Viral Cirrhosis Research Articles

Factors associated with nonadherence to surveillance for hepatocellular carcinoma among patients with hepatic C virus cirrhosis, 2000-2015.

Hepatocellular carcinoma (HCC) surveillance can detect the early stage of tumors and lead to improved survival. Adherence to guideline-concordant HCC surveillance is crucial in at-risk populations, including patients with hepatic C virus (HCV) cirrhosis. This study was conducted to identify patient and provider factors associated with nonadherence to HCC surveillance in patients with HCV cirrhosis. Data were primarily obtained from the Taiwan National Health Insurance Research Database for the 2000 to 2015 period. Adult patients newly diagnosed as having HCV cirrhosis between 2003 and 2012 were enrolled. Each patient was followed up for 3 years and until the end of 2015. Annual HCC surveillance was defined as the uptake of an abdominal ultrasound and alpha-fetoprotein (AFP) test annually during the 3-years follow-up. Nonannual surveillance was defined as the lack of an annual abdominal ultrasound and AFP test during the same 3-years period. Multinomial logistic regression models were applied to determine factors influencing adherence or nonadherence to annual HCC surveillance. We included a total of 4641 patients with HCV cirrhosis for analysis. Of these patients, only 14% adhered to annual HCC surveillance. HCC surveillance improved in later years, compared with the earlier phases of the study period. Patients with HCV cirrhosis comorbid with coronary artery disease (CAD) or chronic obstructive pulmonary disease (COPD) or those with a relatively high number of comorbidities had a significantly higher likelihood of nonadherence. Patients who primarily received care from internists were significantly less likely to exhibit nonadherence to annual HCC surveillance compared with patients receiving care from physicians of other specialties. Patients who primarily received care from physicians practicing in larger hospitals were significantly less likely to exhibit nonadherence. HCC surveillance rates remain unacceptably low among high-risk patients, and our findings may be helpful in the development of effective interventions to increase HCC surveillance. The effective incorporation of HCC surveillance into routine visits for other chronic comorbidities, particularly for CAD or COPD, may be crucial for increasing HCC surveillance.

Non-invasive model for predicting esophageal varices based on liver and spleen volume.

Upper endoscopy is the gold standard for predicting esophageal varices in China. Guidelines and consensus suggest that patients with liver cirrhosis should undergo periodic upper endoscopy, most patients undergo their first upper endoscopy when esophageal variceal bleeds. Therefore, it is important to develop a non-invasive model to early diagnose esophageal varices. To develop a non-invasive predictive model for esophageal varices based on liver and spleen volume in viral cirrhosis patients. We conducted a cross-sectional study based on viral cirrhosis crowd in the Second Affiliated Hospital of Xi'an Jiaotong University. By collecting the basic information and clinical data of the participants, we derived the independent risk factors and established the prediction model of esophageal varices. The established model was compared with other models. Area under the receiver operating characteristic curve, calibration plot and decision curve analysis were used to test the discriminating ability, calibration ability and clinical practicability in both the internal and external validation. The portal vein diameter, the liver and spleen volume, and volume change rate were the independent risk factors of esophageal varices. We successfully used the factors to establish the predictive model [area under the curve (AUC) 0.87, 95%CI: 0.80-0.95], which showed better predictive value than other models. The model showed good discriminating ability, calibration ability and the clinical practicability in both modelling group and external validation group. The developed non-invasive predictive model can be used as an effective tool for predicting esophageal varices in viral cirrhosis patients.

Possibilities of cryosurgery in the treatment of the abdominal cavity diseases

Aim. To study the immediate results of the use of cryosurgical instruments and ultra-low temperature liquid nitrogen in diseases of abdominal organs.Materials and research methods. The article presents the results of surgical treatment using ultra-low temperature liquid nitrogen (196oC) for 308 patients with diseases of the abdominal organs in the Department of Liver and Pancreas Surgery of the Institute of Gastroenterology of the Republic of Tajikistan from 2016 to 2022.The results and discussion. The authors proposed an algorithm for the use of the ultra-low temperature of liquid nitrogen in the treatment of diseases of the abdominal organs after the development of the latest cryogenic equipment. It turned out that the resulting cryodestruction leads to the death of parasitic elements of alveococcosis, echinococcosis, and liver tuberculosis, as well as to cytolysis of atypical calls in hepatocellular carcinoma. The most important advantage of liver cryosurgery, especially in concomitant chronic viral hepatitis and liver cirrhosis, is a reliable parenchymal haemo-and cholestasis, a decrease in intraoperative blood loss, an increase in the radicality of an operation, and reliable prevention of intraoperative dissemination of malignant and parasitic diseasesConclusion. The accumulated experience of surgeries for various diseases of the abdominal organs using ultra-low temperature liquid nitrogen allows concluding that cryosurgery of the abdominal organs has an undoubted prospect. The positive characteristic of using cryotechnology in the treatment of severe diseases of abdominal organs suggests that it is advisable to introduce the method into clinical practice on a wide scale.

