Risk Of Liver Decompensation Research Articles

Immune Response and Risk of Decompensation following SARS-CoV-2 Infection in Outpatients with Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

Severe obesity is associated with worse outcomes than lean metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with obesity. We aimed to study the association of body mass index (BMI) with clinical outcomes in patients with MASLD. A retrospective cohort of 32,900 patients with MASLD, identified through the International Classification of Diseases-9 and 10 codes within the electronic health records of a large US-based health system, with a mean follow-up of 5.5 years (range: 1-15y), was stratified into 6 BMI categories, <25, 25-<30, 30-<40, 40-<50, and ≥50kg/m2. The risk of liver decompensation and extrahepatic obesity-associated cancers had a J-shaped profile (both ps for linear and quadratic terms <0.05). Compared to patients with BMI 25-<30kg/m2, the adjusted HRs (95% CIs) for liver decompensation of patients with BMI <25 and BMI ≥50kg/m2 were 1.44 (1.17-1.77) and 2.27 (1.66-3.00), respectively. The corresponding figures for obesity-associated extrahepatic cancer were 1.15 (0.97-1.36) and 1.29 (1.00-1.76). There was an inverse association for BMI with liver transplantation and non-obesity-associated cancer (both ps for linear terms <0.05), but no association with HCC or all types of cancers combined. A similar J-shaped association between BMI and all-cause mortality was observed; adjusted HRs (95% CIs) for BMI <25 and ≥50kg/m2 were 1.51 (1.32-1.72) and 3.24 (2.67-3.83), respectively, compared with BMI 25-<30kg/m2 (both ps for linear and quadratic terms <0.001). Patients with MASLD and very severe obesity (BMI ≥50kg/m2) had the highest risk, exceeding that of patients with lean MASLD, for developing liver decompensation, obesity-associated extrahepatic cancers, or dying from any cause.

The Impact of Portal Hypertension Assessment Method on the Outcomes of Hepatocellular Carcinoma Resection: A Meta-Analysis of Matched Cohort and Prospective Studies.

Examine portal hypertension (PHT) impact on postoperative and survival outcomes in hepatocellular carcinoma (HCC) patients after liver resection (LR), specifically exploring distinctions between indirect signs and invasive measurements of PHT. PHT has historically discouraged LR in individuals with HCC due to the elevated risk of morbidity, including liver decompensation (LD). A systematic review was conducted using 3 databases to identify prospective-controlled and matched cohort studies until December 28, 2022. Focus on comparing postoperative outcomes (mortality, morbidity, and liver-related complications) and overall survival in HCC patients with and without PHT undergoing LR. Three meta-analysis models were utilized: for aggregated data (fixed-effects inverse variance model), for patient-level survival data (one-stage frequentist meta-analysis with gamma-shared frailty Cox proportional hazards model), and for pooled data (Freeman-Tukey exact and double arcsine method). Nine studies involving 1124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with hepatic venous pressure gradient (HVPG) ≥10mmHg significantly increased the risk of overall complications, PHLF, and LD. Despite elevated risks, the procedure resulted in a 5-year overall survival rate of 55.2%. Open LR significantly increased the risk of overall complications, PHLF, and LD. Conversely, PHT did not show a significant association with worse postoperative outcomes in minimally invasive LR. LR in the presence of indirect signs of PHT poses no increased risk of complications. Yet, in HVPG ≥10mmHg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions. Minimally invasive approach seems to be vital for favorable outcomes, especially in HVPG ≥10mmHg patients.

Risk of acute liver injury following the nirmatrelvir/ritonavir use.

Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reported as adverse events of nirmatrelvir/ritonavir users in the EPIC-HR trial. To quantify the risk and severity of acute liver injury (ALI) associated with nirmatrelvir/ritonavir use. This self-controlled case-series study was conducted using electronic medical records of patients with confirmed diagnosis of SARS-CoV-2 infection between 26th February 2022 and 12th February 2023 in Hong Kong. Among 2 409 848 patients with SARS-CoV-2 infection during the study period, 153 853 were prescribed with nirmatrelvir/ritonavir, of whom 834 (.5%) had incident ALI (moderate: 30.5%; moderate to severe: 18.9%; severe or fatal: 5.8%). Compared with the non-exposure period, risk of ALI increased significantly during the pre-exposure period (IRR = 38.13, 95% CI = 29.29-49.62) and remained elevated during the five-day nirmatrelvir/ritonavir treatment (IRR = 20.75, 95% CI = 17.06-25.25) and during wash-out period (IRR = 16.27, 95% CI = 13.23-20.01). Compared to the pre-exposure period, risk of ALI was not increased during the five-day nirmatrelvir/ritonavir treatment period (IRR = .54, 95% CI = .43-.70). Compared to 5469 non-nirmatrelvir/ritonavir users with incident ALI, nirmatrelvir/ritonavir users had less severe ALI by the severity index (p < .001) and peak INR (1.7 vs. 2.3; p < .001). ALI cases with nirmatrelvir/ritonavir use had lower risk of all-cause death (29.1% vs. 39.1%; OR = .64; p < .001) and no increase in risk of liver decompensation (1.0% vs. 1.3%; OR = .62; p = .230) compared to non-users. The risk of ALI associated with nirmatrelvir/ritonavir treatment for COVID-19 was elevated in the pre-exposure period, but not following nirmatrelvir/ritonavir initiation. ALI following nirmatrelvir/ritonavir treatment were mostly mild and less severe than ALI events in non-nirmatrelvir/ritonavir users.

Chronic Liver Disease and Cirrhosis are Associated with Worse Outcomes Following SARS-CoV-2 Infection

Studies evaluating the impact of SARS-CoV-2 on chronic liver disease (CLD) are limited and have focused mostly on hospitalized patients or those with cirrhosis. We aim to evaluate the impact of underlying CLD on patient outcomes following COVID-19 using a one of the largest COVID-19+CLD cohorts to date. Data from the COVID-19 Research Database (https://covid19researchdatabase.org) were evaluated from 4/1/2020-8/31/2021 to determine whether concurrent CLD was associated with worse outcomes within 30-days of COVID-19 diagnosis, including need for hospitalization, pneumonia, severe pneumonia, respiratory failure, and multi-organ failure. Among patients with COVID-19+CLD, risks of liver decompensation and acute on chronic liver failure (ACLF) were evaluated, stratified by presence of cirrhosis. Adjusted multivariate logistic regression models evaluated the impact of CLD on COVID-19 outcomes. 1,208,905 unique patients with COVID-19 were identified; 44,008 (3.6%) had concurrent CLD, among which 6,515 (14.8%) had cirrhosis. Compared to patients without CLD, COVID-19+CLD patients were significantly more likely to require hospitalization (aOR 1.65, 95% CI 1.61-1.69), develop pneumonia (aOR 1.11, 95% CI 1.08-1.14), severe pneumonia (aOR 1.74, 95% CI 1.62-1.86), respiratory failure (aOR 1.14, 95% CI 1.10-1.17), and multi-organ failure (aOR 1.84, 95% CI 1.72-1.97), p<0.0001 for all. Among COVID-19+CLD patients, underlying cirrhosis was associated with even higher risk of these poor outcomes, and higher risk of acute liver decompensation or ACLF. Among one of the largest studies to date evaluating patients with COVID-19 and CLD, underlying CLD is associated with significantly greater risk of poor outcomes following SARS-CoV-2 infection, particularly among cirrhotic patients.

Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis

ObjectiveIn retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed...

CHESS-ALARM score to stratify decompensation risk in compensated advanced chronic liver disease patients: An international multicenter study.

