was clearly observed in viral hepatitis and two HCC populations. Methylation levels of genes in this network were higher in viral hepatitis and cirrhosis, and lower in HCC. Fatty acid binding protein 1 (FABP1), serum/glucocorticoid regulated kinase 2 (SGK2), and hepatocyte nuclear factor 4 α (HNF4A) were potential hub genes in this network. Increased methylation levels of the FABP1 gene may be correlated with reduced protection of hepatocytes from oxidative metabolites in NAFLD and viral hepatitis. The decreased methylation levels of SGK2 may facilitate the growth and proliferation of HCC cells. Decreased methylation levels of HNF4A in HCC may be associated with tumorigenesis. The other DMR network was observed in NAFLD, but not in viral hepatitis or HCC. This second network included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation, which are specifically related to fibrosis and/or tumorigenesis in NAFLD. CONCLUSIONS: Our results suggest that one DMR network was associated with fibrosis and tumorigenesis in both NAFLD and viral hepatitis, while the other network was specifically associated with NAFLD progression. Furthermore, FABP1, SGK2, and HNF4A are potential candidate targets for the prevention and treatment of HCC.

Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease.

Advanced liver diseases account for approximately 2 million deaths annually worldwide. Roughly, half of liver disease-associated deaths arise from complications of cirrhosis and the other half driven by viral hepatitis and hepatocellular carcinoma. Unfortunately, the development of therapeutic strategies to treat subjects with advanced liver disease has been hampered by a lack of mechanistic understanding of liver disease progression and a lack of human-relevant animal models. An important advance has been made within the past several years, as several genome-wide association studies have discovered that an SNP near the gene encoding membrane-bound O-acyltransferase 7 (MBOAT7) is associated with severe liver diseases. This common MBOAT7 variant (rs641738, C>T), which reduces MBOAT7 expression, confers increased susceptibility to nonalcoholic fatty liver disease, alcohol-associated liver disease, and liver fibrosis in patients chronically infected with viral hepatitis. Recent studies in mice also show that Mboat7 loss of function can promote hepatic steatosis, inflammation, and fibrosis, causally linking this phosphatidylinositol remodeling enzyme to liver health in both rodents and humans. Herein, we review recent insights into the mechanisms by which MBOAT7-driven phosphatidylinositol remodeling influences liver disease progression and discuss how rapid progress in this area could inform drug discovery moving forward.

Peritumoral histopathologic findings in patients with chronic viral hepatitis-associated hepatocellular carcinoma.

Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)-associated HCC (CVH-HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH-HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39-67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence-free survival in both uni- and multivariate analysis. Peritumoral histopathologic changes in CVH-HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.

Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.

Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and D, although these diseases are caused by very different viruses. Paired with the conventional study of protein-host interactions, the rapid technological development of -omics and bioinformatics has allowed highlighting the important role of signaling networks in viral pathogenesis. In this review, we provide an integrated look on the three major viruses associated with chronic viral hepatitis in patients, summarizing similarities and differences in virus-induced cellular signaling relevant to the viral life cycles and liver disease progression.