Compensated Liver Disease Research Articles

Combining FIB-4 and Liver Stiffness Into the FIB-5, a Single Model that Accurately Predicts Complications of Portal Hypertension.

We aimed to combine the fibrosis (FIB)-4 score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease. In this retrospective cohort study, we identified 5849 US veterans who underwent LS measurement from May 01, 2014 to June 30, 2019, and laboratory tests enabling FIB-4 calculation within 6 months of LS measurement. Patients were followed up from the LS measurement date until February 05, 2020, for incident complications of PH. We combined LS values and the individual components of the FIB-4 score (i.e. age, aspartate aminotransferase, alanine aminotransferase, and platelet count) using multivariable Cox proportional hazards modeling and the machine learning algorithm eXtreme gradient boosting to develop the C-FIB-5 and X-FIB-5 models, respectively. Models were internally validated using optimism-corrected measures. Among 5,849 patients, the mean age was 62.8 years, 95.9% were men, and the mean follow-up time was 2.14 ± 1.21 years. Within 3 years after LS measurement date, 116 (2.0%) patients developed complications of PH. The X-FIB-5 (area under the receiver operating characteristic [AUROC] 0.845) and C-FIB-5 scores (AUROC 0.868) demonstrated superior discrimination over LS (AUROC 0.688) and FIB-4 (AUROC 0.672) for predicting incident complications of PH. Both the X-FIB-5 and C-FIB-5 models demonstrated higher classification accuracy across all sensitivity cutoffs when compared with LS or FIB-4 alone. We combined LS and the individual components of the FIB-4 into a single scoring system (FIB-5, www.fib5.net ), which can help identify patients with compensated liver disease at risk of developing complications of PH.

SAFETY AND EFFICACY OF DIRECT ACTING ANTIVIRALS FOR CHRONIC HEPATITIS C IN PATIENTS WITH CHRONIC KIDNEY DISEASE ON MAINTENANCE HEMODIALYSIS

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and is associated with increased morbidity and mortality. Aim of the study is to assess the safety and efficacy of pangenotypic DAA regimens in patients with chronic disease on maintenance hemodialysis. In thisMATERIALS AND METHODS: prospective observational study, hemodialysis patients with chronic hepatitis C infection were identified and treatment initiated with appropriate pangenotypic regimen. Totally 74 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indices and adverse reactions during the treatment process were also assessed. All theRESULTS: patients enrolled completed 12 weeks of treatment. 12 out of 74(16.2%) patients had compensated liver disease. SVR was achieved in 12 out of 12 patients (100%) receiving sofosbuvir/velpatasvir, and 60 of 62 patients (96.7%) receiving sofosbuvir/daclatasvir. No serious or significant adverse reactions were reported. PangenotypicCONCLUSION: regimens containing sofosbuvir are safe and well tolerated in patients with chronic kidney disease on maintenance hemodialysis. Sofosbuvir/daclatasvir based regimens at full dose can be used as an alternative pan genotypic regimen in patients with chronic kidney disease on hemodialysis.

Alcohol-related hepatocellular carcinoma is a heterogenous condition: Lessons from a latent class analysis.

BackgroundAlcohol‐associated hepatocellular carcinoma (AL‐HCC) poor prognosis has been attributed to diagnosis at a later stage. However, host factors and specific health trajectories have been associated with severe outcomes in alcohol‐related liver disease. We hypothesize AL‐HCC is not a homogeneous condition but encompasses subgroups yielding different outcomes.AimsOur aim was to provide a first attempt at a clinical phenotyping of AL‐HCC.MethodsWe analysed data for the calendar years 2007–2013 from the French nationwide administrative hospital database. We selected patients with AL‐HCC only. Clustering of AL‐HCC phenotypes was performed by latent class analysis (LCA).ResultsThe study included 11 363 patients with AL‐HCC, mainly male (89.6%), median age 67 years [IQR: 61; 74] of which 71.2% had at least one metabolic comorbidity. Five phenotypes were identified. Phenotype 1 (41.4%) displayed high rates of unrecognized cirrhosis prior to HCC diagnosis (81%), low rates of metabolic comorbidities (diabetes 13%), and mostly compensated liver disease at HCC diagnosis while the four other phenotypes displayed high rates of metabolic comorbidities (diabetes up to 100%), various patterns of liver disease trajectories and overall 42% unrecognized cirrhosis. In adjusted survival analysis, compared to phenotype 1, risk of death after HCC diagnosis was significantly different for all phenotypes.ConclusionLCA uncovers AL‐HCC is a heterogeneous condition with distinct phenotypes yielding specific survival outcomes. Frequent unrecognized cirrhosis prior to HCC underlines the urgent need for implementing strategies to identify the underlying liver disease prior to HCC onset in patients with documented alcohol use disorders and metabolic comorbidities.

Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers.

Simple SummaryHepatocellular carcinoma is one of the most common cancers in the world with increasing incidence. In advanced stages, according to the Barcelona Clinic Liver Cancer (BCLC) staging defined by number, size, vessel infiltration status, and patient’s performance status, the therapy of choice is systemic therapy. For several years, the tyrosine kinase inhibitor sorafenib was the only therapeutic option. Atezolizumab and bevacizumab are administered as a combination therapy promoting PD-L1 inhibition and anti-VEGF activity, which yields synergistic effects against cancer. The IMBRAVE150 trial investigated the use of this combination therapy versus that of sorafenib and showed an increase in overall patient survival to nearly 20 months. In this work, we investigated the real-world efficacy and safety of this combination in different centers.The combination of atezolizumab and bevacizumab (A + B) is the new standard of care for the systemic first-line treatment of hepatocellular carcinoma (HCC). However, up to now there are only few data on the safety and efficacy of A + B in real life. We included patients with advanced HCC treated with A + B as first-line therapy at four cancer centers in Germany and Austria between December 2018 and August 2021. Demographics, overall survival (OS), and adverse events were assessed until 15 September 2021. We included 66 patients. Most patients had compensated cirrhosis (n = 34; 52%), while Child–Pugh class B cirrhosis was observed in 23 patients (35%), and class C cirrhosis in 5 patients (8%). The best responses included a complete response (CR) in 7 patients (11%), a partial response (PR) in 12 patients (18%), stable disease (SD) in 22 patients (33%), and progressive disease in 11 patients (17%). The median progression-free (PFS) survival was 6.5 months, while the median overall survival (OS) was not reached in this cohort (6-month OS: 69%, 12-month OS: 60%, 18-month OS: 58%). Patients with viral hepatitis seemed to have a better prognosis than patients with HCC of non-viral etiology. The real-world PFS and OS were comparable to those of the pivotal IMBRAVE trial, despite including patients with worse liver function in this study. We conclude that A + B is also highly effective in a real-life setting, with manageable toxicity, especially in patients with compensated liver disease. In patients with compromised liver function (Child B and C), the treatment showed low efficacy and, therefore, it should be well considered before administration to these patients.

Diagnostic and prognostic significance of cell death markers in patients with cirrhosis and acute decompensation.

