Presence Of Cirrhosis Research Articles

Treatment-related toxicity and improved outcomes with immune checkpoint inhibitors in patients with hepatocellular carcinoma.

4085 Background: The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI), however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). This retrospective multi-center study aimed to examine whether trAEs are prognostic in HCC. Methods: We established an international consortium of 10 tertiary-care referral centers located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to test whether the development of clinically significant trAE (i.e. graded >2, trAE2) predicted for improved overall (OS), progression-free survival (PFS), and overall response rates (ORR) following ICI, and subsequently validated this association in a separate cohort of 406 HCC patients receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. Results: In a multi-institutional cohort of 357 patients, 274 (77%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 304, 85%), trAE were reported in 146 patients (41%). Development of trAE2 were associated with longer OS (23.3 versus 12.2 months) and PFS (8.6 months versus 3.7 months). After adjusting for viral aetiology, gender, presence of cirrhosis, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy, trAE2 were confirmed predictors of improved OS (HR 0.55; 95%CI:0.34-0.88) and PFS (HR 0.51; 95%CI: 0.35-0.74). TrAE2 were associated with higher ORR (27% versus 16%) from ICI. The association between trAE2 and patients’ OS (HR 0.49; 95%CI:0.34-0.70) and PFS (HR 0.43; 95%CI:0.32-0.59) was also observed in the FDA dataset. After a 6-weeks landmark selection, trAE2 were confirmed to be associated with improved PFS (HR 0.59; 95%CI:0.39-0.87); the additional analysis adjusted for tumour response and duration of treatment within the FDA cohort further confirmed the association with longer PFS (HR 0.67; 95%CI: 0.47-0.94). Conclusions: Development of trAE2 may correlate with response and survival in patients with HCC receiving ICI, a clinical setting where the lack of biomarkers still represents an unmet need. Prospective studies aimed at understanding the underlying immunologic foundations of such relationship are warranted to identify predictive biomarkers of toxicity and response.

A nurse practitioner model of care in the era of direct acting antiviral therapy for hepatitis C virus infection.

Background and AimDirect‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has resulted in high rates of successful disease cure; however, not enough healthcare providers are available to deliver treatment to the population living with chronic HCV. To demonstrate that a nurse practitioner (NP) model of care is non‐inferior to specialist gastroenterologist (SG) management of HCV infection, as measured by sustained viral response at 12 weeks (SVR12) after initiation of DAA therapy.DesignRetrospective cohort database study.SettingSingle‐center outpatient study, Central Coast Local Health District (CCLHD).ParticipantsAll patients with chronic HCV treated in the CCLHD Liver Clinic in the period 3rd March 2016 to 31st May 2019 were retrospectively analyzed. In this time period, a total of 1638 patients with chronic HCV had completed treatment. Seven hundred and thirty‐four patients were excluded (733 pre‐PBS listing for DAAs and 1 not treated with DAA). Nine hundred and four patients were eligible for the study, of which 541 were managed by an SG, and 363 managed by an NP.Main outcome measuresData were collected on patient demographics, genotype, fibrosis score, and presence of cirrhosis. Primary end point was number of patients achieving SVR12.ResultsOf the 904 patients treated with DAA, 764 (84.5%) achieved SVR12. There was no statistical difference (P > 0.05) in achieving SVR12 between patients treated by an SP (n = 481, 88.9%) and those treated by an NP (n = 281, 77.4%).ConclusionAn NP model of care is non‐inferior to SG management of HCV infection, as evidenced by equivocal success in achieving SVR12 between the two treatment groups. Therefore, an NP model of care is a viable option in the era of DAA therapy for HCV infection. Ongoing investment into the delivery of NP care could increase treatment uptake of HCV, with the aim of decreasing overall burden of disease.

