Non-viral Liver Disease Research Articles

Chronic non-viral liver pathology in military personnel exposed to military-professional factors

Abstract. The prevalence and structure of chronic non-viral liver disease of military personnel whose service is associated with the influence of various military-professional factors are estimated. It is established that the frequency of chronic diffuse liver diseases of viral etiology in a group of servicemen radio-technical troops was 77,3%, from persons engaged in diving and altitude descents 65,9%, pilots of the aerospace defence forces of Russia 62,8%, in persons without exposure to military occupational factors is 69,5%. The largest number of persons suffering from chronic non-viral liver disease in the group of military radio-technical troops, probably related to low levels of physical activity and higher values of body mass index and waist circumference, but also the influence of microwave radiation, can enhance the damaging effects of lipid peroxidation. The lowest prevalence of non-viral chronic diffuse liver diseases among pilots and aquanauts is probably related to the maximum health requirements imposed on military personnel of these categories. It was found that the level of alcohol consumption and the nature of nutrition in the study groups did not significantly differ. The highest values of body mass index and waist circumference in combination with the lowest level of physical activity were observed in the group of military personnel of the radio engineering troops, which is probably due to the nature of daily military service, which is mainly sedentary. Among the metabolic changes of blood serum, increased total cholesterol levels in groups of divers, pilots and military Radio-technical troops compared with a control. In addition, the level of glucose in Aquanauts, as well as triglycerides in soldiers of the radio engineering troops was higher than in the control group. Ultrasound examination in all groups related to the impact of military occupational factors, recorded an increase in the thickness of the left lobe of the liver, and oblique vertical size and thickness of the right lobe in the group of soldiers of the radio-technical troops compared with a control. In addition, the values of the thickness of the intima-media complex as a marker of preclinical atherosclerosis associated with non-alcoholic and alcoholic-metabolic fatty liver diseases in this category of individuals significantly exceed them in the other groups. The maximum level of liver damage in the group of military personnel of radio engineering troops is confirmed by the highest values of the controlled parameter of attenuation of ultrasound, reflecting the degree of liver steatosis.

Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients.

BACKGROUNDReliable biomarkers of cirrhosis, hepatocellular carcinoma (HCC), or progression of chronic liver diseases are missing. In this context, Golgi protein-73 (GP73) also called Golgi phosphoprotein-2, was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells. As a result, GP73 expression was found primarily in biliary epithelial cells, with only slight detection in hepatocytes. However, in patients with acute or chronic liver diseases and especially in HCC, the expression of GP73 is significantly up-regulated in hepatocytes. So far, few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIMTo assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODSGP73 serum levels were retrospectively determined by a novel GP73 ELISA (QUANTA Lite® GP73, Inova Diagnostics, Inc., Research Use Only) in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa, Greece (n = 366) and Debrecen, Hungary (n = 266). Aspartate aminotransferase (AST)/Platelets (PLT) ratio index (APRI) was also calculated at the relevant time points in all patients. Two hundred and three patients had chronic hepatitis B, 183 chronic hepatitis C, 198 alcoholic liver disease, 28 autoimmune cholestatic liver diseases, 15 autoimmune hepatitis, and 5 with other liver-related disorders. The duration of follow-up was 50 (57) mo [median (interquartile range)]. The development of cirrhosis, liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines. In particular, the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein (AFP) determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTSIncreased serum levels of GP73 (> 20 units) were detected at initial evaluation in 277 out of 632 patients (43.8%). GP73-seropositivity correlated at baseline with the presence of cirrhosis (96.4% vs 51.5%, P < 0.001), decompensation of cirrhosis (60.3% vs 35.5%, P < 0.001), presence of HCC (18.4% vs 7.9%, P < 0.001) and advanced HCC stage (52.9% vs 14.8%, P = 0.002). GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score [Area under the curve (AUC) (95%CI): 0.909 (0.885-0.934) vs 0.849 (0.813-0.886), P = 0.003]. Combination of GP73 with APRI improved further the accuracy (AUC: 0.925) compared to GP73 (AUC: 0.909, P = 0.005) or APRI alone (AUC: 0.849, P < 0.001). GP73 levels were significantly higher in HCC patients compared to non-HCC [22.5 (29.2) vs 16 (20.3) units, P < 0.001) and positively associated with BCLC stage [stage 0: 13.9 (10.8); stage A: 17.1 (16.8); stage B: 19.6 (22.3); stage C: 32.2 (30.8); stage D: 45.3 (86.6) units, P < 0.001] and tumor dimensions [very early: 13.9 (10.8); intermediate: 19.6 (18.4); advanced: 29.1 (33.6) units, P = 0.004]. However, the discriminative ability for HCC diagnosis was relatively low [AUC (95%CI): 0.623 (0.570-0.675)]. Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline, was prognostic of higher rates of decompensation (P = 0.036), HCC development (P = 0.08), and liver-related deaths (P < 0.001) during follow-up.CONCLUSIONGP73 alone appears efficient for detecting cirrhosis and superior to APRI determination. In combination with APRI, its diagnostic performance can be further improved. Most importantly, the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and non-viral chronic liver diseases.

1000P Trends of characteristics, treatment and prognosis of hepatocellular carcinoma in Japan during the last decade

From the 1980s to 2009, prognosis of hepatocellular carcinoma (HCC) in Japan had been improved. Since then, additional treatment modalities have become available. At the same time, we are facing a new problem of rapid increase of non-viral HCC. Here we investigated the trends of clinical characteristics, treatment strategy and prognosis of HCC during the last decade. A total of 1184 patients with newly diagnosed and recurrent HCC treated in Kurashiki Central Hospital between Jan 2009 and Dec 2018 were retrospectively analyzed. The cohort was categorized into four groups according to the treatment period; Jan 2009–Jun 2011 (period 1, N = 487), Jul 2011–Dec 2013 (period 2, N = 468), Jan 2014–Jun 2016 (period 3, N = 382) and Jul 2016–Dec 2018 (period 4, N = 366). Among them, major treatment procedure and use of molecular targeted agents (MTA) were compared by using the Cochran-Amitage test. Evaluated treatment procedures were; surgery, radiofrequency ablation (RFA), stereotactic body radiotherapy (SBRT), transarterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy. We also compared clinical characteristics and survival time between patients with newly diagnosed HCC in period 1(N = 217) and period 4 (N = 173) by using the Fisher’s exact test and the log-rank tests, respectively. As treatment procedure, RFA and TACE significantly decreased, whereas surgery, SBRT, and start of MTA increased during the last decade. In comparison between period 1 and 4, none of age, sex, BCLC stage or Child–Pugh score was significantly different. Regarding the etiology of underlying liver diseases, hepatitis C decreased and non-viral liver diseases increased significantly (p<.001). In the survival time, no significant difference was found (p=.894), even after stratification by their BCLC stage (p=.672) or Child–Pugh class (p=.191). During the last decade, the treatment for HCC has changed significantly, but the prognosis of HCC has not apparently been improved. In addition, the significant shift of causes for HCC to non-viral liver diseases was noted. Taken together, our findings indicate importance of future intervention for prevention and early detection of non-viral liver diseases to overcome HCC.

Possibilities of transient and two-dimensional shear wave elastography in the diagnosis of fibrosis in nonviral chronic diffuse liver diseases in military personnel

The study examines the possibilities of transient and two-dimensional shear wave elastography in the diagnosis of fibrosis in the most common chronic diffuse liver diseases of non-viral etiology: alcoholic and non-alcoholic fatty liver disease, as well as their combination. It was found that in patients suffering from these diseases, the values of aspartate and alanine aminotransferase, gamma-glutamyl transpeptidase, cholesterol, triglycerides, as well as the oblique vertical size of the right lobe of the liver were significantly (p0,05) higher than in patients of the control group. Moreover, most of these indicators reliably (p0,01) reached the highest values in patients suffering from fatty liver disease of alcohol-metabolic etiology, which confirms a more pronounced damaging effect on the liver with a combination of alcohol and metabolic factors. It has been established that the use of transient and two-dimensional elastography is characterized by high diagnostic significance in determining the stage of fibrosis in chronic diffuse liver diseases of non-viral etiology. The greatest diagnostic significance of elastographic research methods is noted in the third and fourth stages of fibrosis. In the second stage of fibrosis, the quality of diagnostic significance when using transient elastography was higher than when using two-dimensional shear wave. The use of transient and two-dimensional shear wave elastography in most cases avoids liver biopsy in patients suffering from chronic diffuse liver diseases of non-viral etiology. Therefore, in the diagnosis of chronic diffuse liver diseases, the presence and degree of fibrosis is a factor that will largely determine the prognosis, treatment tactics and the likelihood of complications in a particular patient.

The diagnostic accuracy of liver fibrosis in non-viral liver diseases using acoustic radiation force impulse elastography: A systematic review and meta-analysis.

BackgroundAcoustic radiation force impulse (ARFI) imaging is an ultrasound-based elastography method that has been studied in the staging of hepatic fibrosis, especially in chronic hepatitis. However, the diagnostic accuracy of ARFI in non-viral hepatopathies, such as autoimmune hepatitis and non-alcoholic fatty liver disease, has not been systematically determined.AimTo systematically assess the diagnostic accuracy of ARFI in non-viral hepatopathies.MethodsThe databases of PubMed, Embase, Cochrane Library and clinicaltrials.gov were systematically searched for candidate studies reporting the diagnostic accuracy of ARFI for hepatic fibrosis. The pooled estimates of the sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios were calculated with the summary receiver operating curve (sROC) performed using STATA software.ResultsIn detail, a total of 29 diagnostic studies were included for further analysis. The quality of the included studies was relatively high using QUADAS method. The pooled sensitivity and specificity were 0.79 (0.73, 0.83) and 0.81 (0.75, 0.86), with AUROC 0.87 (0.83, 0.89) for the staging of significant fibrosis (F≥2). Meanwhile, for the staging of severe fibrosis (F≥3), the pooled sensitivity and specificity were 0.92 (0.87, 0.95) and 0.85 (0.80, 0.89), with AUROC 0.94 (0.92, 0.96). Furthermore, the pooled sensitivity and specificity were 0.89 (0.79, 0.95) and 0.89 (0.85, 0.92), with AUROC 0.94 (0.92, 0.96) for ARFI in staging cirrhosis (F = 4), which were similar to the data for severe fibrosis. No significant publication bias was present in this study.ConclusionThis meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in staging non-viral hepatic fibrosis, especially severe fibrosis (F≥3) and cirrhosis (F = 4).

Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies.

Coexistence of alcohol use and metabolic risk-the 2 commonest population risk factors for nonviral chronic liver disease-is a growing concern. Clinical evidence and mechanistic evidence point to considerable supraadditive interaction effects for the development and progression of chronic liver disease between hazardous alcohol use and metabolic abnormalities including obesity, diabetes, and the metabolic syndrome (MetS). Intermittent binge drinking once monthly or more often seems to be associated with progression of liver disease even when average alcohol intake is within the currently allowed limits for a diagnosis of nonalcoholic fatty liver disease (NAFLD), and supraadditive interaction between binge drinking and the MetS has been reported. There are contradictory findings regarding the association between low alcohol use and liver steatosis, but, clearly, the mechanisms of alcoholic hepatotoxicity extend beyond simple fat accumulation. The presence of liver steatosis seems to amplify alcoholic hepatotoxicity. Recent longitudinal studies of NAFLD subjects report low alcohol use associated with both increased fibrosis progression and an elevated risk for liver cancer and severe liver disease. There is no clear safe limit of alcohol intake in the presence of NAFLD or metabolic risk. The interaction effects between alcohol and metabolic dysfunction merit increased attention in public health policy, individual counseling, and risk stratification. Based on current evidence, a strict dichotomization of liver disease into either pure alcoholic or nonalcoholic may be inappropriate.

Non-viral liver diseases: pathogenetic approaches to therapy

Alcoholic liver disease and non-alcoholic fatty liver disease are chronic non-communicable diseases with an extremely high prevalence among the world's population. Currently, there is a tendency to a rapid increase in their number with frequent disability of patients and a high need for liver transplantation. Violations of the main metabolic processes in the liver under the influence of exogenous and endogenous factors are the starting point in the development of alcoholic and nonalcoholic liver pathology. This review discusses the main recommendations for non-drug and drug management of patients with liver diseases of non-viral etiology with a detailed description of the main hepatoprotectors with an emphasis on the universal properties of silymarin.

Effect of sample type and storage conditions on Golgi membrane protein 73 stability

GP73 is a transmembrane glycoprotein that increases in viral and non-viral liver diseases, especially in hepatocellular carcinoma. This study aims to evaluate the effect of sample type and storage conditions on GP73 concentration. Twenty subjects were enrolled in this study. Serum and citrated plasma samples were collected. Both were subjected to different time intervals and storage temperature. Baseline GP73 concentrations ranged from 1.7 to 16.9 ng/mL in serum samples, and from 1.1 to 15.3 ng/mL in citrated plasma (Mann–Whitney U test, p = .1). The acceptable change limit for GP73 was 6.1%. As the highest value of the median percentage deviation was −5.3% in both sample types at different storage condition so, deviations were within the accepted limits. But there were considerable variations in the GP-73 concentrations after 2 cycles of freezing and thawing at −20 °C. This study shows that both serum and citrated plasma can be used for the measurement of GP73 concentration. GP73 seems to be stable under common storage conditions, but it may be unstable with frequent cycles of freezing and thawing.

Genetic and lifestyle risk factors for advanced liver disease among men and women.

Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. A total of 355 liver events occurred during the mean 12.4-year follow-up (511789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P=0.0083 for men; HR 1.04, P=0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P=0.0006 for men; HR 1.58, P=0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P=0.024 for men; HR 2.7, P=0.0109 for women), and weekly binge drinking (HR 2.4, P=0.0024 for men; HR 7.4, P<0.0001 for women) predicted development of severe liver disease. Among men, diabetes (HR 2.7, P=0.0002), average alcohol consumption (HR for 10g/day 1.1, P=0.0022), non-married status (HR 1.9, P=0.0397 for single; HR 2.4, P=0.0002 for widowed/separated), and serum high-density lipoprotein (HR 2.2, P=0.0022) and non-high-density lipoprotein cholesterol (HR 1.2, P=0.0237) were additional risk factors. Alcohol intake increased the risk especially among persons with high WHR (P for interaction 0.009). Age, patatin-like phospholipase-containing domain 3 haplotype, and WHR increase the risk for development of severe liver disease. We found strong synergism between alcohol and central obesity. Binge drinking is an additional risk factor.

Baseline risk factors determine lack of biochemical response after SVR in chronic hepatitis C patients treated with DAAs.

Liver function tests (alanine aminotransferase, ALT; gamma-glutamyltransferase, GGT) not always normalize after elimination of hepatitis C virus (HCV) by direct acting antivirals (DAAs), possibly indicating concomitant non-viral liver diseases. We analysed factors determining the biochemical response (normalized ALT/GGT) of DAA therapy in a large real-world cohort. The German Hepatitis C-Registry is a national multicenter registry study. Normal ALT was defined ≤35U/L (female) and ≤50U/L (male) or, according to AASLD, ≤19U/L (female) and ≤30U/L (male), normal GGT ≤40U/L (female) and ≤60U/L (male). At baseline, ALT was elevated in 3705/4946 (74.9%), ALT (AASLD) in 4669/4946 (94.4%) and GGT in 3018/4906 (61.5%). In this study, 97% of patients achieved SVR12. At week 12 after end of therapy, ALT was elevated in 451/4946 (9.1%), ALT according to AASLD in 1906/4946 (38.5%) and GGT in 863/4879 (17.7%). Persistently elevated ALT after DAA therapy was independently associated with high body mass index (BMI), age <70years, liver cirrhosis, diabetes, alcohol consumption and not achieving SVR12. Using the stricter AASLD criteria, opioid substitution and male sex were additional predictors. Higher GGT at week 12 was associated with high BMI, age >70years, liver cirrhosis, diabetes, alcohol consumption, opioid substitution and non-SVR. Importantly, persistently elevated liver tests after treatment, particularly GGT, were associated with hepatic decompensation and mortality during 4-years follow-up. Risk factors at baseline (obesity, diabetes, liver cirrhosis, alcohol consumption) are independently associated with persistently elevated liver function tests after SVR, indicating that these patients warrant further hepatological follow-up. German Clinical Trials Register (DRKS; ID DRKS00009717).

Development and validation of a prediction model to estimate the risk of liver cirrhosis in primary care patients with abnormal liver blood test results: protocol for an electronic health record study in Clinical Practice Research Datalink

BackgroundDriven by alcohol consumption and obesity, the prevalence of non-viral liver disease in the UK is increasing. Due to its silent and slow nature, the progression of liver disease is currently unpredictable and challenging to monitor. The latest National Institute for Health Care Excellence cirrhosis guidelines call for a validated risk tool that would allow general practitioners to identify patients that are at high risk of developing cirrhosis.MethodsUsing linked electronic health records from the Clinical Practice Research Datalink (a database of > 10 million patients in England), we aim to develop and validate a prediction model to estimate 2-, 5- and 10-year risk of cirrhosis. The model will provide individualised cirrhosis risk predictions for adult primary care patients, free from underlying liver disease or viral hepatitis infection, whose liver blood test results come back abnormal. We will externally validate the model in patients from 30 further Clinical Practice Research Datalink general practices in England.DiscussionThe prediction model will provide estimates of cirrhosis risk in primary care patients with abnormal liver blood test results to guide referral to secondary care, to identify patients who are in serious need of preventative health interventions and to help reassure patients at low risk of cirrhosis in the long term.

Interferon Lambda and Liver Fibrosis.

Fibrosis is a highly conserved and coordinated wound healing response to injury. In the liver, injury is promoted by immune effector mechanisms that are common across various disease etiologies and even between organs such as lungs, kidneys, heart, and other organs. Thus, the liver represents a useful model to study inflammation and repair, particularly as it is frequently biopsied in clinical contexts. Currently, strong evidence implicates IFNL3/4 polymorphisms and interferon (IFN)-λ3 levels as determinants of the extent of hepatic inflammation and fibrosis in viral and nonviral liver diseases, as well as in governing the severity of nonhepatotropic viral diseases. Interestingly, IFNL3/4 polymorphisms and IFN-λ3 levels correlate with fibrosis extent in other organs such as the lung and kidney. In this review, we discuss the association between IFN-λ and tissue inflammation and fibrosis in human disease and the potential clinical utility of the findings.

Aspirin: Does it Have a Role for Chemoprevention of Hepatocellular Carcinoma?

Aspirin: Does it Have a Role for Chemoprevention of Hepatocellular Carcinoma?

Outcomes of immunosuppression minimization and withdrawal early after liver transplantation.

The Immune Tolerance Network ITN030ST A-WISH assessed immunosuppression withdrawal in liver transplant recipients with hepatitis C or nonimmune nonviral liver disease. Of 275 recipients enrolled before transplantation, 95 were randomly assigned 4:1 to withdrawal (n=77) or maintenance (n=18) 1- to 2-years posttransplant. Randomization eligibility criteria included stable immunosuppression monotherapy; adequate liver and kidney function; ≤Stage 2 Ishak fibrosis; and absence of rejection on biopsy. Immunosuppression withdrawal followed an 8-step reduction algorithm with ≥8weeks per level. Fifty-two of 77 subjects (67.5%) reduced to ≤50% of baseline dose, and 10 of 77 (13.0%) discontinued all immunosuppression for ≥1year. Acute rejection and/or abnormal liver tests were treated with increased immunosuppression; 5 of 32 rejection episodes required a methylprednisolone bolus. The composite end point (death or graft loss; grade 4 secondary malignancy or opportunistic infection; Ishak stage ≥3; or >25% decrease in glomerular filtration rate within 24months of randomization) occurred in 12 of 66 (18%) and 4 of 13 (31%) subjects in the withdrawal and maintenance groups. Early immunosuppression minimization is feasible in selected liver recipients, while complete withdrawal is successful in only a small proportion. The composite end point comparison was inconclusive for noninferiority of the withdrawal to the maintenance group.

Relationship between genetic variation at PPP1R3B and levels of liver glycogen and triglyceride.

These observations are consistent with the notion that the minor allele of rs4841132 promotes a mild form of hepatic glycogenosis that is associated with hepatic injury. (Hepatology 2018;67:2182-2195).

Soluble intercellular adhesion molecule-1 is associated with hepatocellular carcinoma risk: multiplex analysis of serum markers

Individualized assessment of hepatocellular carcinoma (HCC) risk in chronic liver disease remains challenging. Serum biomarkers including cytokines may offer helpful adjuncts to standard parameters for risk prediction. Our aim was to identify markers associated with increased HCC incidence. This was a prospective cohort study of 282 patients with both viral or non-viral chronic liver disease. Baseline serum cytokines and other markers were measured in multiplex with a commercially-available Luminex-based system. Patients were followed until death or HCC diagnosis. We performed Lasso-based survival analysis to determine parameters associated with HCC development. Cytokine mean florescence intensity (MFI) was the primary predictor and HCC development the primary outcome. 25 patients developed HCC with total follow-up of 1,363 person-years. Parameters associated with increased HCC incidence were cirrhosis, hepatic decompensation, and soluble serum intercellular adhesion molecule 1 (sICAM-1) MFI. No other molecules increased predictive power for HCC incidence. On univariate analysis, the parameters associated with HCC incidence in patients with cirrhosis were age, antiviral treatment, and high sICAM-1 MFI; on multivariate analysis, sICAM-1 remained associated with HCC development (adjusted HR = 2.75). On unbiased screening of serum cytokines and other markers in a diverse cohort, baseline sICAM-1 MFI is associated with HCC incidence.

Zinc is a potent and specific inhibitor of IFN-\u03bb3 signalling

Lambda interferons (IFNL, IFN-λ) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels. Zinc interferes with IFN-λ3 binding to IFNL receptor 1 (IFNLR1), resulting in decreased antiviral activity and increased viral replication (HCV, influenza) in vitro. HCV patients with high zinc levels have low hepatocyte antiviral and inflammatory gene expression and high viral loads, confirming the inhibitory role of zinc in vivo. We provide the first evidence that zinc can act as a potent and specific inhibitor of IFN-λ3 signalling and highlight its potential as a target of therapeutic intervention for IFN-λ3-mediated chronic disease.

Research advances in autoimmune liver diseases in 2016

Autoimmune liver diseases are a group of abnormal autoimmune-mediated inflammatory hepatobiliary injuries, mainly including autoimmune hepatitis(AIH), primary biliary cholangitis(PBC), and primary sclerosing cholangitis (PSC). The diagnosis and treatment of autoimmune liver diseases, an important type of non-viral liver disease, have become a prominent issue in hepatology. In 2016, many new advances have been achieved in the clinical and basic research on autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, the proposal of UK-PBC risk score, and the research on gut microbiota associated with PSC. This article reviews the research advances in the diagnosis and treatment of autoimmune liver diseases in 2016.

Patients with non-viral liver disease have a greater tumor burden and less curative treatment options when diagnosed with hepatocellular carcinoma.

AIMTo assess the impact of underlying liver disease etiology on the presenting features and outcomes in a large cohort of patients with hepatocellular carcinoma (HCC).METHODSA prospective database of all patients with HCC was established from 1998 to March 2012. One thousand and seventy-eight patients were categorized into three groups, based on the etiology of their liver disease: hepatitis B virus (HBV), hepatitis C virus (HCV) and non-viral liver disease (NVLD). Overall survival was determined by Kaplan Meier analysis to time of death or last follow-up.RESULTSHCC patients with HCV (85%) were more likely to be diagnosed as part of a surveillance program, compared to HBV or NVLD (both 71%) (P < 0.001). Patients with NVLD were more likely to receive best supportive care (29%) compared to those with HBV (21%) or HCV (20%) (P < 0.02). Twelve percent of NVLD and 13% of HBV patients underwent liver transplantation compared to 21% of HCV patients (P = 0.001). Median survival from presentation was lowest in NVLD (1.7 years) when compared to HBV (2.8 years) and HCV (2.6 years) (P < 0.05). In multivariate analysis, independent predictors of survival included Child Turcotte Pugh score, size of dominant lesion, absence of vascular invasion, and management with surgical resection or liver transplantation. Patient age and the etiology of the underlying liver disease were not independent predictors of survivalCONCLUSIONPatients with NVLD and HCC were less likely to be enrolled in a HCC surveillance program and are less likely to have curative therapies such as liver resection and transplantation after diagnosis with HCC, when compared to patients with Hepatitis B and Hepatitis C.

Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, is involved in cell proliferation, inflammation and remodeling of the extracellular matrix. The aim of this study was to assess whether serum YKL-40 levels are associated with liver fibrosis in NAFLD patients. Serum YKL-40 levels were quantified in 111 NAFLD patients and 23 HCC patients with NAFLD. To identify the source of YKL-40, immunofluorescence staining of liver specimens from NAFLD patients was performed. Serum YKL-40 levels in NAFLD patients increased in accordance with the progression of liver fibrosis. Multivariate analysis revealed that YKL-40 was one of the independent factors significantly associated with severe fibrosis (F3-4). We established a new predictive model for fibrosis of NAFLD, using logistic regression analysis: YKL-40 based fibrosis score = −0.0545 + type IV collagen 7s * 0.3456 + YKL-40 * 0.0024. Serum YKL-40 levels of HCC patients with non-cirrhotic NAFLD were significantly higher than those without HCC. Immunofluorescence staining showed that YKL-40 was expressed by macrophages in liver tissue of NAFLD patients. In conclusion, macrophage-derived YKL-40 is a feasible biomarker of liver fibrosis in NAFLD patients.