A combination of platelet and elastography (PE criteria) was proposed to identify compensated advanced chronic liver disease (cACLD) patients at risk of liver decompensation. We aim to validate and refine PE criteria by developing a new predictive score to predict decompensation in Asian cACLD patients. An international cohort of 633 cACLD patients with liver stiffness measurement (LSM) and esophagogastroduodenoscopy performed were included. We validated PE criteria to predict first liver decompensation using competing risk analysis, with death and hepatocellular carcinoma as competing events. We developed a predictive model using proportional subdistribution hazard regression. Prognostic accuracy was compared with the model of end-stage liver disease (MELD), albumin-bilirubin (ALBI), and ALBI-FIB-4 score using time-dependent area under operative characteristic curve (tAUC). Sixty patients developed decompensation over the median follow-up of 39months. Favorable Baveno VI status ruled out cACLD patients at risk of liver decompensation. LSM>25kPa was suboptimal to predict cACLD patients who will develop liver decompensation. We developed CHESS-ALARM score by incorporating age, platelet, and gender into LSM. CHESS-ALARM score (tAUC=0.86, 95% confidence interval [CI]: 0.79-0.94) has significantly higher accuracy than MELD (tAUC: 0.61), ALBI (tAUC: 0.62), ALBI-FIB-4 (tAUC: 0.70), and LSM>25kPa (tAUC: 0.54) to predict liver decompensation at 5years (P<0.05 for all). Patients with CHESS-ALARM score≥-0.37 had an 11-fold higher risk of decompensation (subdistribution hazard ratio=11.2, 95% CI: 5.1-24.5). CHESS-ALARM score can be readily incorporated into clinical practice of cACLD patients to estimate individual risk of liver decompensation; however, more data are required in morbidly obese cACLD patients of nonviral etiology.

Systemic therapies for hepatocellular carcinoma: the present and the future.

Hepatocellular carcinoma is diagnosed in more than half of all cases at unresectable stage when no potentially curative treatments are feasible. Since 2008, sorafenib had represented the only effective first line systemic therapy over the last decade until the approval of lenvatinib, who showed to be non-inferior to sorafenib. Recently, for the first time, a combination of immunotherapy and antiangiogenic drug, atezolizumab plus bevacizumab, was associated with a significantly longer overall survival and progression free survival compared to sorafenib, becoming the new best performing first-line approach for unresectable HCC. After several randomized controlled trials (RCTs) that have attempted to find an effective second-line therapy, regorafenib, cabozantinib, ramucirumab, nivolumab and pembrolizumab represent approved treatments for patients who failed first-line treatment. However, inclusion criteria of second-line RCTs are quite heterogeneous and no direct comparisons exist among these agents. Exciting opportunities have been found either in the combination or in the sequencing of these agents, but the optimal therapeutic strategy for these patients remains elusive. Moreover, the coexistence of cirrhosis and the competing risk of liver decompensation increase the complexity of the assessment of the net health benefit of the available therapeutic approaches. The aim of this review is to summarize the evidence on systemic treatments for unresectable HCC and to explore the future perspectives on this topic.

Prevalence of liver injury and correlation with clinical outcomes in patients with COVID-19: systematic review with meta-analysis.

Liver involvement of SARS-CoV-2 infection has been reported in several papers, but without homogeneous findings. We aimed to systematically review the prevalence of liver involvement in patients with SARS-CoV-2 infection at their hospital admission, and its correlation with disease severity and clinical outcomes in patients with or without pre-existing chronic liver disease. We systematically searched PubMed, Embase, Web of Science, Medline, PMC, clinical trial registries, and other Coronavirus family publications for studies reporting data on SARS-CoV-2 infection or COVID-19 and liver function tests (LFTs) alterations, as well as clinical course of patients with chronic liver disease or cirrhosis. Case reports, preprints, editorials, reviews were excluded. We also revised literature to describe the background of liver involvement during SARS-CoV-2 infection. 36 studies, including 20724 patients with SARS-CoV-2 infection, were included. The pooled prevalence of LFTs abnormalities at admission was 46.9% (AST 26.5%, ALT 22.8%, GGT 22.5%, ALP 5.7%, tBIL 8.0%). ALT, AST, tBIL were independent predictors of disease severity (ALT OR 1.54, 95% CI 1.17-2.03; AST OR 3.17, 95% CI 2.10-4.77; tBIL OR 2.32, 95% CI 1.18-4.58) and in-hospital mortality (ALT OR 1.48, 95% CI 1.12-1.96; AST OR 4.39, 95% CI 2.68-7.18; tBIL OR 7.75, 95% CI 2.28-26.40). Heterogeneity among studies was high. The few available data also reported that COVID-19 was associated with increased risk of liver decompensation and mortality in patients with liver cirrhosis. LFTs alterations were reported in up to 47% of unselected patients with COVID-19 and were associated with severe disease or in-hospital mortality. In cirrhotic patients, COVID-19 was associated with high risk of liver decompensation or mortality.