Direct-acting Antiviral Regimens for Patients with Chronic Infection of Hepatitis C Virus Genotype 3 in China

Hepatitis C virus (HCV) genotype (GT)3 infection is associated with a more rapid hepatic disease progression than the other genotypes. Hence, early HCV clearance slows down the disease progression and is important for improving prognosis in GT3-infected patients. Nevertheless, compared with other genotypes, GT3 is difficult-to-treat with direct-acting antivirals, especially in the presence of cirrhosis. Current guidelines recommend several regimens which have been proven to be effective in GT3-infected patients from the Western world (North America, Europe, and Oceania). In China, GT3 infection comprises 8.7–11.7% of the 10 million patients infected with HCV and has strikingly different characteristics from that in Western countries. Unlike the Western countries, where GT3a is the predominant subtype, GT3a and 3b each affect roughly half of Chinese GT3-infected patients, with 94–96% of the GT3b-infected patients carrying A30K+L31M double NS5A resistance-associated substitutions. Phase 3 clinical trials including GT3b-infected patients have suggested that GT3b infection is difficult to cure, making the regimen choice for GT3b-infected patients an urgent clinical gap to be filled. This review includes discussions on the epidemiology of HCV GT3 in China, recommendations from guidelines, and clinical data from both Western countries and China. The aim is to provide knowledge that will elucidate the challenges in treating Chinese GT3-infected patients and propose potential solutions and future research directions.

Hepatitis C Treatment by Directly Acting Antiviral Agents and Its Impact on Glycemic Control

Objective: To evaluate Hepatitis C treatment by directly acting antiviral agents and its impact on glycemic control. 
 Study Design: This is an observational study.
 Setting: This study was conducted in Medicine department Civil Hospital Karachi from March 2018 to December 2019.
 Materials and Methods: Patients visiting the outpatient department of the hospital having documented HCV infection having type 2 diabetes mellitus were included in the study. All participants were given directly acting antiviral treatment for 12 weeks. After treatment they were assessed for achievement of sustained virological response (SVR). Pre-treatment and post treatment fasting blood glucose levels and HbA1c levels were checked. SVR is defined as serum HCV RNA which is undetectable (<50IU/ml) after 12 weeks of antiviral treatment.
 Results: Around 332 patients matched our inclusion criteria. Amongst these there were 219 males and 113 females. The mean age of patients was 39.44 ± 2.19 years. All the selected participants started therapy on Sofosbuvir-velpatasvir (pangenotypic NS5A-NS5B inhibitor single-pill combination regimen that has potent activity against hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, and 6.) plus ribavirin. After treatment with directly acting antiviral therapy 231 (69.57%) patients achieved sustained virological response. Patients who achieved SVR showed improved glycaemic control than those who didn’t. Patients with cirrhosis showed decreased chances of attainment of SVR. Fasting blood glucose levels and HbA1c were also decreased, decreasing the amount of insulin required for diabetes control. 
 Conclusion: Our study showed that treatment with directly acting antiviral treatment improved glycaemic control in HCV infected patients. Other factors like BMI, presence of cirrhosis, mean serum HCV RNA levels and adherence to treatment were major predictors for achievement of SVR.

Persistent liver inflammation in chronic hepatitis C patients with advanced fibrosis after direct-acting antivirals induced sustained virological response.

Direct-acting antivirals (DAA) improve sustained virological response (SVR) rates with normalization of liver enzymes in patients with hepatitis C. However, liver inflammation may persist despite virus eradication. We aimed to investigate the rate and risk factors for persistent elevated aminotransferase levels in patients with advanced fibrosis after DAA-induced SVR. From January 2017 to April 2018, chronic hepatitis C patients with advanced fibrosis and SVR after DAA treatment at the Taipei Veterans General Hospital were prospectively enrolled. Persistent liver inflammation after SVR was defined as an increase in levels of alanine aminotransferase (ALT) (>40 U/L) at SVR12. A total of 461 patients were included (57.9% females, mean age 64 years, 69.6% genotype 1b, 46.4% cirrhosis). At SVR12, there was a decline in ALT levels (90.5 ± 80.8 U/L to 25.3 ± 26.5 U/L) from baseline levels. Persistent liver inflammation at SVR12 was detected in 45 patients (9.8%). The presence of cirrhosis, markers of impaired liver functions, history of interferon-based therapy, steatosis, and elevated ALT levels at baseline was associated with persistent liver inflammation after SVR12. Results of multivariate analysis indicated that levels of baseline serum total bilirubin (odds ratio [OR]: 2.605, 95% CI: 1.158-5.858), international normalized ratio (OR: 14.389, 95% CI: 1.754-118.049), ALT (OR: 1.006, 95% CI: 1.003-1.009), and the presence of steatosis (OR: 3.635, 95% CI: 1.716-7.698) were independent predictors of persistent liver inflammation at SVR12. Persistent liver inflammation is not uncommon in chronic hepatitis C patients with advanced fibrosis after DAA-induced SVR. It is associated with impaired baseline liver function and steatosis. Long-term follow-up is required to assess the implication of liver inflammation on disease progression.

