Presence Of Hepatocellular Carcinoma Research Articles

Myosteatosis Is Associated With Frailty and Poor Physical Function in Patients Undergoing Liver Transplant Evaluation: A Cohort Study.

Myosteatosis is fat infiltration within skeletal muscle. The impact of myosteatosis on physical function and clinical outcomes in patients referred for liver transplantation (LT) is unclear. We explored associations between myosteatosis and sarcopenia, frailty, physical function, and pre- and early post-LT outcomes. Myosteatosis was assessed by computed tomography (CT) in 237 patients referred for LT (March 2018 to September 2022). Chi-square/Fishers exact tests and multivariable regression compared myosteatosis and sarcopenia, frailty (liver frailty index), physical function (short physical performance battery, SPPB); and associations with pre-LT unplanned hospitalizations, post-LT surgical complications (Clavien-Dindo grade≥3), and LT admission length of stay (LOS). Kaplan-Meier and Cox-proportional hazards models explored myosteatosis and time to LT and unplanned admission. Fine-Gray model evaluated the competing risks of receiving an LT. Myosteatosis was present in 74 (31%) patients. Patients with myosteatosis were 2.5 times (95% confidence interval [CI] 1.1-5.7, p=0.03) more likely to be frail, and 3.0 times (95% CI 1.6-5.6, p<0.001) more likely to have a poor physical function (SPPB≤9/12) than those without myosteatosis. Patients with myosteatosis versus those without were more likely to have a pre-LT unplanned hospitalization (51% vs. 36%, p=0.03), but significance was lost after adjusting for age, sex, Model for End-stage Liver Disease (MELD), and the presence of hepatocellular carcinoma. Myosteatosis did not impact the likelihood of receiving an LT (p=0.39), post-LT complications (p=0.93), or LOS in intensive care unit (ICU) (p=0.66) or hospital (p=0.34). Myosteatosis is prevalent in patients referred for LT and is associated with impaired physical function. Using existing CTs to assess myosteatosis in practice may help identify physically compromised patients.

Vliv polymorfizmů PNPLA3 rs738409 a TM6SF2 rs58542926 dárce a příjemce na dlouhodobé přežívání pacientů po transplantaci jater

Summary Introduction: The variants rs738409 c.444C&gt;G (p.I148M) in patatin-like phospholipase domain-containing 3 (PNPLA3) and rs58542926 c.499G&gt;A (p.E167K) in TM6SF2 (transmembrane 6 superfamily member 2) are significant genetic risk factors of development and progression of non-alcoholic fatty liver disease (NAFLD). In both variants, increased liver-specific mortality was described, while the impact on all-cause mortality was not proved. The aim of the study was to evaluate the impact of PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively on long-term patient survival after LT. Methods: We evaluated long-term patient survival in a cohort of 268 adult LT recipients, in whom PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively were available and steatosis was evaluated in liver graft biopsy 6–30 months after LT. The median fol low-up was 17 years. The Kaplan-Meier model was used for the survival estimates and the Cox proportional hazard model was used to assess the predictive value of the chosen variables. Results: Increased recipient age (P &lt; 0.001), male sex (P = 0.014), alcoholic (P = 0.021) or HCV (P = 0.042) etiology of liver cirrhosis, and presence of hepatocellular carcinoma (P = 0.009) negatively influenced long-term patient survival after LT. PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the recipient and donor respectively had no effect on patient survival. Conclusion: Although PNPLA3 c.444G and TM6SF2 c.499A variants of the donor increase the risk of steatosis of the liver graft after LT, we did not prove a negative impact of these genotypes of the donor and recipient on long-term patient survival after LT. Keywords PNPLA3, TM6SF2, steatosis, MASLD, NAFLD, liver transplantation, patient survival

Safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy associated with spontaneous portosystemic shunts

This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 μmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Value of magnetic resonance imaging for diagnosis of LR‑3 and LR-4 lesions coexisting with hepatocellular carcinoma.