BackgroundThe transition from compensated to decompensated liver cirrhosis is a hallmark of disease progression, however, reliable predictors to assess the risk of decompensation in individual patients from routine diagnostics are lacking. Here, we characterize serum levels of cell death-associated markers and routine biochemistry from patients with chronic liver disease with and without decompensation.MethodsA post-hoc analysis was based on prospectively collected clinical data from 160 patients with chronic liver disease, stably compensated or decompensated at baseline or during follow-up, over a median period of 721 days. Serum levels of damage-associated molecular patterns (DAMPs) and routine biochemistry are quantified at baseline (for all patients) and during follow-up (for patients with acute decompensation). The panel of DAMPs assessed in this study comprises high-mobility group-box protein 1 (HMGB1), cytochrome C (cyt C), soluble Fas-ligand (sFasL), interleukin 6 (IL-6), soluble cytokeratin-18 (CK18-M65) and its caspase‐cleaved fragment CK18-M30.ResultsIn this cohort study, 80 patients (50%) were diagnosed with alcoholic liver cirrhosis, 60 patients (37.5%) with hepatitis C virus- and 20 patients (13.5%) with hepatitis B virus-related liver cirrhosis. At baseline, 17 patients (10.6%) showed decompensated liver disease and another 28 patients (17.5%) developed acute decompensation during follow-up (within 24 months). One hundred fifteen patients showed stable liver disease (71.9%). We found DAMPs significantly elevated in patients with decompensated liver disease versus compensated liver disease. Patients with acute decompensation during follow-up showed higher baseline levels of IL-6, sFasL, CK18-M65 and–M30 (P<0.01) compared to patients with stably compensated liver disease. In multivariate analyses, we found an independent association of baseline serum levels of sFasL (P = 0.02; OR = 2.67) and gamma-glutamyl transferase (GGT) (P<0.001; OR = 2.1) with acute decompensation. Accuracy of the marker combination for predicting acute decompensation was high (AUC = 0.79). Elevated aminotransferase levels did not correlate with decompensated liver disease and acute decompensation.ConclusionsDAMPs are elevated in patients with decompensated liver disease and patients developing acute decompensation. The prognostic value of a marker combination with soluble Fas-ligand and GGT in patients with liver cirrhosis should be further evaluated.

Viral hepatitis: Innovations and expectations.

Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and HEV) can evolve in chronic infections, whereas hepatitis A virus (HAV) frequently produces acute self-limiting hepatitis. In the last years, different studies have been performed to introduce new antiviral therapies. The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications. This review analyzes currently available therapies, in particular for viruses associated with chronic liver disease. The focus is especially on HBV and HCV therapies, investigating new drugs already introduced in clinical practice and clinical trials. We also describe new entry inhibitors, developed for the treatment of chronic HDV and HBV and currently available treatments for HEV. The last drugs introduced have shown important efficacy in HCV, with achievable target HCV elimination by 2030. Concurrently, renewed interest in curative HBV therapies has been registered; current nucleotide/nucleoside analogs positively impact liver-related complications, ensuring high safety and tolerability. Novel approaches to HBV cure are based on new antivirals, targeting different steps of the HBV life cycle and immune modulators. The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents, as bulevirtide, the first drug conditionally approved in Europe for HDV associated compensated liver disease. Further studies are required to identify a new therapeutic approach in hepatitis E, especially in immunosuppressed patients.

Safety and efficacy of daclatasvir with sofosbuvir and ribavirin in hepatitis C virus infection: A real world experience from South Punjab, Pakistan.

Objectives: This study aimed to evaluate the efficacy and safety of SOF/DCV/RBV combination to treat CHC patients at a tertiary care hospital in South Punjab. Study Design: Prospective Study. Setting: Nishtar Medical University Multan. Period: October 2019 to August 2020. Material &amp; Methods: Patients of CHC of any genotype were enrolled prospectively. They were treated with 12 weeks course of SOF/DCV/RBV combination. Effectiveness was evaluated by end of treatment response (ETR) and sustained virological response (SVR) at 12 and 24 weeks post-treatment. Adverse events were recorded for safety analysis. Results: We analyzed data of 102 patients of CHC (40 males and 62 females). The mean age was 40.04 + 10.22 years. Mean weight was 67.24 + 11.78 kg, while mean body mass index (BMI) was 26.32 + 4.58 kg/m2. Eighty patients belonged to low socio-economic status, while 22 belonged to middle socio-economic status. Sixty-four had a rural background, while 38 were from urban background. Seventy-four patients had no co-morbid condition; 16 (15.7%) had diabetes and 12 (11.8%) patients had co-morbid hypertension. Ninety percent of the patients did not have cirrhosis; 6% had compensated liver disease, while 4 % had decompensated liver disease. All the patients achieved undetectable HCV RNA at the end of treatment and 12 weeks after completion of treatment, while SVR at 24 weeks was achieved in 98% of patients. Only 2 patients discontinued treatment as a result of side effects. The most common side effects reported include fatigue, headache and fever. Conclusion: CHC is a grave problem in developing countries like Pakistan. The SOF/DCV/RBV combination is very effective in eradicating CHC and has a very good side effect profile as well.

Risk factors associated with non-malignant portal vein thrombosis in patients with decompensated cirrhosis : a case-control study

Backgrounds and Aim: Portal vein thrombosis (PVT) is defined as thrombosis of the portal vein and branches of spleno-portal axis. Incidence of PVT in compensated liver disease is between 0.6-5% and up to 25% in advanced disease. Presence of PVT in decompensated chronic liver disease (DCLD) is associated with significant morbidity and mortality. We evaluated the proportion and risk factors associated with non-malignant PVT in DCLD patients. Methods: 502 patients with DCLD were enrolled over a period of 1.5 years. Patients underwent detailed clinical history and evaluation, baseline investigation and ultrasonography. CECT Abdomen was performed in patients with USG evidence of PVT or alteration in portal flow dynamics. Results: 39 patients were excluded. 51 of the 463 patients included had PVT (11.0%). Duration of cirrhosis >4years(p<0.01), NASH related etiology (p<0.01), prior history of obesity(p<0.01), dyslipidaemia with high serum cholesterol and LDL(p<0.01), clinically evident sarcopenia (p<0.01), first initial decompensation of cirrhosis as upper gastro-intestinal bleed (UGIB), prior UGIB (p=0.002), poorly controlled ascites (p<0.01), 2 history of episodes of SBP(p<0.01), platelet count <66.5x109/L(p=0.002), leucocyte count <5350/cu mm(p<0.01) were significantly associated with PVT group. There was no difference between CHILD B and C status, among the 2 groups. On multiple logistic regression analysis, prior endoscopic variceal ligation, SAAG >1.95 were found as independent risk factors for development of PVT in DCLD patients. Conclusions: Proportion of non-malignant PVT in decompensated cirrhosis was 11%. Presence of poorly controlled ascites, prior history of UGIB, high SAAG, low Platelet count as markers of severity of portal hypertension in cirrhosis are significantly associated with non-malignant PVT in DCLD. Patients with prior history of obesity and dyslipdemia, with NASH related cirrhosis are at high risk for PVT development.

Diagnostic Tests: Testing for cirrhosis

SUMMARYCirrhosis can be suspected by a thorough clinical assessment, but compensated liver disease is often asymptomatic. Select investigations are therefore critical for identifying patients with advanced liver disease and cirrhosisBiomarkers and validated serum tests can evaluate liver damage and synthetic function. The ratio of the concentration of aspartate aminotransferase to the platelet count can predict the presence of cirrhosisNon-invasive imaging techniques, from basic ultrasound to elastography, are critical adjuncts to the clinical assessment of cirrhosis. They reduce the need for liver biopsyCareful monitoring, prescribing and appropriate specialist referral are key considerations in cirrhosis management. Early diagnosis can help to improve the outcomes for patients

National Trends and Waitlist Outcomes of Locoregional Therapy Among Liver Transplant Candidates With Hepatocellular Carcinoma in the United States

Policy changes in the United States have lengthened overall waiting times for patients with hepatocellular carcinoma (HCC). We investigated temporal trends in utilization of locoregional therapy (LRT) and associated waitlist outcomes among liver transplant (LT) candidates in the United States. Data for primary adult LT candidates listed from 2003 to 2018 who received HCC exception were extracted from the Organ Procurement and Transplantation Network database. Explant histology was examined, and multivariable competing risk analysis was used to evaluate the association between LRT type and waitlist dropout. There were 31,609 eligible patients with at least 1 approved HCC exception, and 34,610 treatments among 24,145 LT candidates. The proportion with at least 1 LRT recorded increased from 42.3% in 2003 to 92.4% in 2018. Chemoembolization remains the most frequent type, followed by thermal ablation, with a notable increase in radioembolization from 3% in 2013 to 19% in 2018. An increased incidence of LRT was observed among patients with tumor burden beyond Milan criteria, higher α-fetoprotein level, and more compensated liver disease. Receipt of any type of LRT was associated with a lower risk of waitlist dropout; there was no significant difference by number of LRTs. In inverse probability of treatment weighting-adjusted analysis, radioembolization or ablation as the first LRT was associated with a reduced risk of waitlist dropout compared with chemoembolization. In a large nationwide cohort of LT candidates with HCC, LRT, and in particular radioembolization, increasingly was used to bridge to LT. Patients with greater tumor burden and those with more compensated liver disease received more treatments while awaiting LT. Bridging LRT was associated with a lower risk of waitlist dropout.