DEMOGRAPHICS AND CORRELATION OF RISK FACTORS FOR HEPATOCELLULAR CARCINOMA IN PATIENTS PRESENTING TO A TERTIARY CARE FACILITY IN PAKISTAN

Objective: Demographics of HCC in Pakistan. Correlation of HCC with its possible etiology. Correlation of tumoraggressiveness with PCR status and anti-viral treatment.
 Study Design: Cross sectional study.
 Place and Duration of Study: Pak Emirates Military Hospital, Rawalpindi from Jul 2017 to Jun 2018.
 Methodology: Patients with age >18 years presenting with space occupying lesion(s) of liver were confirmed to be HCC according to standard guidelines. The variables such as age, gender, presence of cirrhosis, etiology of cirrhosis, tumor staging, viral status through PCR study and the treatment offered were documented. Baseline descriptive data was reported as mean with SD for continuous variables. Chi square test was used to compare qualitative data.
 Results: A total of 195 patients were enrolled for one year. Male population with HCC was in predominance (75.9%). Sixty one percent of the afflicted population was having liver cirrhosis, 34.9% had decompensated cirrhosis and 3.8% had no cirrhosis. HCV accounted for the bulk of patients with cirrhosis (82%) followed by HBV (9.2%), HBV and HCV co-infection (3.1%), NASH and cryptogenic cirrhosis (1.5% each). Majority got diagnosed with triphasic CECT scan Abdomen, only 3.6% needed liver biopsy for diagnosis. Majority (43.6%) belonged to BCLC B. Viral PCR was positive for 58.5% and 73.8% of the patients were treatment naïve.
 Conclusion: HCC shows highest rates seen in male patients presenting in old age. Gender, classes of cirrhosis, number of lesions, portal vein thrombosis and extrahepatic metastasis correlated with possible risk factors of HCC. Tumor aggressiveness correlated with PCR status..............

Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients.

Potent antiviral agents effectively reduce liver-related events in patients with chronic hepatitis B. This study aimed to determine whether alanine aminotransferase normalization using potent antiviral agents was related to hepatocellular carcinoma development. From 2007 to 2017, we included 610 patients with chronic hepatitis B who received entecavir or tenofovir disoproxil fumarate. The patients were divided into the alanine aminotransferase normalization group (Gr.1) and non-normalization group (Gr.2) within a year of potent antiviral treatment. Liver-related events included hepatic encephalopathy, variceal bleeding, and ascites. The mortality rate and hepatocellular carcinoma incidence were investigated for each group. The patients who showed ALT normalization at 1 year of treatment were 397 (65.1%) of 610. During a median follow-up period of 86 months, 65 (10.7%) patients developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma was significantly lower in Gr.1 than in Gr.2 (p < 0.001). Risk factors for alanine aminotransferase non-normalization were body mass index, cholesterol, and liver cirrhosis at baseline. Male sex, age, platelet level, alcohol use, presence of cirrhosis at baseline, and non-normalization after 1 year of treatment were independent risk factors for hepatocellular carcinoma. Alanine aminotransferase normalization within 1 year of initiating antiviral agents reduces the risk of hepatocellular carcinoma development.

Treatment of viral hepatitis C genotypes 1 and 2 by sofosbuvir and ledipasvir with or without ribavirin combination: A possible alternative to pangenotypic treatment in a low-income country?