Comparison of Electrocardiogram and QT Interval between Viral Hepatitis Cirrhosis and Alcoholic Cirrhosis.

Objective This study aims to compare the electrocardiogram (ECG) abnormalities and QT interval prolongation in 2,886 patients with viral hepatitis cirrhosis and 643 patients with alcoholic cirrhosis in order to understand the characteristics of ECG in patients with cirrhosis and provide information and evidence for clinical diagnosis and treatment. Methods The ECG data of patients with viral hepatitis cirrhosis and alcoholic liver cirrhosis in the outpatients and inpatients of our hospital from August 2012 to July 2018 were reviewed. The ECG data were recorded, and the ECG report was issued by ECG experts to analyze the abnormal ECG and QT interval of patients in these two groups. Results In the present study, 1,132 (39.22%) of the 2,886 patients with viral liver cirrhosis and 322 (50.08%) of the 643 patients with alcoholic liver cirrhosis had an abnormal ECG (P < 0.001). Among patients with QT prolongation, 388 patients had viral liver cirrhosis (13.44%) and 170 patients had alcoholic liver cirrhosis (26.44%, P < 0.001). Conclusion The hemodynamics and electrophysiology of the myocardium are often changed in patients with cirrhosis, and ECG changes may also occur. QT interval prolongation is one of the most common electrophysiological abnormalities in patients with cirrhosis, and QT prolongation is more common in patients with alcoholic liver cirrhosis. Prolonged QT is associated with severe arrhythmia and sudden death and can warn of malignant arrhythmia and sudden death. Therefore, the routine detection of abnormal ECG and QT interval in patients with liver cirrhosis is of significant importance for preventing malignant events.

S1338 The Prevalence of Protein-Calorie Malnutrition Among Patients With Alcoholic, Non-Alcoholic and Chronic Viral Cirrhosis in the United States: A Population-Based Study

S1338 The Prevalence of Protein-Calorie Malnutrition Among Patients With Alcoholic, Non-Alcoholic and Chronic Viral Cirrhosis in the United States: A Population-Based Study

Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction= .029) and those without elevated triglycerides levels (P for interaction= .047). In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.

Assessing the Risk of Further Decompensation and Survival in Patients With Cirrhosis With Variceal Bleeding as Their First Decompensation Event.

Limited data exist on long-term outcomes of patients with compensated cirrhosis presenting with acute variceal bleeding (AVB) as an index and lone decompensating event. This study aimed to evaluate the incidence of further decompensation, survival, and risk factors of mortality in these patients. Patients with otherwise compensated cirrhosis presenting with AVB as their index decompensating event (n = 463) were analyzed in this single-center retrospective study. The incidence of individual decompensation events and survival was estimated using competing risk analysis. Risk factors for poor outcomes were identified. The mean age was 47.4 (13.2) years, with most patients (86.5%) being males. Alcohol-related liver disease (42.3%) and viral cirrhosis (22.4%) were the main etiologies with a median Model for End-Stage Liver Disease score of 14 (11-15) at baseline. Over a median follow-up of 42 (24-62) months, 292 patients experienced further decompensations: ascites (n = 283; 96.9%), rebleeding (n = 157; 53.8%), and hepatic encephalopathy (n = 71; 24.3%). Most events occurred with similar frequency across different etiologies, except acute-on-chronic liver failure, which was more common in nonviral cirrhosis (Gray test, P = 0.042). Patients with viral and nonviral cirrhosis had similar survival (5-year survival: 91% and 80.1%, respectively; P = 0.062). Patients with early further decompensations (onset <6 weeks of index AVB event) (n = 40) had a higher mortality (52.5% vs 20.2% for late decompensations; P < 0.001). Active alcohol consumption (hazard ratio [HR]: 9 [5.31-15.3], P < 0.001), high white blood cell count at presentation (HR: 2.5 [1.4-4.4], P = 0.001), and early decompensation (HR: 6.2 [3.6-10.6], P < 0.001) predicted poor survival. Despite a high incidence of further decompensation, 5-year survival of patients at this stage of cirrhosis is more than 80% across all etiologies in the absence of early further decompensation and active alcohol consumption.