Bulevirtide in chronic hepatitis D: a profile of its use

Bulevirtide (HEPCLUDEX®), a first-in-class entry inhibitor, is a new option for the treatment of chronic hepatitis D, caused by hepatitis delta virus (HDV) infection, in HDV-RNA positive adults with compensated liver disease. In a pivotal phase IIb trial in patients with chronic hepatitis D, treatment with bulevirtide in combination with tenofovir significantly reduced HDV RNA levels compared with treatment of the underlying HBV infection with tenofovir alone. Alanine aminotransferase (ALT) levels were also normalised by bulevirtide combination therapy. Bulevirtide is generally well tolerated; the most common adverse event in clinical trials was dose-dependent and asymptomatic increase in bile salts (reversible upon treatment discontinuation).

Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life.

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex® ) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real-life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2mg/d in subcutaneous injection) and pegylated interferon (PEG-IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1log10 and 3/3 of 2log10 of HDV-VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV-VL relapse was notified 24weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV-VL during the therapy (<100IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV-VL by 1log10 at 8 weeks and 1/1 by 2log10 at 28 week on-treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long-term clinical benefit (fibrosis reversibility and reduction in hepato-cellular carcinoma [HCC]).

Safety and Efficacy of Sofosbuvir Based Regimens in Treating Chronic ‎Hepatitis C Virus in Egyptian Patients: Real World Study: Single Center ‎Experience

Backgroundand study aims:Hepatitis C virus (HCV) is the main leading cause of liver disease in ‎Egypt. A new era of HCV treatment has been started with the evolution ‎of direct acting antiviral agents. Sofosbuvir (SOF)-based therapy was ‎introduced by the Egyptian ministry of health in 2014 in an attempt to ‎decrease disease burden. We aimed to evaluate efficacy and safety of ‎Sofosbuvir-based regimens in HCV Egyptian patients with compensated ‎liver disease‎. Patients and Method:‎This study was conducted in National Liver Institute, Menoufia‎University, Egypt. Seven hundred patients out of seven hundred fifty-‎eight chronic HCV patients with compensated liver disease who met the ‎inclusion criteria were included. According to treatment regimen patients ‎were divided to 4 groups; group 1 received Sofosbuvir (SOF), ‎Pegylated interferon (PEG-IFN) plus ribavirin (RBV), group 2 received ‎SOF plus RBV, group 3 received SOF and Simeprevir± RBV, group 4 ‎received SOF and Daclatasvir ±RBV‎.‎ Results:The overall SVR was 90.9%, 81.5%, 95% and 98% in groups 1, 2, 3, ‎and 4 respectively. SVR in patients with liver cirrhosis was 90.56, ‎‎79.16, 95 and 96% in the 4 groups respectively. In treatment ‎experienced patients, SVR was 86.8% in group 1, 78.3% in group 2, ‎‎100% in group 3 and 86.7% in group 4‎‎‎‎. Conclusion: Sofosbuvir plus daclatasvir with or without ribavirin is the safest ‎andmost effective SOF-based regimen in treatment of HCV Egyptian ‎patients with compensated liver disease‎‎‎‎.

New therapies for hepatitis delta virus infection.

Hepatitis delta virus (HDV) infection is a defective virus requiring hepatitis B virus (HBV) for its complete replication cycle. HDV is a small hepatotropic RNA virus and around 15 to 25 million people worldwide are living with chronic hepatitis delta (CHD) infection. However, the prevalence of HDV may be underestimated, and screening is frequently insufficient. HDV infection remains endemic in several regions including Central and West Africa, the Mediterranean basin, the Middle East, Eastern Europe, Northern Asia, certain areas of Southeast Asia and the Amazon basin of South America. The best preventive strategy to decrease HDV infection is to improve coverage of the prophylactic HBV vaccine. HDV infection may occur by HBV-HDV co-infection or superinfection, and the latter is usually more severe. CHD is associated with a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to HBV mono-infection. Pegylated interferon alpha (PEG-IFNα) therapy is limited by moderate effectiveness (around 20%) and its adverse effects. The entry inhibitor, bulevirtide (BLV, Hepcludex® ), which was recently approved in Europe at a dose of 2mg in sub-cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG-IFNα. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFNλ) (immunomodulator), lonafarnib (prenylation inhibitor) and nucleic acid polymers (Inhibitors of HBsAg release). In this review, we will present an update on CHD and future promising treatments.

Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort.

Real‐world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct‐acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post‐treatment survival of 4307 patients in the RESIST‐HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child‐Pugh A cirrhosis and 8.4% Child‐Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause‐specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA‐positive at last follow‐up. Sixty‐three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta −2.37, p < .001). Also, platelet count (HR 0.99, beta‐0.01, p = .007) and albumin value (HR 0.26, beta −1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta‐2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.

Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan.

Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100mg once daily for 12weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6-96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8-99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. SOF/VEL for 12weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.

Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment

ObjectiveData regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI)...

A narrative review of malnutrition in chronic liver disease.

Interest in research on malnutrition is decreasing due to thoughts that the problem of malnutrition has been solved in an age of over-nourishment or obesity and defining malnutrition is not uniform. This study aimed to critically appraise the prevalence of malnutrition according to various diagnostic tools and proportion of severity used in previous studies. A literature review was performed using a total of 16 studies published between 1980 and 2020 regarding malnutrition in patients with chronic liver disease. Most of the analyzed studies were conducted before 2010, and only a few studies were conducted after 2010. Nutrition assessment tool (NAT) and nutrition screening tool (NST) to explain malnutrition were distinguished; however, there was no clear distinction between them. NST often used questionnaires while NST used various malnutrition measuring tools. Our results show that, in the age of over-nourishment, reduction in malnutrition in chronic liver disease still hasn’t been significant. Malnutrition prevalence in studies published prior to 2,000 ranged between 13.3% and 85% (mean, 37.6%), whereas that in studies published after 2,000 ranged between 13.3% and 78.5% (mean, 35.2%). Malnutrition prevalence largely depends on the diagnostic tool and proportion of disease severity in the target population. The prevalence of malnutrition in patients with chronic liver diseases varies widely. This big difference is related to various diagnostic tools, mixed etiologies, and different disease severity in different studies. The prevalence of malnutrition was 36.4% (10–80.3%) in all patients with liver disease, 39.9% (13.3–80.3%) in compensated liver disease, and 44.1% (26.7–93.6%) in decompensated cirrhosis. Malnutrition prevalence was 38.2% and 23.7% in alcoholism-related and hepatitis C virus (HCV)-related diseases, respectively. Malnutrition also largely depended on the judgement tool. Malnutrition prevalence according to the diagnostic tool was approximately 28–85% for subjective global assessment (SGA), 30.8–78.5% for anthropometric approach, and 21–80.3% for clinical judgment. It became similar over time.

Bulevirtide for HBV and HDV infections

Hepatitis B virus (HBV) and its satellite virus hepatitis D (HDV) are common worldwide hepatotrophic infections responsible for cirrhosis and hepatocellular carcinoma (HCC). The more common HBV infection has several therapeutic regimens currently available for suppression of viral replication. However, a regimen leading to an effective sustained functional cure is still not available. In contrast, HDV infection, which causes the most severe form of chronic viral hepatitis and an increased rate of HCC, currently has no Food and Drug Administration (FDA)-approved treatment. Bulevirtide is a novel virion entry inhibitor which blocks the virion's hepatocyte pathway of entry, the hepatic sodium/taurocholate cotransporting polypeptide (NTCP) receptor, and is now a promising therapy for both infections. In July 2020 bulevirtide was authorized for use in the E.U. following a positive opinion by the European Medicines Agency (EMA) for the treatment of chronic HDV infection in HDV RNA-positive adult patients with compensated liver disease. In this paper we have examined the studies that led to this approval as well as studies examining the drug's efficacy in treating HBV.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.