ObjectivesThe aim of this study was to evaluate the efficacy and safety of sofosbuvir/ledipasvir ± ribavirin in Malagasy patients with hepatitis C virus genotypes 1 and 2, in real conditions. Patients and methodsThis was a retrospective monocentric clinical study, carried out over a period of 3 years from March 1, 2017 to February 28, 2020, in a hospital hepato-gastroenterology department. ResultsIn total, 26 patients (M/F: 11/15) with hepatitis C virus genotype 1 (n = 13) or genotype 2 (n = 13), were treated with sofosbuvir/ledipasvir without (n = 21) or with (n = 5) ribavirin for 12 weeks. The mean age was 61.38 ± 7.09 years. Seventeen patients (65.4%) had cirrhosis. The overall sustained virological response was 96.2% (95% CI = 80.4–99.9%). There was no significant difference between the sustained virological responses of genotypes 1 and 2 (92.3% vs 100%; p = 0.31) or those of cirrhotic or non-cirrhotic patients (94.1% vs 100%; p = 0.46). A relapse was observed in one patient (5.9%) — cirrhotic and genotype 1b — under sofosbuvir/ledipasvir with ribavirin. Seven patients (26.9%) experienced mild adverse reactions, including asthenia (57.1%) and insomnia (42.9%). ConclusionTreatment with sofosbuvir/ledipasvir ± ribavirin for infection with hepatitis C virus genotype 1 has been shown to be safe and effective, even in the presence of cirrhosis. The sofosbuvir/ledipasvir combination is a good option for genotype 2 non-cirrhotic patients.

Endogenous Opioid Levels Do Not Correlate With Itch Intensity and Therapeutic Interventions in Hepatic Pruritus.

Background: Chronic pruritus affects up to 70% of patients with immune-mediated hepatobiliary disorders. Antagonists of the μ-opioid receptor (MOR) and agonists of the κ-opioid receptor (KOR) are used to treat hepatic itch, albeit with limited success. An imbalance between ligands of MOR and KOR receptors has recently been suggested as a potential mechanism of hepatic pruritus. In this study, we therefore investigated systemic levels of important endogenous opioids such as β-endorphin, dynorphin A, Leu- and Met-enkephalin in plasma of a large cohort of well-characterized patients with immune-mediated cholestatic disorders, including patients with liver cirrhosis, and during effective anti-pruritic therapy.Methods: Plasma samples and clinical data were prospectively collected from well-characterized patients with primary/secondary sclerosing cholangitis (PSC/SSC), primary biliary cholangitis (PBC) and overlap syndromes suffering from pruritus (n = 29) and age-, gender- and disease-matched controls without pruritus (n = 27) as well as healthy controls (n = 20). General laboratory testing for hepatobiliary and renal function was performed. Levels of β-endorphin, dynorphin A, Leu- and Met-enkephalin were quantified in plasma by ELISA. Intensity of pruritus over the last week was evaluated using a visual analog scale (VAS, 0–10).Results: PBC and PSC patients with or without pruritus did neither differ in disease entity, disease stage, nor in the presence of cirrhosis. While both dynorphin A and β-endorphin concentrations were lower in pruritic patients compared to those without pruritus and healthy controls, the MOR/KOR ligand ratio was unaltered. No significant differences were observed for Leu- and Met-enkephalin concentrations. Opioid levels correlated with neither itch intensity nor stage of disease. Cirrhotic patients displayed higher concentrations of MOR agonist Leu-enkephalin and KOR agonist dynorphin A. Endogenous opioid levels remained largely unchanged after successful treatment with the potent anti-pruritic drugs rifampicin and bezafibrate.Conclusions: Endogenous opioid levels and the MOR/KOR ligand ratio neither correlate with itch intensity nor differentiate pruritic from non-pruritic patients with immune-mediated liver diseases. Thus, endogenous opioids may modulate signaling pathways involved in hepatic pruritus, but are unlikely to represent the major pruritogens in liver disease.