To explore which preoperative clinical data and conventional magnetic resonance imaging (MRI) features may indicate the presence of hepatocellular carcinoma (HCC) in HCC patients coexisting with LR-3 and LR-4 lesions. HCC Patients coexisting with LR-3 and LR-4 lesions who participated in a prospective clinical trial (XX) were included in this study. Two radiologists independently assessed the preoperative MRI features and each lesion was assigned according to the liver imaging reporting and data system (LI-RADS). The preoperative clinical data were also evaluated. The relative values of these parameters were assessed as potential predictors of HCC for coexisting LR-3 and LR-4 lesions. We enrolled 102 HCC patients (58.1 ± 11.5years; 84.3% males) coexisting with 110 LR-3 and LR-4 lesions (HCCs group [n = 66]; non-HCCs group [n = 44]). The presence of restricted diffusion (OR: 18.590, p < 0.001), delayed enhancement (OR: 0.113, p < 0.001), and mild-moderate T2 hyperintensity (OR: 3.084, p = 0.048) were found to be independent predictors of HCC diagnosis. The sensitivity and specificity of the above independent variables for the diagnosis of HCC ranged from 66.7 to 80.3% and 56.8 to 88.6%, respectively. ROC analysis showed that, in discriminating HCC, the AUCs of the above factors were 0.777, 0.686, and 0.670, respectively. Combining these three findings for the prediction of HCC resulted in a specificity greater than 97%, and the AUC further increased to 0.874. The presence of restricted diffusion, delayed enhancement, and mild-moderate T2 hyperintensity can be useful features for risk stratification of coexisting LR-3 and LR-4 lesions in HCC patients. Trial registration a prospective clinical trial (ChiCTR2000036201).

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan

BackgroundBoth European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens’ safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists.Methods7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data.ResultsOverall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2–4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3–4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2–4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2–4 abnormalities (p < 0.01).ConclusionsReal-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study’s results, can further identify patients who can be safely managed by non-specialist care.Graphical

Hypoalbuminemia and Risk of Portal Vein Thrombosis in Cirrhosis

Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n= 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P= .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Impact of Portal Vein Thrombosis on the Outcomes of Liver Transplantation

Portal vein thrombosis (PVT) occurs in up to 17.9% of patients awaiting liver transplantation. It may impact post-liver transplantation survival negatively. The liver transplant procedures performed in our transplant center between January 2020 and June 2021 were screened. Data were collected retrospectively from the electronic folder system. Data, including causes of mortality, recipient gender, age, transplant indication, presence of hepatocellular carcinoma, rejection episodes, number of days in the intensive care unit, hospitalization duration, and complications, were recorded. Patients with no PVT constituted the control group. Patients with PVT were considered as the study group. Student’s t-test and the Mann-Whitney U test were used to evaluate the significance of the difference between study groups. Overall, 223 liver transplants were performed within the study period. Three re-transplants were excluded from the study. The analysis of 220 liver transplant patients revealed that 18.2% (n=20) of the patients presented with a PVT before liver transplantation. Patients with PVT had a higher rate of non-alcoholic steatohepatitis as an indication of a liver transplant. In addition, the presence of PVT significantly increased surgical mortality and early rejection rates. In correlation with this, the intensive care unit stay was longer in the patient group with PVT. Although the early surgical mortality post-liver transplant was higher in the group with PVT, the underlying variables could not be identified in this study. Nevertheless, the late mortality rates were not higher in patients with PVT following liver transplantation

Presence of Hepatocellular Carcinoma Does Not Affect Course and Response to Anticoagulation of Bland Portal Vein Thrombosis in Cirrhotic Patients.

Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins. We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC. Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included. A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109). The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation.

Overestimated renal function in patients with liver cirrhosis predicts poor prognosis.

