Association of statins with nonalcoholic fatty liver disease in patients with diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in patients with diabetes; limited data suggested that statins may reduce the risk of NAFLD progression. This study aimed to examine the association between statins and the development or progression of NAFLD in veterans with diabetes. In a new-user negative control design, we conducted a retrospective propensity score (PS)-matched cohort study of patients with diabetes between 2003 and 2015. After excluding patients with other causes of liver disease, we formed PS using 85 characteristics. The primary outcome was a composite NAFLD progression outcome. Primary analysis examined odds of outcome in PS-matched cohort. Post-hoc analysis included a PS-matched cohort of statin users with intensive lowering of low-density lipoprotein-cholesterol (LDL-C) vs low-intensity lowering. We matched 34,102 pairs from 300,739 statin users and 38,038 non-users. The composite outcome occurred in 8.8% of statin users and 8.6% of non-users (odds ratio (OR) 1.02, 95% confidence interval (95% CI) 0.97-1.08). In the post-hoc analysis, intensive lowering of LDL-C compared to low-intensity showed increased NAFLD progression (OR 1.21, 95% CI 1.13-1.30). This study showed that statin use in patients with diabetes was not associated with decreased or increased risk of NAFLD progression. Intensive LDL-C lowering, compared to low-intensity LDL-C lowering, was associated with an increased risk of NAFLD progression.

Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice.

Background: Most advanced hepatocellular carcinoma (HCC) cases administered molecular targeted agents and/or anti-programmed cell death-1 (PD-1) inhibitors have no response or develop resistance. Moreover, second-line therapies still cannot provide beneficial clinical outcomes. A pilot study assessing combined regorafenib and PD-1 inhibitor as second-line treatment of advanced HCC reported promising effectiveness. Methods: The current single-center, retrospective, real-world study was carried out between January 2019 and July 2021. Advanced HCC cases were administered second-line regorafenib combined with a PD-1 inhibitor or regorafenib alone were assessed. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were determined. Results: Totally 46 HCC cases were analyzed, most of whom underwent previous systemic treatment comprising targeted therapy and immunotherapy. Tumor response was evaluated in 25 and 21 individuals in the regorafenib + PD-1 inhibitor and regorafenib monotherapy groups, respectively: ORRs were 21.7% and 8.7%, and DCRs were 47.8% and 32.6%, respectively. Median PFS was markedly longer in the regorafenib plus PD-1 inhibitor group (11.5 months) compared with the regorafenib monotherapy group (5.1 months, P=0.049). Conclusions: This study suggested regorafenib and a PD-1 inhibitor in combination may provide significant clinical benefits in HCC cases showing progression following first-line treatment. Further analysis in real-world studies with large cohorts is warranted to confirm these findings.

Baseline Albumin-Bilirubin grade as a predictor of response and outcome of regorafenib therapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The use of regorafenib in the treatment of hepatocellular carcinoma (HCC) is widespread. Albumin-Bilirubin (ALBI) has been shown to be a potential prognostic marker for regorafenib treatment, but its prognostic value remains controversial. Therefore, we conducted a meta-analysis to investigate the value of the baseline ALBI grade in predicting the efficacy and survival outcomes of HCC patients after regorafenib treatment. METHODS: PubMed, Embase, Cochrane library, Web of Science, CNKI, Wan Fang Data, and Vip Database were searched from January 2010 to October 2022. Studies treating HCC patients with regorafenib and with ALBI as a categorical variable, overall survival (OS) and progression-free survival (PFS) as outcome indicators were included. After applying Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included studies, Review Manager 5.4 was used to statistically analyze. Chi-square Q test and I2 statistics were used to detect heterogeneity. Funnel plot asymmetry, Egger's and Begg's test were used to evaluate publication bias. RESULTS: A total of 12 studies, comprising 1,918 patients, were included in the meta-analysis. The included studies were all evaluated as high quality. Compared to the high-grade baseline ALBI group, patients in the low-grade group had a longer survival time after receiving regorafenib and also more suitable for regorafenib treatment [odds ratio (OR) = 6.50, 95% confidence interval (CI): 2.22-18.96, P < 0.01]. The low-grade baseline ALBI group before sorafenib treatment was significantly correlated with better OS [hazard ratio (HR) = 2.36, 95% CI: 1.68-3.31, P < 0.00001] and PFS (HR = 1.56, 95% CI: 1.16-2.08, P = 0.003). Likewise, the low-grade baseline ALBI group before regorafenib was also significantly correlated with better OS (HR = 1.56, 95% CI: 1.15-2.13, P = 0.005) and PFS (HR = 2.06, 95% CI: 1.37-3.11, P = 0.0005). In addition, the ALBI grade was significantly correlated with disease control rate (DCR) (OR = 2.90, 95% CI: 1.45-5.79, P = 0.003), but not the objective response rate (OR = 1.98, 95% CI: 0.71-5.46, P = 0.19). CONCLUSIONS: The baseline ALBI grade could be a valuable prognostic indicator for predicting response and outcomes in HCC patients treated with regorafenib.