Clinical and Pathological Attributes of Hepatocellular Carcinoma Showing Lack of Restricted Diffusion on Magnetic Resonance Imaging

Objective: To correlate non-restricted diffusion magnetic resonance imaging (MRI) patterns of hepatocellular carcinoma (HCC), with histopathology and clinical outcome.Material and Methods: We retrospectively evaluated pre-treatment MRIs showing non-restricted diffusion HCC lesions (≥1-centimeter), excluding lesions with poor quality/non-available diffusion weighted imaging (DWI). Three radiologists evaluated 37 lesions in 27 patients, for: T1-weighted (T1W)/T2-weighted (T2W) characteristics, arterial enhancement, washout on portal venous/delayed phase, capsular enhancement, intralesional fat component and presence of cirrhosis. Histopathological reports were categorized as: well/moderate/poorly differentiated. Kaplan-Meier survival analysis was calculated for clinical outcome.Results: From a total of 37 lesions, 24 lesions had available pathological grading, which revealed well and moderately differentiated equally (12 lesions each). None of the non-restricted diffusion HCCs were poorly differentiated. Thirty-five of the 37 lesions (94.6%) showed arterial enhancement with washout; 34 lesions (91.9%) were T2W hypo-/isointense, 33 esions (89.2%) were T1W iso-/hyperintense, 19 lesions (51.4%) showed capsular enhancement and 8 lesions (21.6%) had intralesional fat. These findings in the well and moderately differentiated groups were not significantly different (p-value 0.178-1.000). Overall mean-survival was 6.972 years (95% confidence interval (CI); 5.3-8.6). The 1-year, overall survival rate was 83.6% and for 3-years was 67.9%. Mean survival of well and moderately differentiated groups were 6.88 and 7.23 years (95% CI 5.7-8.0 and 4.4-10.1), respectively (p-value=0.319).Conclusion: DWI may help to predict histological grading of HCC and clinical outcome. We found that non-restricted diffusion HCCs were histologically well or moderately differentiated, with no significant difference of imaging findings and survival rates between the two groups. No poorly differentiated lesions were seen in our non-restricted HCC cohort.

Sofosbuvir and Velpatasvir combination is safe and effective in treating chronic hepatitis C in end-stage renal disease on maintenance haemodialysis.

There is emerging data on the use of Sofosbuvir-based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with end-stage renal disease (ESRD) on maintenance haemodialysis (MHD). We evaluated the safety and efficacy of Sofosbuvir plus Velpatasvir fixed-dose combination in CHC patients with ESRD on MHD. Fifty-one CHC patients with ESRD on MHD were included in a real-life prospective study. All patients irrespective of genotype; presence of cirrhosis; treatment naive or experienced status were treated with full-dose Sofosbuvir (400mg) plus Velpatasvir (100mg) fixed-dosed combination given daily for 12weeks. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12weeks after the end of treatment (ETR). Side effects if any were recorded in all patients. The median HCV RNA level in 51 CHC patients [Males 41 (80.4%), mean age 42.8±14.6years] was 2.0×106 IU/mL. HCV genotype was available in 19 patients with predominant genotype 1 in 15 (79%) patients. Ten (19.6%) patients had evidence of cirrhosis (defined as LSM≥12.5kPa on Transient Elastography), and 8 (15.6%) patients were treatment experienced. Testing for ETR was done in 36 patients and all 36 (100%) patients achieved ETR, and 49 patients (96%) achieved SVR 12. All 51 patients tolerated the Sofosbuvir+Velpatasvir combination, with none of the patients reporting any serious adverse event. Sofosbuvir plus Velpatasvir fixed-dose combination is safe and effective in treating CHC in patients with ESRD on MHD.

Twelve-month post-treatment parameters are superior in predicting hepatocellular carcinoma in patients with chronic hepatitis B.