A high prevalence of overestimated renal function in patients with liver cirrhosis (LC) has been reported; nonetheless, its impact on prognosis remains unclear. We aimed to evaluate the impact of overestimated renal function on prognosis in patients with LC. An overestimated renal function was defined as a >20% increase in the creatinine-based estimated glomerular filtration rate (eGFR), compared with cystatin C-based eGFR. LC patients with conserved serum, who were evaluated for muscle atrophy and had proper clinical information were included, and their prognostic factors were analyzed. A total of 215 consecutive patients with LC were included. The prevalence of overestimated renal function was 29.8% (64/215). Kaplan-Meier survival analysis revealed that patients with overestimated renal function had a poorer prognosis than those without overestimated renal function (hazard ratio [HR]: 2.217 95% confidence interval [CI]: 1.290-3.810; p=0.001). Subgroup analysis showed that overestimated renal function was a significant prognostic factor, irrespective of sex and the presence of hepatocellular carcinoma (HCC). Multivariate Cox regression analyses revealed that overestimated renal function was a significant and independent factor predictive of poor prognosis in the entire cohort (HR: 2.050; 95% CI: 1.041-4.037; p=0.038) and in subgroups classified by Child-Pugh class A (HR: 2.131; 95% CI: 1.019-4.458; p=0.044), Model for End-Stage Liver Disease score ≤9 (HR: 2.303; 95% CI: 1.038-5.109; p=0.04), and presence of HCC (HR: 2.290; 95% CI: 1.128-4.651; p=0.022). Overestimated renal function is a significant and independent prognostic factor in patients with LC.

The role of CT liver perfusion in detecting predictors of portal vein thrombosis in patients with compensated and subcompensated liver cirrhosis

Portal vein thrombosis is one of the most common complications of liver cirrhosis, the risk factors for which are still not fully understood.Purpose: to develop a prognostic model to determine the likelihood of portal vein thrombosis based on anamnestic, etiological factors, the presence of hepatocellular carcinoma, as well as parameters of CT perfusion of liver tissue.Material and methods. 43 patients with compensated liver cirrhosis (58.1% of men) and 38 patients with subcompensated liver cirrhosis (50% of men) were included in the prospective study. The age of patients in the first group was 52.56 ± 9.62 years, in the second group - 50.95 ± 9.94 years. The number of patients with 1 etiological factor of liver cirrhosis in the study groups was 62.8% and 81.5%, respectively. Type 2 diabetes mellitus was exhibited in 23.3% of patients with compensated liver cirrhosis and in 15.8% of patients with subcompensated liver cirrhosis. The diagnosis of hepatocellular carcinoma was established in 27.9% of patients with compensated liver cirrhosis and in 18.4% of patients with subcompensated liver cirrhosis. All patients, after the native study, underwent CT perfusion of the liver using a 256-slice Philips ICT apparatus. As a result of postprocessing, the values of arterial, portal, total perfusion and perfusion index of liver tissue were determined. Statistical analysis of the data was carried out using the binary logistic regression method and the construction of ROC curves.Results. A logistic stepwise multivariate analysis showed that an increase in arterial perfusion (p = 0.002) and a decrease in portal perfusion (p = 0.004) were independently associated with portal vein thrombosis in patients with compensated liver cirrhosis, and a history of primary liver cancer (p &lt; 0.001) was a dependent factor in this model. In patients with subcompensated liver cirrhosis, a history of hepatocellular carcinoma (p &lt; 0.001) and a decrease in portal perfusion (p = 0.001) became independent predictors of portal vein thrombosis, male gender (p = 0.029) was a dependent factor in the developed model.Conclusion. CT-perfusion of the liver makes it possible to determine predictors that can be used together with such factors as the presence of hepatocellular carcinoma and gender in the construction of prognostic models to determine the likelihood of portal vein thrombosis in patients with compensated and subcompensated liver cirrhosis. Age, etiological factor and the presence of type 2 diabetes mellitus in the developed models were not statistically significant.

Clinical Outcomes of Liver Transplantation for Patients Over 60 Years Old: A Single-Center Experience.

Although advanced age is no longer considered an absolute contraindication for liver transplant, transplant in elderly patients with comorbid diseases remains debatable because of high risks with surgery. Here, we report patient outcomes in this population. We retrospectively reviewed medical records of 276 liver transplant recipients, grouped by age. Group 1 (≤59 years old) consisted of 247 recipients, and group 2 (≥60 years old) consisted of 29 recipients. Reviewed data included age, sex, cause of liver disease, presence of hepatocellular carcinoma, Child-Pugh and Model for End-Stage Liver Disease scores, survival, and posttransplant complications. In both groups, most patients (n = 108) required liver transplant for hepatitis B virus. Mean age was 40 ± 12.3 and 63 ± 2.3 years in groups 1 and 2, respectively, with more men than women in both group 1 (71.7% vs 28.3%) and group 2 (75.9% vs 24.1%). No significant differences were shown between groups for patient characteristics, except group 1 had significantly higher Model for End-Stage Liver Disease score. Group 1 mean survival time was 10.2 ± 0.6 years, with patient survival rates at 1, 5, 10, and 15 years of 65.5%, 53%, 46.3%, and 40%, respectively. In group 2, respective results were 10.6 ± 1.3 years and 75.9%, 68.6%, 61%, and 48.8% (no significant difference vs group 1). Liver transplant recipients >60 years of age had survival rates, acute rejection rates, and complications similar to younger recipients. Liver transplant should not be withheld from older recipients on the basis of age alone. However, comprehensive screening for comorbidities should be performed.