Safety and Efficacy of Bariatric Surgery in Cirrhosis Patients With Extreme Obesity.

To assess the safety and efficacy of bariatric surgery in patients with cirrhosis. Bariatric surgery may be a viable option for patients with cirrhosis and extreme obesity. However, the risk of liver decompensation after surgery is not thoroughly investigated. We conducted a case-controlled study with 106 obese patients with cirrhosis (cases) and 317 age, sex, body mass index-, and type of surgery-matched obese patients without cirrhosis (controls) who underwent bariatric surgery. Patients with cirrhosis were predominantly Child-Pugh class A (97%) with the diagnosis established prior to surgery in only 46%. In the cirrhosis group, there was no death in the first 30 days compared with 1 patient in the control group. At 90 days there was 1 death in the cirrhosis group but no additional deaths in the control group. In total, 12 months after the surgery, there were 3 deaths in the cirrhosis group and 1 in the control group (2.8% vs 0.6%, P = 0.056). The surgery-related length of stay was significantly longer in patients with cirrhosis (3.7 ± 4.0 vs 2.6 ± 2.4 d, P = 0.001), but the 30-day readmission rate was lower (7.5% vs 11.9%, P = 0.001). The percent of total weight loss at 30 and 90-days was not significantly different between the groups and remained that way even at 1 year (29.1 ± 10.9 vs 31.2 ± 9.4%, P = 0.096). Bariatric surgery in obese cirrhotic patients is not associated with excessive mortality compared with noncirrhotic obese patients.

Effect of Using Direct Acting Anti-Virals In Treatment of HCV Naive Patient with and without Portal Hypertension

Abstract Background Hepatitis C Virus (HCV) infection is a major global health challenge; it is estimated that more than 80 million people are chronically infected worldwide. Egypt has the highest prevalence of HCV in the world (predominantly genotype 4) secondary to the previous schistosomiasis eradication campaigns with very high incidence rates among elderly, rural areas and in lower social classes. However, several oral anti-HCV drugs (direct acting antivirals; DAAs) have been developed over the last several years. Now, HCV can be eliminated from the infected host within 12 wk of DAA combination therapy without noticeable side effects Aims: to evaluate the Effect of presence of portal hypertension on the results of treatment of chronic HCV infected naive patient with direct acting antivirals Patients and Methods 200 subjects were divided into 2 groups: group I: including 100 cirrhotic patients with HCV infection and portal hypertension, group II: including 100 cirrhotic patients with HCV infection without portal hypertension. Diagnosis of portal hypertension was confirmed by presence of esophageal varices in endoscopy. Both group received combination of IFN-free DAAs. Results CK-18 was significantly elevated in patients of group I in comparison to group 11, with mean ± SD: 460 ± 279, 167 ± 56 and 149 ± 57, respectively, and P value: 0.001. with mean ±SD: 59.6± 28, when compared with control group (with 23±8) P value &amp;lt; 0.001. ROC curve between Cases and Control as regards CK18 with Area Under the Curve (AUC): 0.925. Cutoff &amp;gt; 30 ug/l With Sensitivity: 86.67% &amp; Specificity: 83.33%. Ck-18 was found to be correlated with steatosis and fibrosis assessed by fibroscan with P value&amp;lt; 0.001. Conclusion treatment of 200 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, regardless of whether the patients had EVs.

Low compliance with hepatocellular carcinoma screening guidelines in hepatitis B/C virus co-infected HIV patients with cirrhosis.