There are currently several prediction models for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) receiving oral antiviral therapy. However, most models are based on pre-treatment clinical parameters. The current study aimed to develop a novel and practical prediction model for HCC by using both pre- and post-treatment parameters in this population. We included two treatment-naïve CHB cohorts who were initiated on oral antiviral therapies: the derivation cohort (n=1480, Korea prospective SAINT cohort) and the validation cohort (n=426, the US retrospective Stanford Bay cohort). We employed logistic regression, decision tree, lasso regression, support vector machine and random forest algorithms to develop the HCC prediction model and selected the most optimal method. We evaluated both pre-treatment and the 12-month clinical parameters on-treatment and found the 12-month on-treatment values to have superior HCC prediction performance. The lasso logistic regression algorithm using the presence of cirrhosis at baseline and alpha-foetoprotein and platelet at 12months showed the best performance (AUROC=0.843 in the derivation cohort. The model performed well in the external validation cohort (AUROC=0.844) and better than other existing prediction models including the APA, PAGE-B and GAG models (AUROC=0.769 to 0.818). We provided a simple-to-use HCC prediction model based on presence of cirrhosis at baseline and two objective laboratory markers (AFP and platelets) measured 12months after antiviral initiation. The model is highly accurate with excellent validation in an external cohort from a different country (AUROC 0.844) (Clinical trial number: KCT0003487).

Salvage Therapy with Sofosbuvir/Velpatasvir/Voxilaprevir in DAA-experienced Patients: Results from a Prospective Canadian Registry.

Despite the current highly effective therapies with direct-acting antiviral agents (DAAs), some patients with chronic hepatitis C virus (HCV) infection still do not achieve sustained virological response (SVR) and require retreatment. Sofosbuvir/velpatasvir/voxilaprevir (SVV) is recommended as the first-line retreatment option for most patients. The aim of this study was to evaluate the efficacy of SVV as salvage therapy after at least one course of DAA. Data were collected on all HCV-infected patients who failed DAAs and were prescribed SVV from a prospective Canadian registry (CANUHC) including 17 sites across Canada. Factors associated with failure to achieve SVR with SVV therapy and the utility of RAS testing and ribavirin use were evaluated. A total of 128 patients received SVV after non-SVR with DAA treatment: 80% male, median age 57.5 (31-86), 44% cirrhotic, and 17 patients post liver transplant. First line regimens included: sofosbuvir/velpatasvir (27.3%), sofosbuvir/ledipasvir (26.5%), grazoprevir/elbasvir (12.5%), other (33.5%). Ribavirin was added to SVV in 26 patients due to past sofosbuvir/velpatasvir use (n = 8), complex resistance associated substitution profiles (n = 16) and/or cirrhosis (n = 9). Overall SVR rate was 96% (123/128). Of 35 patients who previously failed sofosbuvir/velpatasvir, 31 (88.5%) achieved SVR compared to 92 of 93 (99%) among those receiving any other regimen (P = .01). Similar to reports from phase 3 clinical trials, SVV proved highly effective as salvage therapy for patients who failed a previous DAA therapy. Those who failed SVV had at least 2 of the following factors: genotype 3, presence of cirrhosis, past liver transplantation, past exposure to sofosbuvir/velpatasvir and/or complex resistance profiles.

Coagulation balance and liver damage in non-cirrhotic patients with chronic hepatitis C after eradication by Direct-acting Antiviral Agents (DAAs)

Introduction: Chronic HCV infection causes liver damage of different severity. A procoagulant imbalance has been reported in patients with chronic hepatitis C (CHC) mainly in presence of cirrhosis.

Impact of direct-acting antiviral regimens on mortality and morbidity outcomes in patients with chronic hepatitis c: Systematic review and meta-analysis.

