Comparison of the efficacy of radiofrequency ablation vs. liver resection in the treatment of hepatocellular carcinoma within Milan criteria with severe fibrosis

BackgroundThe efficacy of RFA in the treatment of HCC with severe fibrosis is still unclear. The objective of this study is to compare the efficacy of RFA with liver resection in the treatment of HCC within Milan criteria.MethodsThe data used in the study were from the SEER database. Patients with HCC within Milan criteria were included in the study. A total of 1432 patients were included in the study; among them, 1038 patients received RFA, and 394 patients received liver resection. Propensity score matching (PSM) was used to reduce selection bias.ResultsBefore PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the resection group were longer than the mOS and mCSS in the RFA group. However, the8re were no statistically significant differences in mOS or mCSS between the two groups (both P>0.05). After PSM, similar results were presented, and the mOS and mCSS in the resection group were similar to those in the RFA group (both P>0.05). The multivariable Cox regression analysis showed that RFA did not increase the all-cause mortality risk and cancer-specific mortality risk compared with resection before PSM. In the competing risk analysis, after excluding the potential factors that might influence the outcomes, RFA still did not increase the mortality risk compared with resection before PSM and after PSM. In the subgroup analysis. The efficacy of RFA is comparable to that of resection in patients with tumor sizes no more than 3 cm before PSM and after PSM.ConclusionThe efficacy of RFA is similar to that of resection in the treatment of early HCC patients with severe fibrosis, especially in patients with tumor sizes no more than 3 cm.

A STUDY TO ASSESS OCCURRENCE OF NON ALCOLOHOLIC FATTY LIVER DISEASE AND LIVER FIBROSIS IN TYPE 2 DIABETES MELLITUS PATIENTS AND THE ASSOCIATED FACTORS

Background: This study aimed to evaluate the burden of NAFLD and severe fibrosis among DM population. Methods: It was a hospital based observational and cross-sectional study. Upgraded department of General Medicine, SMS Medical College andAttached Hospitals, (Jaipur). Results: Out of 100 patients 48 patients did not have NAFLD while 52 patients had NAFLD. Thus proportion of NAFLD in diabetic patients was quite high (52%). Out of 52 NAFLD patients 27 patients (51.9%) had mild liver fibrosis, 14 patients (26.9%) had significant fibrosis and 11 patients (21.2%) had severe liver fibrosis. Thus proportion of NAFLD patients with significant and severe fibrosis was quite high (26.9% and 21.2%respectively). Conclusion: From the study it can be concluded that the prevalence of NAFLD in adult patients with type 2 diabetes mellitus in department ofmedicine at S. M. S. Hospital, Jaipur is 52% and moderate and severe fibrosis is found in 26.9% and 21.2% patients respectively among them. BMI and the waist circumference are the factors in our study that have shown association with the incidence of NAFLD in type 2 DM patients. Keywords: DM, NAFLD, BMI.

Dynamics of Circulating miR-122 Predict Liver Cancer and Mortality in Japanese Patients with Histopathologically Confirmed NAFLD and Severe Fibrosis Stage

<b><i>Introduction:</i></b> It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD). <b><i>Methods:</i></b> This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years. <b><i>Results:</i></b> The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios &#x3c;0.5 (serum miR-122 level at second biopsy to that at first biopsy) than those with ratios ≥0.5. The cumulative survival rates in cases with miR-122 ratios &#x3c;0.5 tended to be lower than those with ratios ≥0.5. Of the 64 high-risk patients, 39 indicated stage 2 or greater (severe fibrosis stage) at the first liver biopsy and also showed similar results of cumulative liver cancer and survival rates. <b><i>Conclusions:</i></b> Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores.

Retinoblastoma Morphology after Local Chemotherapy

Purpose. Determine the nature of tumor regression and possible complications associated with the retinotoxic effect of melphalan and carboplatin with local chemotherapy.Methods. A histological analysis of 19 enucleated eyes from 19 patients with retinoblastoma was performed after combined organ-preserving treatment, including systemic chemotherapy and local chemotherapy in various doses. The enucleated eyes were fixed in 10 % formalin and processed routinely for histological examination.Results. Significant changes in the tumor tissue such as tumor regression associated with the destruction of the tumor tissue and its replacement with fibrous tissue, glia proliferation, and the formation of petrificates were revealed. Complete regression of the tumor was detected in 3 out of 19 eyes, partial in 13 eyes. There were no signs of regression in 3 eyes. Tumor invasion into the choroid was found in 5 cases, into the anterior sector — in 3 cases, into the optic nerve — in 3 cases. The retrobulbar tumor was presented in 1 case. Retinotoxic complications revealed. Hemorrhagic changes associated with focal necrosis of the central retinal vessels (n = 4), destructive changes in retinal pigment epithelium (RPE; n = 10) associated with the accumulation of melphalan in RPE leading to atrophic processes in the retina. Complications in the form of secondary glaucoma, severe fibrosis and retinal detachment, despite the complete resorption of the tumor, led not only to loss of vision, but also hindered visualization of the fundus and substantiated the need for enucleation in 3 cases. In other cases, enucleation was performed due to continued tumor growth (n = 16) or progression during treatment (n = 3).Conclusions. Retinoblastoma can be controlled with local chemotherapy. However, clinical and morphological examinations of enucleated eyes revealed and confirmed, along with tumor resorption, intraocular complications as a result of the toxic effect of the drugs and the presence of active tumor tissue to varying degrees of therapeutic pathomorphism, which can be explained by the resistance of RB to these drugs. Thus, a further search is needed for drugs that destroy the tumor and minimize the retinotoxic effect.