The incidence of hepatocellular carcinoma (HCC) in patients co-infected with HIV and hepatitis B virus (HBV) or hepatitis C virus (HCV) is increasing. In patients with cirrhosis, guidelines recommend HCC screening every 6 months. We assessed compliance with HCC screening guidelines in cirrhotic HBV/HCV-HIV-co-infected patients. HBV/HCV-HIV-co-infected patients with cirrhosis were enrolled from 4 European prospective cohorts participating in the COHERE collaboration, followed from 1 January 2005-1 January 2015. Assessment of liver cirrhosis was based on clinical diagnosis and liver biopsy or Fibroscan. Compliance with HCC screening guidelines was defined as one ultrasound every 6 months. Generalized estimating equation models adjusted for repeated measurements were fitted to determine predictors of low compliance. Different sensitivity analyses were performed and validation of the data was carried out by randomly checking 10% of each cohort's data. 646 HIV-patients with the diagnosis of cirrhosis were included: 518 (80%) HCV-, 85 (13%) HBV- and 43 (7%) HBV/HCV-co-infected. Median age at cirrhosis diagnosis was 44 years, median follow-up time since diagnosis was 5.3 years. Screening </=6 months was performed in 6-18% of individuals from 2005-2015. If the screening interval was increased to 9 or 12 months, compliance improved to 7-24% and 7-30% respectively. Thus, compliance with HCC screening guidelines in cirrhotic HIV-patients co-infected with HBV and/or HCV in Europe is low. In light of an ageing population and the increasing prevalence of liver cirrhosis this situation needs to be addressed urgently. This article is protected by copyright. All rights reserved.

Validation of a Model for Identification of Patients With Compensated Cirrhosis at High Risk of Decompensation

It is important to rapidly identify patients with advanced liver disease. Routine tests to assess liver function and fibrosis provide data that can be used to determine patients' prognoses. We tested the validated the ability of combined data from the ALBI and FIB-4 scoring systems to identify patients with compensated cirrhosis at highest risk for decompensation. We collected data from 145 patients with compensated cirrhosis (91% Child A cirrhosis and median MELD scores below 8) from a cohort in Nottingham, United Kingdom, followed for a median 4.59 years (development cohort). We collected baseline clinical features and recorded decompensation events. We used these data to develop a model based on liver function (assessed by the ALBI score) and extent of fibrosis (assessed by the FIB-4 index) to determine risk of decompensation. We validated the model in 2 independent external cohorts (1 in Dublin, Ireland and 1 in Menoufia, Egypt) comprising 234 patients. In the development cohort, 19.3% of the patients developed decompensated cirrhosis. Using a combination of ALBI and FIB-4 scores, we developed a model that identified patients at low vs high risk of decompensation (hazard ratio [HR] for decompensation in patients with high risk score was 7.10). When we tested the scoring system in the validation cohorts, the HR for decompensation in patients with a high-risk score was 12.54 in the Ireland cohort and 5.10 in the Egypt cohort. We developed scoring system, based on a combination of ALBI and FIB-4 scores, that identifies patients at risk for liver decompensation. We validated the scoring system in 2 independent international cohorts (Europe and the Middle East), so it appears to apply to diverse populations.

PNPLA3 Rs738409 C&amp;gt;G Variant Predicts Liver-Related Outcomes in Patients with Non-Alcoholic Fatty Liver Disease

Background: Patients with NAFLD are at higher risk of developing liver-related complications -liver decompensation(LD) and hepatocellular carcinoma (HCC), including death-. A single nucleotide polymorphism in PNPLA3 gene is associated with a higher prevalence of liver damage and HCC, but prospective date are not available. We aimed to assess whether the common rs738409 variant in PNPLA3 gene can predict the occurrence of liver-related events and death in a large cohort of NAFLD patients. Methods: We considered 471 consecutive Italian individuals with histological diagnosis of NAFLD or clinical diagnosis of compensated NAFLD-related cirrhosis, prospectively followed for at least 6 months. The occurrence of hepatic and extrahepatic outcomes was recorded (LD and HCC; cardiovascular events and extrahepatic cancers, overall and liver-related death). The rs738409 G>C polymorphisms was genotyped by TaqMan assay. Findings: During a median follow-up of 64.6 months 26 LD, 13 HCC and 16 deaths (12 liver-related) were recorded. All liver-related events including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. After adjusting for clinico-metabolic and histological risk factors PNPLA3 C>G variant was associated with a higher risk of LD(HR 2.10,95%C.I.1.03-4.29, p=0.04), HCC (HR 2.68,95%C.I.1.01-7.26, p=0.04) and liver-related death (HR 3.64, 5%C.I.1.18-11.2, p=0.02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis we confirmed the independent association of PNPLA3 variant with LD (HR 2.00,95%C.I.1.01-3.97, p=0.04), HCC (HR 2.66,95%C.I.1.02-7.13, p=0.04) and liver-related death (HR 3.64,95%C.I.1.18-11.2, p=0.02). No association was found between PNPLA3 genotype and cardiovascular events, extrahepatic cancers and overall mortality. Interpretations: Patients carrying PNPLA3 rs738409 G>C variant are at higher risk of developing liver-related events and death. Funding: None. Declaration of Interest: None. Ethical Approval: The study was carried out in accordance with the principles of the Helsinki Declaration, and with local and national laws. Approval was obtained from the AOUP “Giaccone” of Palermo.