The long-term effects of direct-acting antiviral therapies (DAAs) for chronic hepatitis C (CHC) remain uncertain. The objective of this systematic review and meta-analysis was to assess the impact of DAAs on CHC progression and mortality. We searched Ovid MEDLINE, Ovid EMBASE and PubMed databases (January 2011 to March 2020) for studies that compared the efficacy of DAAs to a non-DAA control in patients with CHC. Main outcomes were the adjusted hazard ratios (HRs) for mortality, liver decompensation, HCC occurrence and recurrence. Pooled estimates of HRs were determined using random-effects meta-analyses with inverse variance weighting, with sensitivity analyses and meta-regression to explore the effects of clinical factors. We identified 39 articles for the primary analysis. Compared with unexposed individuals, patients treated with DAA had a reduced risk of death (HR; CI=0.44; 0.38-0.52), decompensation (HR; CI=0.54; 0.38- 0.76) and HCC occurrence (HR; CI=0.72; 0.61- 0.86). The protective effect of DAA on HCC recurrence was less clear (HR; CI=0.72; 0.44-1.16). Sustained virologic response (SVR) attainment was a significant predictor of reduced mortality (HR; CI=0.33; 0.23-0.46), decompensation (HR; CI=0.11; 0.05-0.24), HCC occurrence (HR; CI=0.31; 0.27-0.37) and HCC recurrence (HR; CI=0.32; 0.20-0.51). Meta-regression showed no evidence of effect modification by patient age, sex, presence of cirrhosis or length of follow-up. In conclusion, our findings show protective effects of DAA treatment and DAA-related SVR on CHC progression and mortality.

Thrombin Is an Effective and Safe Therapy in the Management of Bleeding Gastric Varices. A Real-World Experience.

Variceal haemorrhage is a severe complication of liver disease with high mortality. Human recombinant thrombin has gained popularity in the management of variceal haemorrhage. We report on the use of thrombin for gastric and ectopic varices at a regional tertiary care centre. This was a retrospective observational study. Patients with portal hypertension who received endoscopic injection of recombinant thrombin were identified and data collected on haemostasis and rebleeding rates, complications and mortality. Patients were grouped by indication for thrombin injection: gastric/oesophageal/ectopic varices and endoscopic band ligation (EBL)-induced ulceration. 155 patients (96M/59F, mean age 58.3 years) received endoscopic thrombin injection. Mean volume of thrombin injected at index endoscopy was 9.5 ml/2375IU. Initial haemostasis was achieved in 144 patients (92.9%). Rebleeding occurred in a total of 53 patients (36.8%) divided as follows: early rebleeding (<5 days from index endoscopy)—26 patients (18%); rebleeding within 30 days—42 patients (29.1%); delayed rebleeding (> 30 days)—11 patients (7.6%). There was statistically significant difference in rate of initial haemostasis between Child-Pugh A/B patients vs Child-Pugh C (p = 0.046). There was no significant difference in rebleeding rates between different indication groups (p = 0.78), by presence of cirrhosis or by Child-Pugh Score. All-cause mortality at 6 weeks was 18.7%; 1-year mortality 37.4% (median follow-up 48 months). There was no significant difference in mortality between groups (p = 0.37). No significant adverse events or complications were reported. Thrombin is effective and safe for gastric varices and other portal-hypertension-related bleeding including oesophageal varices, ulcers secondary to EBL and ectopic varices.

"If I Get Cured, My Whole Quality of Life Will Change": Patients' Anticipated and Actualized Benefits Following Cure from Chronic Hepatitis C.

Patients' motivations for undergoing direct-acting antiviral (DAA) therapy for chronic hepatitis C may include anticipation of treatment benefits not well described in the literature. Evaluate patients' anticipated and actualized improvements in several domains of functioning before and after viral cure. Pre-post-study utilizing in-depth interviews with 28 patients prior to, and several months after, DAA therapy. Interviews were audio-recorded, transcribed, coded, and analyzed by two qualitative experts. Patients had a median age of 54years, 43% were male, 57% white, 25% had cirrhosis, and 71% were treated with sofosbuvir/ledipasvir. Pre-treatment, patients hoped for improvements in several domains including psychological, emotional, physical, social, and occupational functioning. After viral cure, increased energy and less fear of transmission were pathways to better quality of life. Psychological and emotional improvements positively affected physical, social, and occupational functioning. Social improvements were due to better mood and motivation, fewer symptoms, and reduced fear of stigma and transmission. Occupational benefits were linked to increased stamina, self-confidence, and less pain, anxiety, and stigma. Reduced fear of stigma had a pervasive impact on all life improvements after cure. Patient characteristics such as the presence of cirrhosis or psychiatric issues influence treatment motivations. Qualitative data correspond with change in pre-post-survey scores. Tremendous hope is placed on the ability of DAA therapy to bring about substantial improvements in life functioning after viral cure. Highly interconnected effects on quality of life worked synergistically through improved physical and psychological well-being. Stakeholders should appreciate the multi-dimensional benefits that viral eradication bestows upon individuals and society.