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-β1 in Wistar Rats.

Background Shi-Wei-Gan-Ning-San (SWGNS) is a classic Tibetan prescription, which has obvious clinical effects in the treatment of viral hepatitis, fatty liver, liver fibrosis, liver cirrhosis, liver cancer, and other liver injuries. However, animal studies and mechanism studies are still lacking. This study aimed to investigate its hepatoprotective efficacy and pharmacological mechanism in animal experiments. Methods Chronic liver injury was induced by oral administration of carbon tetrachloride (CCl4) in Wistar rats for 13 weeks. SWGNS was administered orally to rats at doses of 235, 705, and 1410 mg/kg for 13 weeks. Blood samples were collected for biochemical, ELISA, and radioimmunoassay. Livers were harvested for H&E and immunohistochemical staining. The major constituents of SWGNS were analyzed by HPLC. In vitro experiments were used to explore the protective effect of Crocin on BRL-3A in the environment of H2O2. Results SWGNS reversed weight loss is induced by CCl4. Serum assays showed that SWGNS reduced CCl4-induced alanine aminotransferase, aspartate aminotransferase, total bilirubin, and γ-glutamyltransferase levels and increased the total protein and albumin levels. Histopathological evaluation showed that SWGNS alleviated hepatic steatosis, fibrosis, and inflammation. Furthermore, SWNGS reduced CCl4-induced elevations of TGF-β1, hyaluronic acid, laminin, and collagen IV in serum and reduced the high expression of α-SMA in tissues. Moreover, Crocin I and II are the main components of SWGNS. Crocin attenuated the damaging effects of H2O2 on BRL-3A. Conclusions In conclusion, SWGNS alleviated CCl4-induced chronic liver injury by inhibiting the TGF-β1 pathway. This plays an important role in promoting traditional Tibetan medicine in clinical practice.

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria). All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV low risk (i.e., low probability of high-risk varices [HRV]) if platelets were >120 × 10 9 /L and serum albumin >3.6 g/dL or RESIST-HCV high risk (i.e., high probability of HRV) if platelets were <120 × 10 9 /L or serum albumin <3.6 g/dL. The primary outcome was the progression to HRV. The area under the receiver operating characteristic curve and decision curve analysis of noninvasive criteria were calculated. The cohort consisted of 353 patients in Child-Pugh class A (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95% CI 6.7%-13.5%) developed HRV. At the last EGDS, 178 patients (50.4%) were RESIST-low risk, and 175 (49.6%) were RESIST-high risk. RESIST-HCV criteria showed the highest area under the receiver operating characteristic curve (0.70, 95% confidence interval 0.65-0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false-positive rate (45.7%), compared with elastography-based criteria. Decision curve analysis showed that RESIST-HCV had higher clinical utility than elastography-based criteria. Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.

Analysis and significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term NAs antiviral therapy in patients with hepatitis B virus cirrhosis