An Update on the Clinicopathologic Features and Pathologic Diagnosis of Hepatitis E in Liver Specimens.

Infection with the hepatitis E virus (HEV) is globally seen a leading cause of hepatitis. Now increasingly recognized also in industrialized countries, hepatitis E constitutes a significant health problem worldwide. The patient's immune status determines the clinical course and histopathology of hepatitis E. In immunocompetent patients, hepatitis E usually follows an asymptomatic or subclinical course, but may also present with acute hepatitis. In contrast, immunocompromised patients may develop chronic hepatitis, and patients with preexisting liver diseases are at risk for liver decompensation with potentially fatal outcome. Whereas pathologists only occasionally encounter liver biopsies from immunocompetent individuals with hepatitis E, they are more likely exposed to biopsies from patients with preexisting liver disease or immunocompromised individuals. Histopathologic hallmarks of hepatitis E in immunocompetent patients comprise lobular disarray, lobular, and portal inflammation, as well as hepatocyte necrosis of varying extend and regeneration. Thus, it is similar to acute non-E viral hepatitis, yet further differential diagnoses include autoimmune hepatitis and drug-induced liver injury. Histopathologic findings of hepatitis E in preexisting liver disease are determined by the underlying pathology, but may be more severe. Histopathologic presentation of hepatitis E in immunocompromised patients is highly variable, ranging from minimal active hepatitis to chronic hepatitis with severe activity and progressive fibrosis. Taken together, the variability of the histologic features depending on the clinical context and the overlap with other liver diseases make the histopathologic diagnosis of hepatitis E challenging. Immunohistochemistry for HEV open reading frame 2 protein and molecular testing for HEV RNA are useful tissue-based ancillary tools.

Development of a prognostic score to predict response to Yttrium-90 radioembolization for hepatocellular carcinoma with portal vein invasion

Yttrium-90 transarterial radioembolization (TARE) has shown promising efficacy in the treatment of patients with hepatocellular carcinoma (HCC), associated with portal vein tumor thrombus (PVTT). The aim of this study is to identify prognostic factors for survival in patients with HCC and PVTT undergoing TARE, and build a prognostic classification for these patients. This is a single center retrospective study conducted over six years (2010-2015), on consecutive patients undergoing TARE. Patients were included if they met the following criteria: presence of at least one measurable HCC, presence of PVTT not occluding the main portal trunk, absence of extrahepatic metastases, Child-Pugh score within B7, Eastern Cooperative Oncology Group performance status 0-1. Uni- and multivariable analysis was used to explore the variables that showed an independent relationship with survival. A prognostic score was then derived, and three prognostic categories were identified. A total of 120 patients were included in the study. Median overall survival (OS) was 14.1 months (95% CI 10.7-17.5) and median progression-free survival (PFS) was 6.5 months (95% CI 3.8-9.2). The only variables independently correlated with OS were bilirubin, extension of PVTT and tumor burden. Three prognostic categories were identified: favourable prognosis (0 points), intermediate prognosis (2-3 points) and dismal prognosis (>3 points). Median OS in the three categories was 32.2 months, 14.9 months and 7.8 months respectively (p <0.0001). PFS (p = 0.045) and the risk of liver decompensation (p <0.0001) also significantly differed along the same prognostic categories. Radioembolization with Yttrium-90 is an effective therapy for patients with HCC and PVTT. The proposed prognostic stratification may help to better identify good candidates for the treatment, and those for whom TARE may be futile. Yttrium-90 transarterial radioembolization (TARE) is a microembolic procedure that minimizes alterations to hepatic arterial flow, and thus can be safely performed in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). In this study, we retrospectively evaluated the independent predictors of long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin level, extension of PVTT and tumor burden were independently related to post-treatment survival: the combination of these factors allowed us to build a prognostic stratification that may help to better identify good candidates for the treatment, and those for whom TARE may be futile.