FREQUENCY OF HEPATOCELLULAR CARCINOMA AND ASSOCIATED SOCIODEMOGRAPHIC FACTORS IN TREATED PATIENTS OF CHRONIC HEPATITIS C

Objective: To look for frequency and associated socio-demographic factors of newly diagnosed patients of heaptocellular carcinoma (HCC) among patients treated adequately for hepatitis C infection.&#x0D; Study Design: Correlational study.&#x0D; Place and Duration of Study: Gastroenterology Department, Pak Emirates Military Hospital Rawalpindi, fromNov 2017 to Oct 2018.&#x0D; Methodology: This analysis was performed on 170 patients treated effectively for hepatitis C with standard antiviral therapy at our hospital. They were followed up for two years after the sustained viral response has been achieved. Ultrasonography was done in all cases and contrast enhanced computerized tomography scan done on patients who were positive on ultrasound. Factors like age, gender, genotype of heaptocellular carcinoma, presence of cirrhosis and model for end-stage liver disease (MELD) score were related with presence of heaptocellular carcinoma among the target population.&#x0D; Results: Out of 170 patients included in final analysis 121 were male, 49 were female. About 53 patients werediagnosed as suffering from heaptocellular carcinoma while 117 were negative for that. Thirty six patients hadcirrhosis while 134 non cirrhotic. After applying the binary logistic regression genotypes other than 3, high model for end-stage liver disease score &amp; presence of cirrhosis had a strong relationship with presence of heaptocellular carcinoma among the patients treated for hepatitis C virus.&#x0D; Conclusion: Physicians and patients cannot ignore the possibility of a malignant outcome even after successfultreatment of hepatitis C. Local protocols should be set for screening especially the high risk cases even aftertreatment of hepatitis..........

Safe standard remnant liver volume after hepatectomy in HCC patients in different stages of hepatic fibrosis

BackgroundTo determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy.MethodsData for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage.ResultsLogistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001).ConclusionsRight hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.

Characteristics and etiologies of hepatocellular carcinoma in patients without cirrhosis: When East meets West

A recent study from the United States reported that nearly 12% of hepatocellular carcinomas (HCCs) occurred in patients without cirrhosis. Non-alcoholic fatty liver disease (NAFLD) was the most common liver disease in these patients. We aim to evaluate the characteristics, etiologies, and outcomes of cases of non-cirrhotic HCC in East Asia, where there is a higher prevalence of hepatitis B virus (HBV)-associated non-cirrhotic HCC. This retrospective study consecutively enrolled de novo HCC patients managed at our institution from 2011 to 2017. The presence of cirrhosis was assessed by histology; if histology was not available, it was assessed by image study. 2055 patients with HCC were enrolled in this study. Among them, 529 (25.7%) were non-cirrhotic. The non-cirrhotic patients were younger (60.9 vs. 62.5 years, p = 0.006), included a greater proportion of males (78.1% vs. 71.3%, p = 0.002), and had a lower body mass index (24.3 vs. 25.3 kg/m2, p<0.001) than the cirrhotic patients. Among the non-cirrhotic patients, HBV was the most common liver disease (49.0%). The patients with non-cirrhotic HCC had larger tumors (5.9 vs. 4.7 cm, p<0.001), underwent liver resection at a higher rate (66.0% vs. 17.4%, p<0.001), and had better overall survival than the cirrhotic HCC patients (median 5.67 vs. 2.83 years, p<0.001). Nearly 26% of the HCCs occurred in patients without cirrhosis. HBV was the most common liver disease in these patients, and the survival was better in the non-cirrhotic patients than the cirrhotic patients.