Enhancing the Quality of Follow-Up Care for Patients With Hepatitis B and C Using an Electronic Reminder System: A 2016-2019 Hospital-Based Study

&lt;p&gt;B、C型肝炎病人需要定期追蹤及檢驗疾病發展狀況，以及早發現肝癌。彰化基督教醫院胃腸肝膽科於2010年開始實行衛生福利部中央健康保險署（下稱健保署）追蹤照護計畫，過程中因病人病識感低，以及門診收案及追蹤流程複雜，截至2016年收案率14.6%、年度完整追蹤率28.8%，皆未達健保署設定的3項品質獎勵監測指標。透過E化之B、C肝照護管理系統，改善並簡化門診收案流程，提升個案管理師收案追蹤效率及提高病人遵從醫囑率，大幅提升了B、C肝病人照護品質。於2017年開始執行E化追蹤管理，2019年收案率提升至58.91%(4542/7710)，年度完整追蹤率達74.45%(3107/4173)。健保署評比2018年度品質獎勵榮獲中區第一名，本院是中區唯一獲得品質獎勵之醫學中心。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Patients with hepatitis B and C require regular follow-up to monitor disease activity and screen for the presence of hepatocellular carcinoma. Since 2010, Changhua Christian Hospital has implemented a hepatitis B and C care plan guided by the National Health Insurance Administration (NHIA), Ministry of Health and Welfare (MOHW). The rates of patient enrollment and follow-up between 2010 and 2016 were unsatisfactory. The annual enrollment and follow-up rates were only 14.6% and 28.8%, respectively, in 2016, falling below the three quality indicator standards established by the NHIA. The absence of insight into patient disease and the complexity of patient enrollment and follow-up procedures were identified as the main problems. Therefore, in 2017, we developed a strategy for improving and simplifying the patient enrollment process, enhancing the efficiency of the case managers involved in patient enrollment and follow-up, and increasing the rate of medical compliance. An electronic follow-up reminder system was implemented to enhance our quality of care among patients with hepatitis B and C. Thus, in 2019, the annual enrollment and follow-up rates had dramatically increased to 58.91% (4542/7710) and 74.45% (3107/4173), respectively. Because of the improved care management system, our hospital was the only medical center in central Taiwan that won an NHI Quality Award in 2018.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

The role of CT liver perfusion in detecting predictors of portal vein thrombosis in patients with compensated and subcompensated liver cirrhosis

Portal vein thrombosis is one of the most common complications of liver cirrhosis, the risk factors for which are still not fully understood.Purpose: to develop a prognostic model to determine the likelihood of portal vein thrombosis based on anamnestic, etiological factors, the presence of hepatocellular carcinoma, as well as parameters of CT perfusion of liver tissue.Material and methods. 43 patients with compensated liver cirrhosis (58.1% of men) and 38 patients with subcompensated liver cirrhosis (50% of men) were included in the prospective study. The age of patients in the first group was 52.56 ± 9.62 years, in the second group - 50.95 ± 9.94 years. The number of patients with 1 etiological factor of liver cirrhosis in the study groups was 62.8% and 81.5%, respectively. Type 2 diabetes mellitus was exhibited in 23.3% of patients with compensated liver cirrhosis and in 15.8% of patients with subcompensated liver cirrhosis. The diagnosis of hepatocellular carcinoma was established in 27.9% of patients with compensated liver cirrhosis and in 18.4% of patients with subcompensated liver cirrhosis. All patients, after the native study, underwent CT perfusion of the liver using a 256-slice Philips ICT apparatus. As a result of postprocessing, the values of arterial, portal, total perfusion and perfusion index of liver tissue were determined. Statistical analysis of the data was carried out using the binary logistic regression method and the construction of ROC curves.Results. A logistic stepwise multivariate analysis showed that an increase in arterial perfusion (p = 0.002) and a decrease in portal perfusion (p = 0.004) were independently associated with portal vein thrombosis in patients with compensated liver cirrhosis, and a history of primary liver cancer (p &lt; 0.001) was a dependent factor in this model. In patients with subcompensated liver cirrhosis, a history of hepatocellular carcinoma (p &lt; 0.001) and a decrease in portal perfusion (p = 0.001) became independent predictors of portal vein thrombosis, male gender (p = 0.029) was a dependent factor in the developed model.Conclusion. CT-perfusion of the liver makes it possible to determine predictors that can be used together with such factors as the presence of hepatocellular carcinoma and gender in the construction of prognostic models to determine the likelihood of portal vein thrombosis in patients with compensated and subcompensated liver cirrhosis. Age, etiological factor and the presence of type 2 diabetes mellitus in the developed models were not statistically significant.

Association Between ACOX1 and NRF1 Gene Expression and Hepatitis B and C Virus Infections and Hepatocellular Carcinoma in Liver Transplant Patients (Shiraz, Iran).

Liver transplantation is used to treat both patients with end-stage liver diseases and those with hepatocellular carcinoma; in Iran, these patients are commonly infected with hepatitis B and C viruses. In the present study, for the first time, we investigated the association between ACOX1 and NRF1 gene and protein expression and presence of hepatitis B virus, hepatitis C virus, and hepatocellular carcinoma in liver transplant patients in South-Central Iran. In this cross-sectional study, we included 200 patients who were seen between 2008 and 2017 for liver transplant at the Namazi Hospital, Shiraz University of Medical Sciences (Shiraz, Iran). All patients received liver grafts from brain dead donors. Donors and recipients were unrelated. ABO compatibility blood group analyses for donor-recipient pairs were conducted. Liver transplant recipients were divided into 3 different groups: hepatitis B virus infected, hepatitis C virus infected, and presence of hepatocellular carcinoma. We also had a control group that included 30 healthy individuals. NRF1 and ACOX1 gene expression levels were evaluated using the SYBER green real-time polymerase chain reaction method. NRF1 and ACOX1 protein expression levels were evaluated using enzymelinked immunosorbent analyses. We used SPSS software for statistical analyses (version 19.0). NRF1 gene expression was increased in all 3 liver transplant recipient groups compared with the control group (not significant, P > .05). Furthermore, ACOX1 gene expression was decreased in all patients compared with control (P > .05). However, we found ACOX1 and NRF1 protein expression to be significantly decreased in all 3 liver transplant recipients groups compared with the control group (P < .05). NRF1 and ACOX1 genes and their protein expressions could affect the development of chronic liver disease.

Minimal and Maximal Extent of Band Ligation for Acute Variceal Bleeding during the First Endoscopic Session.

Background/AimsThe appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session.MethodsWe retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events.ResultsMinimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure <90 mm Hg at initial presentation were also associated with treatment failure. In contrast, 30-day rebleeding and 30-day mortality did not differ between the minimal and maximal EVL groups.ConclusionsGiven that minimal EVL was associated with a high risk of treatment failure, maximal EVL may be a better option for variceal bleeding. However, the minimal EVL strategy should be considered in select patients because it does not affect 30-day rebleeding and mortality.

Low serum magnesium concentration is associated with the presence of viable hepatocellular carcinoma tissue in cirrhotic patients

This study aimed to ascertain, for the first time, whether serum magnesium (Mg) concentration is affected by the presence of hepatocellular carcinoma (HCC). We retrospectively enrolled consecutive cirrhotic patients with a diagnosis of HCC (n = 130) or without subsequent evidence of HCC during surveillance (n = 161). Serum levels of Mg were significantly (P < 0.001) lower in patients with HCC than in those without (median [interquartile range]: 1.80 [1.62–1.90] mg/dl vs. 1.90 [1.72–2.08] mg/dl). On multivariate logistic regression, low serum Mg was associated with the presence of HCC (OR 0.047, 95% CI 0.015–0.164; P < 0.0001), independently from factors that can influence magnesaemia and HCC development. In a subset of 94 patients with HCC, a linear mixed effects model adjusted for confounders showed that serum Mg at diagnosis of HCC was lower than before diagnosis of the tumor (β = 0.117, 95% CI 0.039–0.194, P = 0.0035) and compared to after locoregional treatment of HCC (β = 0.079, 95% CI 0.010–0.149, P = 0.0259), with two thirds of patients experiencing these changes of serum Mg over time. We hypothesize that most HCCs, like other cancers, may be avid for Mg and behave like a Mg trap, disturbing the body’s Mg balance and resulting in lowering of serum Mg levels.