Objective: To analyze the significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term nucleos(t)ide analogues (NAs) antiviral therapy in patients with hepatitis B virus cirrhosis. Methods: 97 cases with hepatitis B virus cirrhosis treated with NAs antiviral therapy for at least 3 years between May 2018 to July 2019 were selected. High-sensitivity HBV DNA (<20 IU/ml), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), HBsAg, HBeAg and HBV RNA at least twice every 6 months were detected. According to Child-Pugh classification, HBeAg, HBsAg level, and HBV RNA level intergroup comparison was performed. Rank sum test, χ2 test and linear regression analysis were performed on the data. Results: Compared with the HBV RNA level of child-Pugh class A patients, the HBV RNA level of Child-Pugh class B+C patients were significantly higher [4.1 (0,4.9) log10 copies/ml and 2.0 (0,3.5) log10 copies/ml], and the difference was statistically significant (Z=2.370, P<0.05). According to different HBeAg levels, they were divided into HBeAg positive and negative group, and the quantitative comparison of HBV RNA levels between the two groups were 2.0 (0, 4.5) log10 copies/ml and 1.0 (1.0, 2.0) log10 copies/ml, respectively, and the difference was statistically significant (Z=3.233, P<0.05). According to different HBsAg levels, they were divided into three groups: HBsAg≤100 IU/ml, 100<HBsAg<1 000 IU/ml, and HBsAg≥1 000 IU/ml, and the quantitative comparison of HBV RNA levels among the three groups were 0 (0, 2.0) log10, 2.0 (0,4.6) log10, and 2.2 (2.0, 4.7) log10 copies/ml, respectively, and the difference was statistically significant (H=11.265, P<0.05). Gender, age, ALT, AST, GGT, HBsAg, and HBeAg were included for linear regression analysis, and the HBsAg and AST levels were correlated with HBV RNA quantification (P<0.05). Adverse events occurrence during 1-year follow-up were recorded. 19 (31.7%) out of 60 cases had adverse events with detectable HBV RNA, and 3 (8.1%) out of 37 cases had adverse events with undetectable HBV RNA, and the difference was statistically significant (χ2=7.24, P<0.05). Conclusion: HBV RNA can still be detected after HBV DNA falls below the detection limit in patients with hepatitis B virus cirrhosis treated with long-term NAs antiviral therapy. HBV RNA quantification level is higher in patients with Child Pugh class B and C. Patients with detectable HBV RNA has higher proportion of adverse events, and AST and HBsAg levels may be correlated with serum HBV RNA.

The risk of variceal bleeding during endoscopic retrograde cholangiopancreatography.

Endoscopic retrograde cholangiopancreatography (ERCP) is a widely performed procedure. However, the risk of variceal bleeding during ERCP has rarely been assessed. This study aims to evaluate the risk of variceal bleeding in patients with esophageal varices (EV) undergoing ERCP. From October 2010 to November 2017, the study retrospectively enrolled 75 cirrhotic patients who received elective ERCP. The patient's risk of gastrointestinal (GI) and variceal bleeding and other procedure-related adverse events within 30 days of ERCP were evaluated. Among the 75 patients, 45 patients (60.0%) had EV. Most of the patients were males (65.3%), and there were high rates of viral hepatitis B-related cirrhosis (36.0%), Child-Pugh B (49.3%), and an indication of choledocholithiasis (40.0%). Thirty-three of 45 (73.3%) patients had high-risk EV, and nine (20.0%) patients had concomitant gastric varices. There was no esophageal variceal bleeding; however, one patient had gastric variceal bleeding after ERCP. Nonvariceal significant GI bleeding occurred in three patients with EV and one without EV ( p = 0.529). Post-ERCP pancreatitis occurred in three patients with EV and five without EV ( p = 0.169). No perforation or procedure-associated mortality was noted. The risk of esophageal variceal bleeding within 30 days of ERCP is neglectable, except for a patient who suffered from gastric variceal bleeding. Other complications, such as nonvariceal bleeding and pancreatitis, are also no higher in patients with EV. Therefore, ERCP is generally a safe procedure for a patient with high-risk esophageal varices.

Endoscopic Prophylaxis and Treatment of Portal-Genesis Oesophageal Haemorrhage

Background. Portal hypertension-triggered oesophageal and gastric variceal bleeding is the most dangerous and threatening complication, with an up to 50–70 % mortality at first episode. High-mortality repeated bleeding develops subsequently in 30–50 % patients, with the proved 100 % recurrence rate in the first two years following the first episode. The world experience dictates further research to continue towards developing new surgical methods and approaches.Aim: to evaluate the treatment efficacy of pneumatic endoscopic band ligation of bleeding oesophageal varices (OV).Materials and methods. The experience of applying pneumatic endoscopic ligation treatment in the patients managed at the General Surgery Unit of the Clinical Hospital of the Kyrgyz Republic Presidential Administration during 2017–2019 was analysed. Endoscopic ligation is a modern minimally invasive and less traumatic intervention used to markedly reduce mortality and improve quality of life in patients with portal hypertension syndrome. The evidence on 76 patients following endoscopic OV ligation was summarised. The patient age ranged from 11 to 70 years (mean 46.26 years); 40 men (52.6 %) and 36 women (47.4 %) were included. Among the 76 patients, portal hypertension was caused by viral cirrhosis in 38, hepatitis B in 5, delta agent hepatitis B in 18, hepatitis C in 13, a hepatitis B–C combination in 1 and a delta agent hepatitis B — hepatitis C combination in 1 patient. In 21 patients, cirrhosis was of unknown aetiology. A portal vein malformation was observed in 13 people of whom 4 had it combined with thrombosis.Results. A total of 94 ligation procedures were performed in 76 patients with grade II–III OV. Some patients needed to undergo the procedure several times, 18 patients had 2 sessions. Two cases required 3 and 4 sessions each. Moderate oesophageal soreness was reported in 32 patients for 1–6 days following the ligation. No complications were registered during the operation. In early postoperative period, 2 patients developed recurrent bleeding, with haemostasis re-achieved by a repeated vein ligation below bleeding.Conclusion. Hence, small invasiveness and minor traumatism coupled with high efficiency and lesser complications render endoscopic ligation the method of choice in primary and secondary prophylaxis and treatment of OV. Endoscopic ligation improves the patient’s quality of life, allows an extra time for conservative treatment and longer period to liver transplantation.

