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.

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.

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.

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.

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.

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.

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.

Efficacy and safety of standard and anti-reflux self-expanding metal stent: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Self-expanding metal stents are the main palliative treatment modality for unresectable esophageal cancer. Gastroesophageal reflux is a common adverse outcome after placement of esophageal stent for cancer involving the gastroesophageal junction and the gastric cardia. Anti-reflux stents with valve have been designed to prevent the acid reflux. The superiority of anti-reflux stent over standard stent in preventing gastroesophageal reflux has not been established well. This study compares the anti-reflux stent and the standard stent in terms of their efficacy to prevent acid reflux. AIM: To compare the standard and the anti-reflux stents in terms of their efficacy, safety, and complications. METHODS: The meta-analysis included 8 randomized clinical trials (RCTs) to compare pooled outcomes of total 395 patients. Primary outcomes include improvement in reflux symptoms and dysphagia score. Secondary outcomes include complications of stent migration, occlusion, and bleeding. RESULTS: A total of eight RCTs were included in the meta-analysis. Compared to the standard stent, the anti-reflux stent showed a trend towards reduction in the dysphagia score without reaching a statistical significance [Standardized mean difference (SMD): -0.33 (-0.71, 0.05); P = 0.09, I 2: 37%]. There was no statistical difference in the gastrointestinal reflux (GER) scores between the two types of stents [SMD: -0.17 (-0.78, 0.45); P = 0.008, I 2: 74%]. Compared to standard stent, anti-reflux stent showed no difference in the risk of stent migration [OR: 1.37 (0.66, 2.83); P = 0.40, I 2: 0 %], bleeding [OR: 1.43 (0.40, 5.13); P = 0.59, I 2: 0 %], and obstruction [OR: 1.66 (0.60, 4.60); P = 0.33, I 2: 0 %]. CONCLUSION: Traditional self-expanding standard esophageal stent and anti-reflux stent with valve are similar in terms of outcomes and complications.

Incidental liver metastasis in pancreatic adenocarcinoma.

Exocrine cancer of pancreas is the fourth leading cause of death in the USA among both men and women. Contrast enhanced multidetector-row computer tomography (MDCT) is the current modality of choice for the detection of distant metastasis in pancreatic cancer as a part of pre-operative workup, which helps decide on resectability. Authors present a first ever reported case of an incidental liver metastasis found on intra-operative wedge hepatic biopsy during Whipple's procedure for pancreatic cancer. This pancreatic cancer was initially thought to be resectable based on MDCT staging per guidelines. The case highlights the importance of diagnostic staging laparoscopy and neoadjuvant chemotherapy before resecting pancreatic adenocarcinoma.

3D Printing for Bio-Synthetic Biliary Stents.

Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). RESULTS: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. CONCLUSION: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

Biomarkers of rejection in kidney transplantation.

PURPOSE OF REVIEW: To provide an update of the literature on the use of new biomarkers of rejection in kidney transplant recipients. RECENT FINDINGS: The kidney allograft biopsy is currently considered the gold standard for the diagnosis of rejection. However, the kidney biopsy is invasive and could be indeterminate. A significant progress has been made in discovery of new biomarkers of rejection, and some of them have been introduced recently for potential use in clinical practice including measurement of serum donor-derived cell free DNA, allo-specific CD154 + T-cytotoxic memory cells, and gene-expression 'signatures'. The literature supports that these biomarkers provide fair and reliable diagnostic accuracy and may be helpful in clinical decision-making when the kidney biopsy is contraindicated or is inconclusive. SUMMARY: The new biomarkers provide a promising approach to detect acute rejections in a noninvasive way.

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone.

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40 mL/min/1.73 m2 for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD-6 e-GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m2 , P=.002), higher 24-hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA, the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre-LTA e-GFR (P≤.005 at all time points). One patient developed end-stage renal disease 9 years post-LTA and another patient expired 7 years post-LTA. The low e-GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.

Drug resistance in intestinal tuberculosis: A reason to worry?

BACKGROUND AND AIM: Emergence of drug resistance in intestinal tuberculosis (ITB) makes the treatment of this condition challenging. While there is growing evidence of multiple and extensive drug resistance in pulmonary and glandular tuberculosis (TB), literature regarding susceptibility and resistance patterns in ITB is scarce. The aim of the current paper was to study the prevalence of drug resistance in patients with ITB. METHODS: Among patients presenting to a tertiary care hospital in Mumbai between 2008 and 2016, records of all patients with ITB, whose mucosal biopsy (obtained at ileocolonoscopy) tissue culture was positive for Mycobacterium tuberculosis and in whom drug sensitivity testing was performed, were retrospectively analyzed. Sensitivity and resistance to single or multiple anti-TB drugs were noted. RESULTS: A total of 43 patients were included, of whom 10 (23.2%) patients were diagnosed to have resistance to at least one first-line anti-TB drug. Resistance to isoniazid was the most common (nine patients), followed by rifampicin (six), pyrazinamide (five), streptomycin and ethionamide (four each), ethambutol, moxifloxacin and ofloxacin (three each), and p-amino salicylic acid (one). Six patients (13.9%) had multidrug-resistant TB and needed second-line anti-TB therapy as per drug sensitivity pattern. There was no patient with extensive drug-resistant TB. CONCLUSION: Twenty-three percent of our patients with ITB tested for drug resistance had drug resistance, 13.9% being multidrug resistant and needing second-line anti-TB therapy.