Safety of direct oral anticoagulants in patients with advanced liver disease.

Background & AimsWhile direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited.MethodsLiver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low‐molecular‐weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti‐Xa peak levels and thrombomodulin‐modified thrombin generation assays (TM‐TGAs) were measured in a subgroup of 35/28 DOAC patients.ResultsAmong patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child‐Pugh‐stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure‐related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow‐up of 10.5 (IQR: 4.0‐27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS‐B/C (at 12 months: 36.9% vs CPS‐A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59‐6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00‐16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82‐9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti‐Xa peak levels were higher in patients with CPS‐B/C (345 [95% CI: 169‐395] vs CPS‐A: 137 [95% CI: 96‐248] ng/mL, P = .048) and were associated with lower TM‐TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients.ConclusionsAnticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.

Survival Analysis of Hospitalized Liver Cirrhotic Patients in Jakarta: 2 Years Follow Up Study

Background: The incidence of liver cirrhosis in Indonesia is increasing over time. In this study, we aim to present a 2-year survival analysis on liver cirrhotic patients using Child-Pugh and MELD score and also analyzing the most common cause of death among liver cirrhotic patients.Method: A retrospective cohort study was used by evaluating the medical records of patients who went to internal medicine ward of Cipto Mangunkusumo Hospital during the period between 2011-2016. The inclusion criteria were all cirrhotic patient registered with a completely filled medical record. The exclusion criteria were the presence of Hepatocellular carcinoma, cholangiocarcinoma, and other form of malignanciesResults: A total of 89 patients were included in this study. The total of 75.3% of the patients were dead during the 2 years follow up with the most prevalent cause of death (COD) being infection (45.5%). Survival analysis, showed that the survival of CP Class A were significantly better than B and C. The cut off value for 2-years mortality was CP score 7 and MELD score 9 in liver cirrhotic patientsConclusion: The mortality rate of liver cirrhotic patients is very high with infection as the main COD. Patients with Child-Pugh score B and C have worse prognosis than Child-Pugh score A.

Moderately Macrosteatotic Livers Have Acceptable Long-Term Outcomes but Higher Risk of Immediate Mortality

Liver transplantation is the most effective treatment for end-stage liver disease (ESLD). Whether moderately macrosteatotic livers (30%-60%) represent a risk for worsened graft function is controversial. The uncertainty, in large part, is owing to the heterogeneous steatosis grading. Our aim was to determine the short- and long-term outcomes of moderately macrosteatotic allografts that were graded according to a standardized institutional protocol. We performed a retrospective analysis of transplants performed between 1994 and 2014. All patients with allografts biopsied pretransplantation were included. Relevant donor and recipient variable were recorded. Moderately macrosteatotic livers were compared with mildly macrosteatotic and nonsteatotic livers. Primary outcomes of interest were patient survival at 90 days, 1 year, and 5 years. Cox regression analyses were carried out to compare survival between the 2 groups. We compared 65 allografts with moderate macrosteatosis and 810 with no or mild macrosteatosis. Patients with moderately macrosteatotic allografts were 2.69 times as likely to die within the first 90 days after transplant (75.1% vs 91.6% survival) after adjusting for donor age, donor race, recipient age, recipient race, recipient body mass index, recipient diabetes, presence of hepatocellular carcinoma, days on waitlist, Model for End-Stage Liver Disease (MELD) score at transplantation, cold ischemia time. However, for recipients who survive 90 days, moderately macrosteatotic allografts had comparable long-term survival. Our study shows that moderate macrosteatosis is a strong predictor of early but not late mortality. Further studies are needed to distinguish the specific cohort of patients for whom moderately macrosteatotic allografts will lead to acceptable outcomes.