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement.

BackgroundLiver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication.Patients and methodsThe study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p-value <0.05 was statistically significant.ResultsFollowing DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 (p<0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement (p=0.01) and APRI improvement (p=0.01) and 81% showed Fib-4 improvement (p=0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement.ConclusionSuccessful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV/hepatitis C virus coinfection.

Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs. Over 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71mo: HR, 2.27 [95% CI, 0.92-5.60]; >71mo: HR, 4.66 [95% CI, 1.04-20.83]; P=.045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71mo: HR, 3.04 [95% CI, 1.12-8.26]; >71mo: HR, 3.93 [95% CI, 0.75-20.50]; P=.030). These findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.

Hierarchic Interaction of Factors Associated With Liver Decompensation After Resection for Hepatocellular Carcinoma

Liver resection is the treatment of choice for hepatocellular carcinoma (HCC) in well-compensated liver cirrhosis. Postoperative liver decompensation (LD) is the most representative and least predictable cause of morbidity and mortality. To determine the hierarchy and interaction of factors associated with the risk for LD and to define applicable risk classes among surgical candidates. This retrospective review collected data from 543 patients with chronic liver disease who underwent hepatic resection for HCC from January 1, 2000, through December 31, 2013, in a tertiary comprehensive cancer center. Final follow-up was completed on January 31, 2015, and data were assessed from February 1 to 28, 2015. Preoperative prognostic factors and risk stratification for postoperative LD. Multivariate logistic regression was performed, and the independent risk factors for LD were included in a recursive partitioning analysis model. Results were validated by means of 10-fold cross-validation. The analysis included 543 patients, of whom 411 (75.7%) were male, 132 (24.3%) were female, and the median age was 68 (interquartile range, 62-73) years. An independent association with LD was found for major hepatectomy (odds ratio [OR], 2.41; 95% CI, 1.17-4.30; P = .01), portal hypertension (OR, 2.20; 95% CI, 1.13-4.30; P = .01), and Model for End-Stage Liver Disease (MELD) score greater than 9 (OR, 2.26; 95% CI, 1.10-4.58; P = .02). Recursive partitioning analysis confirmed portal hypertension as the most important factor (OR, 2.99; 95% CI, 1.93-4.62; P < .001), followed by extension of hepatectomy with (OR, 2.76; 95% CI, 1.85-4.77; P = .03) and without (OR, 2.98; 95% CI, 1.97-4.52; P < .001) portal hypertension, and MELD score (OR, 1.79; 95% CI, 1.23-2.13; P < .001). Low-risk patients (LD rate, 4.9% [11 of 226]) without portal hypertension underwent minor resection with a MELD score of 9 or less; intermediate-risk patients (LD rate, 28.6% [85 of 297]) had no portal hypertension and underwent major resections or, in case of minor resections, had portal hypertension or a MELD score greater than 9; and high-risk patients (LD rate, 60.0% [12 of 20]) underwent major resection with portal hypertension. Risk-class progression paralleled median length of stay (7, 8, and 11 days, respectively; P < .001) and liver-related mortality (4.4% [10 of 226], 9.0% [27 of 297], and 25.0% [5 of 20], respectively; P = .001). A 10-fold cross-validation of the model resulted in a C index of 0.78 (95% CI, 0.74-0.82) and an overall error rate of 0.06. The risk for postoperative LD after resection for HCC in chronic liver disease is associated with preoperative hierarchic interaction of portal hypertension, planned extension of hepatectomy, and the MELD score.

Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses.

Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC).A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment.Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration.Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC.