Assessment of Sarcopenia Related Quality of Life Using SarQoL® Questionnaire in Patients With Liver Cirrhosis.

Introduction: Sarcopenia, malnutrition, physical deconditioning, and frailty contribute to a significantly altered quality of life (QoL) in patients with cirrhosis and sarcopenia. Aim: To investigate the sarcopenia-linked alterations of QoL by SarQoL® questionnaire in patients with end-stage liver disease. Methods: Consecutive patients with liver cirrhosis, admitted to our department between May and August 2021, completed the SarQoL® questionnaire by themselves. They were evaluated for sarcopenia according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP) definition [hand grip cut-offs and skeletal muscle index (SMI) calculation at CT scan]. Results: A total of 71 patients with liver cirrhosis were included in the study, with a median age of 54 years. Sarcopenia was present in 31.2% of patients with Child-Pugh class A, in 58.3% with class B, and in 93.5% with class C. The SarQoL® score was statistically significant and lower in Child-Pugh class C vs. class B and class A (70.2 vs. 66.5 vs. 52.5 points, p = 0.0002). The SarQoL® score was evaluated according to different complications of cirrhosis, with statistically significant lower scores in patients with sarcopenia (p < 0.0001), in patients with ascites requiring paracentesis (p = 0.0006), and in patients with hepatic encephalopathy (p < 0.0001). A cut-off level of 75.9 points for SarQoL® score can accurately detect sarcopenia in patients with end-stage liver disease [area under the receiver operating characteristic (AUROC) curve of.823, SE of 92.1%, SP of 45.5%, positive predictive value (PPV) and negative predictive value (NPV) of 66 and 83.3%, respectively, correctly classified 73.2% of cirrhotic patients with sarcopenia]. Conclusions: The use of SarQoL® questionnaire in cirrhotic patients can, at the same time, evaluate the quality of life and identify subjects with sarcopenia and altered QoL.

The impact of direct acting antivirals on hepatitis C virus disease burden and associated costs in four european countries.

BACKGROUND AND AIMS: We assessed the clinical and economic impact of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain. METHODS: An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015-2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID-19) was also developed. RESULTS: The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20-year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015-2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017-2019. The cost-savings ranged from € 45 to € 275 million. The investment needed to expand access to DAAs in 2015-2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID-19 will increase liver mortality in all countries. CONCLUSION: Direct-acting antivirals have significant clinical benefits and can bring substantial cost-savings over the next 20 years, reaching a Break-even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID-19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Dynamics of the Romanian waiting list for liver transplantation after changing organ allocation policy.

AIM: The aim of the present study was to characterize the dynamics of the Romanian waiting list (WL) for liver transplantation (LT) over two periods: 2004-2007 vs. 2008-2011. METHODS: 1,085 patients listed for LT during the time period 2004-2011 were included in our analysis. RESULTS: Death on the WL was significantly higher before 2008 (37% vs. 26.4%, p=0.0001) and risk of dying while on WL was 60% higher. Waiting time on the WL was 75% longer and time until LT was 102% longer before 2008 compared to the second time period (p=0.0001). After 2008, 62.3% of patients were listed for LT with Child Pugh class C compared to 22.1% before 2008 (p<0.0001). CONCLUSION: A significant reduction of mortality has been registered on the Romanian WL for LT after 2008, despite the increased severity of liver disease in patients listed for LT.

Cost-effectiveness of peginterferon alpha-2a and peginterferon alpha-2b combination regimens in genotype-1 naive patients with chronic hepatitis C.

BACKGROUND/AIMS: Pegylated interferons (Peg-IFNs) with ribavirin represent the standard treatment in chronic C viral hepatitis in Romania. Primary aim was to evaluate the cost-effectiveness of Peg-IFN alpha-2a plus ribavirin versus IFN alpha-2b plus ribavirin in genotype-1 patients in Romanian setting. The second end point was to make an indirect comparison of the cost-effectiveness of combination therapy of the two Peg-IFNs. METHODOLOGY: Published clinical data on sustained virological response rates (SVR) and early virological response rates (EVR) from more recent published studies were used for both combination therapies. A Markov model with seven health states was built. The reference patient was a 45-year-old male with chronic non-cirrhotic liver disease due to chronic HCV infection. Time horizon is patient lifetime. Published data on the natural history of hepatitis C, local mortality data, published utilities and local expertise were used for assessment of local procedures, resources used and costs. The perspective is that of the National Health Insurance Agency (NHIA). RESULTS: The incremental cost of treatment with Peg-IFN alpha-2a plus ribavirin is 19,056 Rol per LY gained and 27,175 Rol per QALY gained. A one-way sensitivity analysis showed that results are sensitive to the discount rate used, but they still are highly cost-effective. The indirect comparison of cost-effectiveness of Peg-IFNs combination therapies over IFN alpha-2b showed superiority of Peg-IFN alpha-2a and ribavirin therapy. CONCLUSION: This study demonstrates a higher cost-effectiveness of the current state-of-the art treatment with Peg-IFN alpha-2a with ribavirin over the standard IFN and ribavirin combination. Although a slight superiority of Peg-IFN alpha-2a over Peg-IFN alpha-2b combined regimen was shown in Romanian setting in terms of LYs and QALYs gained, there are no significant differences in cost-effectiveness of the two therapies.

Access to peginterferon plus ribavirin therapy for hepatitis C in Romania between 2002-2009.

BACKGROUND: An overall prevalence rate of HCV infection in Romanian adult population was recently estimated to be 3.23%. The proportion of treated patients with chronic hepatitis C in our country has never been assessed. AIMS: 1) to analyze the quality and quantity of antiviral therapy delivery; 2) to determine the proportion of patients being annually and ever treated with antiviral therapy in Romania and 3) to identify barriers against treatment of HCV infected-population in Romania. RESULTS: The number of annually treated patients remained relatively stable between 2002 and 2007 (1,813 patients treated with pegylated interferon and ribavirin in 2002 and 2,446 in 2007). There was a doubled increase in reimbursed treatment in 2008 and 2009 (4,503 and respectively 4,701 treated patients) due to a special campaign organized to increase awareness and prevention of HCV transmission. The median time to therapy approval varies from county to county; overall it is 10.23 months. A total number of 25,318 patients with chronic C hepatitis were treated between 2002-2009, corresponding to a cumulative proportion of 4.1% of the prevalent cases of HCV infection treated in Romania until 1st January 2010. The main limiting factor of access to antiviral therapy for hepatitis C in Romania remains the lack of funds. CONCLUSIONS: This is the first analysis of the nationwide practice for treatment of hepatitis C in Romania. Increased public health efforts are required to improve access to antiviral therapy for hepatitis C in Romania.

Projected dynamics of colonoscopic screening and surveillance for colorectal cancer.

BACKGROUND/AIMS: We used a simulation model of statistical analysis to estimate the cost and procedural burden of colorectal cancer (CRC) screening and surveillance using colonoscopy. METHODOLOGY: The estimated financial resources have been evaluated by multiplying half of the scheduled colonoscopies with the cost of one surveillance colonoscopy, dividing the result to the median time in which the procedures are performed, according to the Kaplan-Meier curve of scheduled procedures. RESULTS: Three hundred and thirty-eight patients (72.5%) were included in the registry for colonoscopic surveillance after a curative resection for colorectal cancer, 101 patients (21.7%) for follow-up after endoscopic polypectomies of adenomatous polyps, 21 patients (4.5%) for long lasting inflammatory bowel disease (IBD), and 2 patients (0.4%) for familial adenomatous polyposis. The projected dynamics and costs of colonoscopies scheduled for one year in our center indicate 11650 Euro/9.4 months spending for all procedures, 8450 Euro/8.8 months for surveillance after curative resection for CRC, 2525 Euro/24.9 months for surveillance after endoscopic polypectomies of adenomatous polyps and 525 Euro/6.8 months for screening for CRC in patients with long history of IBD, respectively. CONCLUSIONS: Screening and surveillance for CRC in a Romanian gastroenterology center represents an important activity in both workload and costs.

Costs and efficacy of "on demand" low-dose immunoprophylaxis in HBV transplanted patients: experience in the Romanian program of liver transplantation.

BACKGROUND: HBV in liver transplant (LT) patients is associated with good outcomes and the challenges are primarily focused around optimizing prophylactic regimens with hepatitis B immune globulin (HBIG) and minimizing related costs. AIM: To identify recurrence rates in patients transplanted for HBV or HBV+HDV infection in whom a combined "on demand" low-dose HBIG was used, maintaining low anti-HBs titres (not below 50 IU/L). METHODS: Medical records of 42 patients transplanted for HBV or HBV+HDV induced cirrhosis between April 2000 and September 2007 at Fundeni Clinical Institute were analyzed. Patients received immunoprophylaxis with lamivudine and HBIG (10,000 IU within anhepatic phase and daily within the first postoperative week, followed by 2,500 IU on demand). HBV recurrence rates and survival during follow-up were evaluated using the Kaplan Meier method. RESULTS: HBV recurrence rate was 4.8% after a median of 1.8 years. Three year patient survival rate was 70%. None of the patients died due to liver failure related to HBV recurrence. Using our "on demand" low-dose administration of HBIG, the total mean cost for HBIG and lamivudine for patient per month of survival was 598.3 Eur. The projected monthly cost for the "ideal" schedule/patient was 2,017 Eur. CONCLUSION: Individualization of immunoprophylaxis after LT for HBV related disease according to the lowest protective anti-HBs titers in combination with lamivudine is probably the best approach for non-replicative pre-LT patients in terms of costs and efficacy.