Fibrosing Cholestatic Hepatitis Masquerading Acute Rejection in Hepatitis C Virus-Positive Donor Liver Graft.

Fibrosing cholestatic hepatitis is a rare complication that manifests in patients receiving organ transplantation from seropositive (hepatitis C virus or hepatitis B virus) donors. We report a rare case of such a phenomenon in the immediate post-transplant period.

N6-Methyladenosine Modification of ANLN Enhances Hepatocellular Carcinoma Bone Metastasis.

Bones are categorized as the second most prevalent location of extra-hepatic metastasis in Hepatocellular Carcinoma (HCC), which is linked to an extremely poor prognosis due to limited therapeutic options. N6-methyladenosine (m6A) is a prominent modification involved in HCC, but the exact mechanisms on how m6A modifications induce HCC bone metastases (BM) remain unclear. The key modulators responsible for the abundant m6A RNA modification-induced HCC BM was found to be the METTL3 and YTHDF1. The expression of Anillin actin-binding protein (ANLN) was dramatically higher in HCC with BM tissues, and its messenger RNA (mRNA) stability was enhanced via m6A epitranscriptomic regulation by METTL3 and YTHDF1. High METTL3 and YTHDF1 expression along with nuclear ANLN protein was clinically correlated with BM in HCC patients. Furthermore, HCC BM was attributed to over-expression of nuclear ANLN forming a transcriptional complex with SP1 which enhanced KIF2C transcriptional activity to activate the mTORC1 pathway, therefore increased the expression of RANKL and disproportionated RANKL-OPG expression in bone microenvironment leading to malignant neoplasms invade bone tissue. In addition, inhibition of ANLN m6A modification by DZNeP attenuated HCC BM. This data provides meaningful understanding of the modulation and association of m6A epitranscriptomic-regulated BM in HCC, and moreover, defines potentially valuable therapeutic targets.

A Novel Mutation in the ATP7B Gene: A Rare Manifestation of Wilson Disease With Liver Failure.

Wilson disease is a hereditary disorder which involves anomalous copper metabolism. Typically, the presentation is systemic, involving vital organs such as the liver, kidney, and brain, among others. We report a unique case presenting with solitary organ involvement as acute liver failure with novel ATP7B gene mutation, which has never been reported before.

COVID-19 vaccination-related hemophagocytic lymphohistiocytosis presenting as acute liver failure.

Acute liver failure following COVID-19 infection and/or vaccination is very rare and can be secondary to hemophagocytic lymphohistiocytosis (HLH). Liver injury in such cases appears to be extrinsic and thus treatment hinges on prompt diagnosis and reversal of the primary disease. We describe a patient who developed acute liver failure secondary to HLH after receiving a second dose of the Pfizer COVID-19 vaccine. Persistently elevated liver function tests, fevers, and cytopenia following COVID-19 vaccination should prompt clinicians to calculate an H-score to evaluate for the presence of HLH.

Assessing the Educational Value of Pancreatic Cancer Videos on YouTube®.

Online resources such as YouTube® can serve as the go-to resource for patients and their caregivers after a life-changing diagnosis of pancreatic cancer. There is a need to analyze the content and educational value of these videos for patients with pancreatic cancer. The top 100 most viewed videos on pancreatic cancer on YouTube® were assessed and data were collected on various variables such as views, likes, dislikes, and comments. Videos categorized as patient educational videos were further analyzed for their content, source, and educational value. Videos uploaded by patients were the most discussed (p = 0.014) and liked (p = 0.0028) videos on YouTube®. The content of the videos (personal experience, advertisement, patient education, medical professional education, alternative treatments, and increased pancreatic cancer awareness) varied depending on the uploader (patients, healthcare providers, professional societies, media) of the videos (p = 0.0007). Patient education videos were poor in being comprehensive on their education of pancreatic cancer based on our rubric (mean score of 7.67 ± 2.63 of 20 possible points). The current study shows that the educational values of YouTube® videos related to pancreatic cancer remain limited. There is significant room for healthcare providers to use the platform to develop and share comprehensive videos that can be used as more effective sources of patient education.

The non-coding RNA (ncRNA)-mediated high expression of polycomb group factor 1 (PCGF1) is a prognostic biomarker and is correlated with tumor immunity infiltration in liver hepatocellular carcinoma.

Background: Liver hepatocellular carcinoma (LIHC) has a poor prognosis worldwide. Polycomb group factor 1 (PCGF1) was recently reported to play a tumor suppressive role in cancers. However, the molecular mechanism and competitive endogenous ribonucleic acid (ceRNA) regulatory networks of PCGF1 in LIHC are still unclear. Methods: We constructed a PCGF1 ceRNA regulatory network in LIHC and identified potential prognostic markers, especially for tumor immunity. We identified the gene expression profiles and conducted correlation and survival analyses of PCGF1 and the related RNAs. We also explored the clinicopathological features and diagnostic and prognostic values of PCGF1 and constructed a nomogram to predict 1-, 3-, and 5-year survival. Based on a variety of bioinformatics tools, we confirmed the PCGF1-related signaling pathways in LIHC. Finally, the role of PCGF1 in immune cell infiltration was also analyzed. Results: We found that PCGF1 was overexpressed in LIHC (P<0.001) and was linked to a poor prognosis in terms of overall survival (OS, P=0.029), the progress-free interval (PFI, P=0.002), and disease-free survival (DFS, P=0.02). Hsa-miR-22-3p was highly negatively correlated with PCGF1. Further, 3 upstream long non-coding RNAs (lncRNAs) (i.e., AC016405.3, BX284668.6, and MIR4435-2HG) were confirmed to further research. PCGF1 was positively associated with pathologic tumor stages (P=0.001), histologic grade (P=0.030), alpha fetoprotein (AFP) level (P=0.030), and vascular invasion (P=0.022). The area under the curve of PCGF1 was 0.983 [confidence interval (CI): 0.972-0.994]. In the multivariate analyses, high PCGF1 expression remained an independent factor associated with OS [hazards ratio (HR): 1.696, P=0.027], DSS (HR: 2.139, P=0.024), and the PFI (HR: 1.512, P=0.034). We found that PCGF1 was involved in some malignancy-associated signaling pathways and plays a role in regulating the immune response. Conclusions: We confirmed the upstream ceRNA regulatory network of PCGF1 in LIHC. PCGF1 has an oncogenic effect and correlates with tumor immunity.

SLAMF1 is expressed and secreted by hepatocytes and the liver in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver disease in the United States and worldwide. Nonalcoholic steatohepatitis (NASH), the most advanced form of NAFLD, is characterized by hepatic steatosis associated with inflammation and hepatocyte death. No treatments are currently available for NASH other than lifestyle changes, and the disease lacks specific biomarkers. The signaling lymphocytic activation molecule family 1 (SLAMF1) protein is a self-ligand receptor that plays a role in orchestrating an immune response to some pathogens and cancers. We found that livers from humans and mice with NASH showed a more prominent immunohistochemistry staining for SLAMF1 than non-NASH controls. Furthermore, SLAMF1 levels are significantly increased in NASH plasma samples from mice and humans compared with their respective controls. In mice, the levels of SLAMF1 correlated significantly with the severity of the NASH phenotype. To test whether SLAMF 1 is expressed by hepatocytes, HepG2 cells and primary murine hepatocytes were treated with palmitic acid (PA) to induce a state of lipotoxicity mimicking NASH. We found that PA treatments of HepG2 cells and primary hepatocytes lead to significant increases in SLAMF1 levels. The downregulation of SLAMF1 in HepG2 cells improved the cell viability and reduced cytotoxicity. The in vivo data using mouse and human NASH samples suggests a potential role for this protein as a noninvasive biomarker for NASH. The in vitro data suggest a role for SLAMF1 as a potential therapeutic target to prevent hepatocyte death in response to lipotoxicity.NEW & NOTEWORTHY This study identified for the first time SLAMF1 as a mediator of hepatocyte death in nonalcoholic fatty liver disease (NASH) and as a marker of NASH in humans. There are no pharmacological treatments available for NASH, and diagnostic tools are limited to invasive liver biopsies. Therefore, since SLAMF1 levels correlate with disease progression and SLAMF1 mediates cytotoxic effects, this protein can be used as a therapeutic target and a clinical biomarker of NASH.

Cutaneous Manifestations in COVID-19-Positive African American Patients.

Background: The United States of America is the leading country in confirmed cases of and deaths from severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). In April and May 2020, respectively, 0.2% of patients in a Chinese COVID-19-positive cohort and 20.4% of patients in an Italian COVID-19-positive cohort developed cutaneous abnormalities. Cutaneous abnormalities associated with COVID-19 are not well documented or discussed, and investigation of cutaneous manifestations is necessary to determine if they have any clinical value. Methods: We conducted a retrospective study of COVID-19-positive patients who were admitted to Ochsner-Louisiana State University-Shreveport and Ochsner-Louisiana State University-Monroe facilities in Louisiana. Cutaneous manifestations were determined from clinical notes, descriptions in medical records, and a billing code for skin rashes. Results: Of 1,086 COVID-19-positive patients investigated, 871 were African American and 130 were Caucasian. Only 10 patents exhibited probable COVID-19-induced cutaneous abnormalities: 6 (0.7%) of the 871 African American patients and 4 (3.1%) of the 130 Caucasian patients. Dermatologic abnormalities included pruritic or erythematous rash and hypopigmentation of the face, upper chest, abdomen, and trunk areas. Our data are consistent with the smaller percentage of patients in the Chinese cohort study vs the larger percentage in the Italian cohort study. Conclusion: Our data provide evidence that cutaneous manifestations of COVID-19, especially in African American patients, are rare, but documentation of more cases is necessary to establish a cause and effect for COVID-19-induced skin manifestations.

Ferroptosis-related genes with post-transcriptional regulation mechanisms in hepatocellular carcinoma determined by bioinformatics and experimental validation.

Background: Ferroptosis is a form of iron-dependent cell death with increased free iron and massive lipid peroxidation. The discovery of ferroptosis offers insights into hepatocellular carcinoma (HCC) treatment. However, post-transcriptional regulation mechanisms of ferroptosis in HCC remain to be elucidated. The present study explored ferroptosis-related genes and their post-transcriptional regulation mechanisms in HCC. Methods: A ferroptosis score was computed in The Cancer Genome Atlas (TCGA) cohort via gene set variation analysis (GSVA), and ferroptosis-related genes were screened by differential expression and correlation analyses. CircRNA/miRNA-mediated ferroptosis-related genes were predicted, and associations of ferroptosis-related genes with m1A/m5C/m6A regulators were analyzed. Immune cell infiltrations were inferred via CIBERSORT. NUDCD1 expression was examined in L-02, SMMC7721, and HepG2 cells via real time quantitative polymerase chain reaction (RT-qPCR) and western blots. After NUDCD1 was silenced, cell viability, glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) expression, and oxidized glutathione/glutathione (GSSG/GSH) and glutathione (GSH) levels were detected in SMMC7721 and HepG2 cells. Results: The ferroptosis score was linked to poor overall survival (OS) of HCC, which was independent of other clinicopathological parameters. Ten ferroptosis-related genes were determined, namely UGT1A6, ATP6V1C1, MAFG, NUDCD1, PPP1R1A, TSKU, CTSB, AIFM2, CTSA, and CTNND2, which were post-transcriptionally regulated by circRNA/miRNA and m1A/m5C/m6A modifications in HCC. Most were significantly linked with most immune cell compositions within the immune microenvironment, and contributed to undesirable clinical outcomes. NUDCD1 was up-regulated in HCC cells, and its loss facilitated the ferroptosis of HCC cells. Conclusions: Overall, our findings determined ferroptosis-related genes post-transcriptionally regulated by circRNA/miRNA and m1A/m5C/m6A RNA modifications, and experiments demonstrated that loss of NUDCD1 may facilitate the ferroptosis of HCC cells, which provides novel insights into the regulatory mechanisms of ferroptosis in HCC.

Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.

Risk Stratification in Post-ERCP Pancreatitis: How Do Procedures, Patient Characteristics and Clinical Indicators Influence Outcomes?

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains common, and severe complications are associated with ERCP. There is no previous study detailing the effect of race and gender in a US-based population on risk of PEP. METHODS: Data were collected on 269 "first-performed" consecutive ERCPs followed by division by race (White vs. African-American) and sex (Female vs. Male). A total of 53 probable risk factors were evaluated by uni- and multivariate analysis followed by outcomes expressed as an odds ratio (OR) (with a 95% confidence interval, 95% CI). Finally, a principal component analysis was performed to construct a risk prediction model for PEP, which can be used by clinicians at bedside. RESULTS: After analyzing the risk factors based on race and gender-based groups, Caucasian males with PEP are more likely to have prior history of pancreatitis (p = 0.009), lower hemoglobin (p = 0.02)/blood urea nitrogen (BUN) (p = 0.01)/creatinine before ERCP (p = 0.07) and lower BUN (p = 0.01)/creatinine after ERCP (p = 0.07), while Caucasian females with PEP are more likely to have higher white blood cell (WBC) count before ERCP (p = 0.08) and lower amylase (p = 0.10)/bilirubin (p = 0.09)/aspartate aminotransferase (AST) after ERCP (p = 0.08). African-American males with PEP are more likely to have lower weight (p = 0.001)/smaller height (p = 0.0005)/lower alkaline phosphatase (p = 0.002)/AST (p = 0.04)/alanine transaminase (ALT) (p = 0.03) before ERCP and lower alkaline phosphatase (p = 0.002)/AST (p = 0.01)/ALT (p = 0.004) after ERCP, while African-American females with PEP are more likely to have prior history of pancreatitis (p = 0.004)/higher lipase before (p = 0.0001) and after (p = 0.05) ERCP along with increased risk with pancreatic duct cannulation (p = 0.0001) and injection (p = 0.0001)/biliary sphincterotomy (p = 0.0001). Importantly, prior history of ERCP, elevated AST after ERCP, and BUN prior to ERCP were found to be important clinical features predicting post-ERCP pancreatitis. To our knowledge, this is a first known attempt at developing a risk scoring system for PEP in a US population with decision tree learning. CONCLUSIONS: It is very evident that both patient and procedure-related risk factors vary by race and gender in the US population, leading to the development of a new risk assessment tool for PEP that can be used in clinical practice. We need to follow up with a larger prospective study to validate this novel race and gender-based risk scoring system for PEP.

Clinical Presentation of Hepatocellular Carcinoma in African Americans vs. Caucasians: A Retrospective Analysis.

Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008-2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.

Performance of echocardiography for detection of portopulmonary hypertension among liver transplant candidates: Meta-analysis.

BACKGROUND: Evaluation of pulmonary arterial pressure is crucial among cirrhotic patients, considering that moderate portopulmonary hypertension (POPH) is a contraindication for liver transplantation. Although right heart catheterization (RHC) is the most accurate method to diagnose POPH, it is invasive. OBJECTIVE: The aim of the study is to evaluate the performance of echocardiography in detecting POPH in liver transplant candidates. METHODS: A Literature search was performed, and pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and area under the summary receiver operating curve (AUC) were calculated. Subgroup analyses were performed based on different cutoff values for echocardiography and diagnostic criteria of RHC. RESULTS: Sensitivity, specificity, positive LR, negative LR, and AUC of echocardiography for detection of POPH were 0.86 (0.74, 0.94), 0.87 (0.84, 0.90), 7.17 (3.59, 14.31), 0.22 (0.13, 0.38), and 0.807 while they were 0.82 (0.74, 0.89), 0.81 (0.78, 0.84), 117.75 (16.03, 865.08), 0.28 (0.16, 0.50), and 0.876for detection of moderate POPH, respectively. Performance of echocardiography was not significantly different in the subgroup analyses of stringency of POPH criteria and pulmonary arterial systolic pressure (ePASP) cutoffs. CONCLUSIONS: Our meta-analysis supports utilization of echocardiography for screening of POPH. However, RHC remains essential in highly suspicious cases. Echocardiographic data other than ePASP should be evaluated in future studies.

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.

Cholestatic liver diseases: An era of emerging therapies.

Recently the field of cholestasis has expanded enormously reflecting an improved understanding of the molecular mechanisms underlying bile secretion and its perturbation in chronic cholestatic disease. Novel anti-cholestatic therapeutic options have been developed for patients not favorably responding to ursodeoxycholic acid (UDCA), the current standard treatment for cholestatic liver disease. Important novel treatment targets now also include nuclear receptors involved in bile acid (BA) homoeostasis like farnesoid X receptor and G protein-coupled receptors e.g., the G-protein-coupled BA receptor "transmembrane G coupled receptor 5". Fibroblast growth factor-19 and enterohepatic BA transporters also deserve attention as additional drug targets as does the potential treatment agent norUDCA. In this review, we discuss recent and future promising therapeutic agents and their potential molecular mechanisms in cholestatic liver disorders.

Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection Is Associated With Increased Survival in Patients With a History of Hepatocellular Carcinoma.

BACKGROUND & AIMS: There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC who achieved a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy, from January 2013 through December 2017 at 31 health care systems throughout the United States and Canada. We used Cox proportional hazards regression to determine the association between receipt of DAA therapy, modeled as a time-varying covariate, and all-cause mortality, accounting for informative censoring and confounding using inverse probability weighting. RESULTS: Of 797 patients with HCV-related HCC, 383 (48.1%) received DAA therapy and 414 (51.9%) did not receive treatment for their HCV infection after complete response to prior HCC therapy. Among DAA-treated patients, 43 deaths occurred during 941 person-years of follow-up, compared with 103 deaths during 526.6 person-years of follow-up among patients who did not receive DAA therapy (crude rate ratio, 0.23; 95% confidence interval [CI], 0.16-0.33). In inverse probability-weighted analyses, DAA therapy was associated with a significant reduction in risk of death (hazard ratio, 0.54; 95% CI, 0.33-0.90). This association differed by sustained virologic response to DAA therapy; risk of death was reduced in patients with sustained virologic response to DAA therapy (hazard ratio, 0.29; 95% CI, 0.18-0.47), but not in patients without a sustained virologic response (hazard ratio, 1.13; 95% CI, 0.55-2.33). CONCLUSIONS: In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.

Autoimmune Hepatitis (AIH) in Acquired Immune Deficiency Syndrome (AIDS): A Case Report and Review of Literature.

The common causes of abnormal liver chemistries in human immunodeficiency virus (HIV) infected patients are multifactorial. Diagnosis of autoimmune hepatitis (AIH) in HIV infected patients is intriguing but data is scarce. Unmasking of AIH during immune reconstitution in HIV patients after starting antiretroviral therapy is reported but not with advanced acquired immunodeficiency syndrome (AIDS). Here we present a fascinating case of 32-year-old African-American man with advanced AIDS who presented with elevated transaminases. He was diagnosed with AIH before starting antiretroviral therapy and successfully treated with prednisolone and azathioprine with antiretroviral therapy despite very low CD4 count.