Abstract 5721: c-Myc expression coupled with loss of cytoplasmic Miz-1 expression and its re-localization to a nuclear expression in high grade cholangio and hepatocholangio carcinomas

Abstract Miz-1 (Myc-interacting zinc finger) activates target genes through transcription factors that are regulated by specific antimitogenic signals. Association with Myc converts Miz-1 from being a transcriptional activator to a repressor. This binding and the formation of Myc/Miz-1 complex induces a change in the biophysical properties of the Miz-1 protein, rendering the complex insoluble and causing to relocalize inside the nucleus. In addition, this association stabilizes Myc and as a result represses transcription. With uncontrolled tumor progress, metastatic tumor expansion can occur through epithelial-to-mesenchymal transition (EMT) and the induction of ZEB-1 (Zinc Finger E-Box Binding Homeobox-1). Zeb-1 expression is highly associated with aggressive behavior tumor types. A cohort of 98 human cholangiocarcinoma carcinoma (CC) including 14 with mixed (CC)/(HCC) resected cases whose formalin fixed paraffin embedded (FFPE) tissue sections containing adjacent benign and malignant tumor lesions were examined by immunohistochemistry (IHC) using Miz-1 (ZBTB17), ZEB-1 (OT13G6), c-Myc (Y69), and Ki-67 (Mib-1) monoclonal antibodies. The clinicopathologic variables, including viral hepatitis, cirrhosis, tumor size, grade and number, vascular invasion, tumor-node-metastasis (TNM) stage, were obtained from each patient’s medical records. The variables were assessed for correlation with the immunohistochemical results. Compared to the adjacent benign liver section, reduction of Miz-1 expression was observed in 98/98 (100%) (P&amp;lt;0.0001) cases, while positive expression of c-Myc, Ki-67 (&amp;gt; 5%), and ZEB-1 was observed in 18/98 (18.36%) (P&amp;lt;0.0001), 27/98 (27.55%) (P=0.000003), and 15/98 (15.30%) (P&amp;lt;0.00001) cases respectively. Of note, complete loss of Miz-1 expression was noted in 20/36 (55.55%) (P=0.106) high grade tumors (III/IV) associated with positive c-Myc, Ki-67 (&amp;gt;5%), ZEB-1, and nuclear Miz-1 expression in 12/20 (60%) (P=0.12) cases (4 CC and 8 mixed (CC)/(HCC) cases). All 12 cases with positive ZEB-1 had confirmed positive lymph node involvement. These results support the role of Miz-1 as one of the intermediary checkpoints required for the induction of cell cycle arrest and apoptosis. Positive c-Myc/ZEB-1 coupled with Miz-1 reduced cytoplasmic and its re-localization to a nuclear expression confirms the transcriptional repressor role of the Myc/Miz-1 complex and the activation of the ZEB-1 gene as a predictor of increased metastatic expansion, therapy resistance, and poor survival in high grade CC, and CC/HCC cases. These findings correlate with a cohort of an adequate number of differently graded lesions from 147 HCC cases that showed similar expression pattern of Miz-1, c-Myc and Zeb-1 to better confirm our hypothesis in epithelial derived human malignancies with frequently amplified 8q24 chromosome. Citation Format: Joeffrey J. Chahine, Sumeyye Culfaci, DongHyang Kwon, Pamela Tuma, Bhaskar V.S. Kallakury. c-Myc expression coupled with loss of cytoplasmic Miz-1 expression and its re-localization to a nuclear expression in high grade cholangio and hepatocholangio carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5721.

Analysis of Quantitative Data of Arterial Spin Labeling Perfusion of the Liver at Admission and Follow up of Patients with Viral Cirrhosis

The aim of this work is to analyze quantitative data of magnetic resonance ASL-perfusion of the liver at admission and follow up of patients with viral cirrhosis.The study included 34 patients with viral liver cirrhosis: 23 (67.6 %) men and 11 (32.4 %) women. All subjects underwent abdominal ultrasound with Dopplerography of the abdominal vessels, shear wave elastography, Arterial spin Labeling (ASL) — Perfusion of the liver by magnetic resonance imaging. Post-processing of ASL-perfusion images was carried out, their quantitative assessment in regenerative liver nodules and the parenchyma structure was carried out. It was found that for patients with liver cirrhosis according to Child-Pugh Class A, regardless of the degree of activity, the values of ASL-perfusion of the liver were 99.6 ± 1.8 ml/100g/min, with class B — 95.6 ± 4.9 ml/100g/min, with class C — 98.5 ± 2.6 ml/100g/min. To determine the diagnostic significance of liver ASL-perfusion, a generalized prognosis ratio ΔM = MNBF/ MHBF was calculated, where MNBF is a quantitative indicator of volumetric blood flow in the regenerative nodule, MHBF is a quantitative indicator of volumetric hepatic blood flow in the surrounding parenchyma. The results obtained by ASL-perfusion were compared with the data of shear wave elastography.For patients with viral liver cirrhosis the quantitative indicator of ASL-perfusion of the liver is less than 101.4 ml/100g/min. To predict the course of viral etiology cirrhosis, the prognosis ratio ΔM should be taken, and if ΔM &gt; 1, this indicates a poor prognosis (fibrosis progression), if ΔM ≤ 1 — a favorable one (no fibrosis progression). Diagnostic and prognostic significance of ASL-liver perfusion for patients with viral cirrhosis at admission to the hospital — AUROC = 0.865 (95 % CI 0.843–0.928) and follow up — AUROC = 0.915 (95 % CI 0.881–0.946).

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease.

This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease. This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6-12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality. The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46-55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48-5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55-0.56). HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.

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

BackgroundWe 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).MethodsWe 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.ResultsOne 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.ConclusionsOur 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.

Non-hepatocellular carcinoma management: A SEER database analysis.

e16108 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, however, chronic viral hepatitis and cirrhosis place patients at an increased risk for non-HCC malignancies as well. A major treatment option for these tumors is local tumor destruction via a number of minimally invasive techniques available to interventional radiologists. This study assessed the prognostic impact of various liver-directed local tumor therapies in the management of non-HCC liver cancer. Methods: We searched the SEER-18 database for malignant liver cancers not coded as HCC (8170-8175) that were diagnosed between 2000-2018. Patients were excluded if the cause of death was not associated with their cancer according to SEER’s cancer-specific death categorization. The SEER database tracks survival up to 60 months. SPSS was used for all descriptive and univariate survival statistics. Results: A total of 228 patients were collected from this search. 59.6% of cases were from males and the average age was 64 years old (median = 65). 60.1% were in non-Hispanic White patients, followed by Hispanic (16.2%), non-Hispanic Asian or Pacific Islander (14.0%), and non-Hispanic Black (9.2%) patients. Of the 170 patients with staging coded, 62.9% were local, 24.7% were regional, and 12.4% were distant. 36.8% of patients received some form of chemotherapy, while only 3.1% received radiation. When grouped by age range (&lt; 49, 50-69, 70+), survival did not differ between groups. Sex also did not influence survival (p = .325). Patients that received chemotherapy had worse outcomes, likely due to worse staging which was negatively associated with survival (p &lt; .05). Radiation did not significantly improve survival. Of the local tumor destruction therapies, Heat-Radio-Frequency ablation (RFA) (n = 150) improved survival significantly in comparison to: local tumor destruction not otherwise specified (n = 42), photodynamic therapy (n = 1), electrocautery (n = 4), cryosurgery (n = 4), and ultrasound or acetic acid (n = 15) (all p &lt; 0.05). Laser surgery (n = 3) and intratumoral injection of alcohol (n = 9) had no significant outcome differences. RFA had an estimated mean survival time of 35.7 months while all other interventional radiology modalities combined had a mean estimated survival time of 21.4 months (p &lt; .000). Conclusions: Though limitations of a small sample size and univariate statistical analyses were present in this study, RFA likely has improved survival compared to other interventional radiology modalities used in the treatment of non-HCC liver cancer.

Sarcopenic obesity in liver disease: Handling both sides of the penny

AbstractSkeletal muscle and fat tissue show distinct pathophysiological roles and pivotal functions. The culmination of muscle wasting and fat accumulation represents an opposite terminal of each state. Specifically, this situation has been designated as sarcopenic obesity. However, sarcopenic obesity still lacks a unanimous definition, diagnostic criteria, and generalized modalities for assessment in the context of versatile liver diseases. Moreover, the underpinning mechanisms by which a combination of abnormal skeletal muscle and fat tissue leads to the progression of liver disease and impairs health‐related consequences are still elusive. Additionally, the interplay between skeletal muscle and fat, and the driving factors that shift different body compositions are not well understood. Therefore, in this review, we discuss skeletal muscle and fat components, with the purpose of conceptualization, as well as interpret their roles in liver diseases. We focus on the definitions, diagnostic criteria, and currently available measurements for sarcopenic obesity in the literature. We comprehensively discuss recent data and evidence regarding the potential role of sarcopenic obesity in the development and progression of numerous liver diseases and associated conditions, including nonalcoholic fatty liver disease, chronic viral hepatitis, cirrhosis, and liver transplantation. Furthermore, explicit information related to the pathogenesis of sarcopenic obesity from basic research is also provided in this narrative review. Finally, we discuss, from the clinical perspective of view, how to manage sarcopenic obesity using nutritional, physical, and pharmacological methods.

Analysis of the Chromosomal Aberrations in Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Hepatocellular Carcinoma Patients (HCC) in Mosul City, Iraq

Abstract. Hepatocellular carcinoma (HCC) (also known as liver cancer) is one of the most frequent cancers in humans. HCC is linked to chronic hepatitis B and C virus infection, cirrhosis, and excessive alcohol consumption. The aim of this study was to use Metaphase chromosome analysis in whole blood to determine chromosomal aberrations (CA) in HBV, HCV, and HCC patients. A cohort of 145 samples have been collected from participants from the date of 5 \ 1 \ 2020 to 15\9\ 2021. Among those samples are (40 healthy controls, HBV 38, 44 HCV, and HCC 23) to make cytogenetic evaluation by observing the analysis of chromosome aberration. Our study showed that the chromosome aberration With Gap was higher in the HCC patient group followed by HBV patient group. also, the results showed that of the chromosome aberration without Gap in the HCC, and HCV patient groups were significantly higher in females than in males. the results showed that higher break, DIC was in HBV patients group followed by HCV patients group. the results showed that deletion, and ace were higher in the HCV and HCC patient group followed by HBV patient group. Finally with RO. Trans., the results showed that ace was higher in the HCV, and HBV patient groups. In conclusion, we indicate that HBV, HCV, and HCC patients have chromosomal instability because of their chromosome aberration levels.

Genomic Relevance of FGFR2 on the Prognosis of HCV-Induced Hepatocellular Carcinoma Patients.

The Fibroblast Growth Factor Receptors (FGFRs) are known to regulate cancer metabolism in different tumor types, including hepatocellular carcinoma (HCC). Several risk factors are associated with HCC, of which viral infections (Hepatitis B and C) and cirrhosis are prominent. In Pakistan as well as in highly developed countries like the United States, hepatitis C virus HCV infections are most commonly reported in HCC. Here, we aimed to investigate the clinical relevance of FGFR receptors in HCC and their role in HCV-positive HCC cases. 264 HCC samples along with their clinical information and 96 normal liver samples were collected. qPCR was done to estimate the expression of FGFR1, FGFR2, FGFR3 and FGFR4. Three independent HCV-induced HCC cohorts (containing 293 HCC samples) were used for validation. According to in vitro results, FGFR1 was upregulated in HCV+ HCC patients. However, in all three independent cohorts of HCC, significant a down-regulation of FGFR1 was observed. FGFR2 overexpression was observed in the in vitro cohort as well as in three independent HCC cohorts. Interestingly, a strong correlation of FGFR2 expression was observed between cirrhosis and HCV in all four HCC cohorts. Our study suggested that FGFR2 expression can be used to classify HCC patients based on HCV infection. This FGFR2-based classification may lead to new therapeutic strategies against HCV-positive HCC subtypes.