Serum and erythrocyte membrane fatty acid levels may be used as biomarkers to assess the severity of NAFLD

The aim of this work is to study the possibility of using blood serum (BS) fatty acids (FA) and erythrocytes (ER) as diagnostic markers of the severity of NAFLD. Materials and methods. We examined 52 patients with NAFLD (51.8 ± 3.9 years), confirmed by the NLFS index, and 20 apparently healthy men (49.2 ± 4.5 years). The degree of liver fibrosis was established by indirect elastometry (FibroScan® 502 Echosens, France). 27 patients had an initial degree of fibrosis (F0-1), 25 had severe fibrosis (F2-4). The study of the composition of fatty acids of Er and BS was carried out using a GC / MS system based on three Agilent 7000B quadrupoles (USA). Results. Significant differences in the levels of fatty acids in blood serum and erythrocyte membranes in patients with NAFLD were revealed, associated with the degree of fibrosis and necroinflammatory activity. To distinguish between mild and severe fibrosis in NAFLD, the levels of saturated fatty acids (myristic, pentadecane, margarine) and omega-3 PUFAs (eicosapentaenoic, docosapentaenoic, docosahexaenoic) were found to be significant (p = 0.002-0.0003). Saturated and monounsaturated FAs (palmitelaidic, palmitoleic, vaccenic) played a key role in differentiating the degree of necroinflammatory activity (minimal versus pronounced) (p = 0.03-0.005). The created diagnostic panels (FA of blood serum and erythrocyte membranes) made it possible to differentiate patients with NAFLD with varying degrees of fibrosis. Correlations of FA levels in erythrocyte membranes and blood serum with manifestations of metabolic syndrome, indicators of liver damage in patients with NAFLD were revealed. Conclusions. The established differences in fatty acid profiles of blood serum and erythrocyte membranes in patients with NAFLD, associated with the degree of fibrosis, necroinflammatory activity, manifestations of metabolic syndrome and indicators of liver damage, should be considered as promising biomarkers for assessing the severity of NAFLD.

A Generic Nomogram Predicting the Stage of Liver Fibrosis Based on Serum Biochemical Indicators Among Chronic Hepatitis B Patients

Introduction: Liver fibrosis staging is of great importance for reducing unnecessary injuries and prompting treatment in chronic viral hepatitis B patients. Liver biopsy is not suitable to act a screening method although it is a gold standard because of various shortcomings. This study aimed to establish a predictive nomogram as a convenient tool to effectively identify potential patients with different stages of liver fibrosis for patients with chronic hepatitis B.Methods: A nomogram for multinomial model was developed in a training set to calculate the probability for each stage of fibrosis and tested in a validation set. Fibrosis stages were subgrouped as followed: severe fibrosis/cirrhosis (F3–F4), moderate fibrosis (F2), and nil-mild fibrosis (F0–F1). The indicators were demographic characteristics and biochemical indicators of patients. Continuous indicators were divided into several groups according to the optimal candidate value generated by the decision tree.Results: This study recruited 964 HBV patients undergoing percutaneous liver biopsy. The multinomial model with 10 indicators was transformed into the final nomogram. The calibration plot showed a good agreement between nomogram-predicted and observed probability of different fibrosis stages. Areas under the receiver operating characteristics (AUROCs) for severe fibrosis/cirrhosis were 0.809 for training set and 0.879 for validation set. For moderate fibrosis, the AUROCs were 0.75 and 0.781. For nil-mild fibrosis, the AUROCs were 0.792 and 0.843. All the results above showed great predictive performance in predicting the stage of fibrosis by our nomogram.Conclusion: Our model demonstrated good discrimination and extensibility in internal and external validation. The proposed nomogram in this study resulted in great reliability and it can be widely used as a convenient and efficient way.

670Lifestyle risk factors for hepatocellular carcinoma in treated chronic hepatitis C patients

Background The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, associated with the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virological response (SVR). Methods This cross-sectional study was conducted between 2014 and 2017 using self-administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for post-SVR HCC. Results Of 202 participants, 18 had been diagnosed with post-SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95%CI, 1.08 to 83.90), and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95%CI, 1.37 to 12.46) were significantly associated with HCC. Among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with non-smokers, with marginal significance (OR, 5.61; 95%CI, 0.97 to 32.63). Conclusions In chronic hepatitis C patients with severe fibrosis, continued smoking could be a risk factor for post-SVR HCC. The relationship between gastric or duodenal ulcer history and post-SVR HCC should be investigated further. Key messages Smoking cessation may be preferred for chronic hepatitis C patients with severe fibrosis to prevent post-SVR HCC.

Native T1 Mapping and Magnetization Transfer Imaging in Grading Bowel Fibrosis in Crohn’s Disease: A Comparative Animal Study

In this study, we investigated the utility of native T1 mapping in differentiating between various grades of fibrosis and compared its diagnostic accuracy to magnetization transfer imaging (MTI) in a rat model of CD. Bowel specimens (64) from 46 CD model rats undergoing native T1 mapping and MTI were enrolled. The longitudinal relaxation time (T1 value) and normalized magnetization transfer ratio (MTR) were compared between none-to-mild and moderate-to-severe fibrotic bowel walls confirmed by pathological assessments. The results showed that the correlation between the T1 value and fibrosis (r = 0.438, p < 0.001) was lower than that between the normalized MTR and fibrosis (r = 0.623, p < 0.001). Overall, the T1 values (t = −3.066, p = 0.004) and normalized MTRs (z = 0.081, p < 0.001) in none-to-mild fibrotic bowel walls were lower than those in moderate-to-severe fibrotic bowel walls. The area under the curve (AUC) of the T1 value (AUC = 0.716, p = 0.004) was significantly lower than that of the normalized MTR (AUC = 0.881, p < 0.001) in differentiating moderate-to-severe fibrosis from none-to-mild fibrosis (z = −2.037, p = 0.042). Our results support the view that the T1 value could be a promising imaging biomarker in grading the fibrosis severity of CD. However, the diagnostic performance of native T1 mapping was not superior to MTI.

Hepatic steatosis as measured by the computed attenuation parameter predicts fibrosis in long-term methotrexate use

Introduction: To determine predictors of hepatic steatosis by the computed attenuation parameter (CAP) and fibrosis via transient elastography (TE) in persons on methotrexate (MTX) therapy with rheumatologic and dermatologic diseases. Methods: A single-centred retrospective cohort study was performed. Patients on >6 months of MTX for a rheumatologic or dermatologic disease who had undergone TE from January 2015 to September 2019 were included. Multivariate analysis was performed to determine predictors of steatosis and fibrosis. Results: A total of 172 patients on methotrexate were included. Psoriasis was the most frequent diagnosis ( n = 55), followed by rheumatoid arthritis ( n = 45) and psoriatic arthritis ( n = 34). Steatosis (CAP ≥245 dB/m) was present in 69.8% of patients. Multivariate regression analysis revealed that diabetes mellitus (OR 10.47, 95% CI 1.42–75.35), hypertension (OR 5.15, 95% CI 1.75–15.38), and BMI ≥30 kg/m2 (OR 16.47, 95% CI 5.56–45.56) were predictors of steatosis (CAP ≥245 dB/m). Predictors of moderate to severe fibrosis (Metavir ≥F2 = TE ≥8.0kPa) by multivariate regression analysis included moderate to severe steatosis (CAP ≥270 dB/m) (OR 8.36, 95% CI 1.88–37.14), diabetes mellitus (OR 2.85, 95% CI 1.09–7.48), hypertension (OR 5.4, 95% CI 2.23–13.00), dyslipidemia (OR 3.71, 95% CI 1.50–9.18), and moderate alcohol use (OR 3.06, 95% CI 1.2–7.49). Conclusions: In patients on MTX for rheumatologic and dermatologic diseases, hepatic steatosis as measured by CAP was common and moderate to severe steatosis predicted moderate to severe fibrosis.

Association of TM6SF2 rs58542926 with Hepatic and Extrahepatic Alterations in Chronic Hepatitis C Patients

Human genetic variants play major roles in predicting and prognosis of several diseases. The effect of rs58542926 variant in transmembrane 6 superfamily member 2 (TM6SF2) gene on liver fibrosis among patients with chronic hepatitis C (CHC) is still debatable. The aim of this study is to investigate the possible effects of this variant in CHC patients. The study comprised 351 subjects: 250 CHC patients with different fibrosis stages (F0-F4) and 101 healthy volunteers. TM6SF2 (rs58542926) genotype was determined for all subjects. Blood samples were collected for complete blood count and biochemical analysis and cohort subjects were genotyped for the variant TM6SF2 rs58542926. Fibrosis staging was performed using Fibrotest and Fibroscan standard tests. The presence of the minor allele was significantly associated with severe liver fibrosis, as well as thrombocytopenia as an extrahepatic alteration. In addition, there was a significant association between the minor allele and lower thrombopoietin levels. The association of TM6SF2 genotype with thrombocytopenia was explored by measuring plasma thrombopoietin (TPO) levels for CHC patients. The results showed an association with extrahepatic alteration (thrombocytopenia) through its effect on plasma TPO level, and consequently on platelets production, which raises questions about the role of this variant in HCV treatment outcome. In conclusion, the occurrence of the minor allele of the variant rs58542926 can be linked to severe fibrosis stages as well as thrombocytopenia, enabling this variant to be used as a diagnostic pharmacogenetic marker for predicting the risk of fibrosis onset in CHC patients.