Evaluation of ChatGPT as a Counselling Tool for Italian-Speaking MASLD Patients: Assessment of Accuracy, Completeness and Comprehensibility.

BACKGROUND: Artificial intelligence (AI)-based chatbots have shown promise in providing counseling to patients with metabolic dysfunction-associated steatotic liver disease (MASLD). While ChatGPT3.5 has demonstrated the ability to comprehensively answer MASLD-related questions in English, its accuracy remains suboptimal. Whether language influences these results is unclear. This study aims to assess ChatGPT's performance as a counseling tool for Italian MASLD patients. METHODS: Thirteen Italian experts rated the accuracy, completeness and comprehensibility of ChatGPT3.5 in answering 15 MASLD-related questions in Italian using a six-point accuracy, three-point completeness and three-point comprehensibility Likert's scale. RESULTS: Mean scores for accuracy, completeness and comprehensibility were 4.57 ± 0.42, 2.14 ± 0.31 and 2.91 ± 0.07, respectively. The physical activity domain achieved the highest mean scores for accuracy and completeness, whereas the specialist referral domain achieved the lowest. Overall, Fleiss's coefficient of concordance for accuracy, completeness and comprehensibility across all 15 questions was 0.016, 0.075 and -0.010, respectively. Age and academic role of the evaluators did not influence the scores. The results were not significantly different from our previous study focusing on English. CONCLUSION: Language does not appear to affect ChatGPT's ability to provide comprehensible and complete counseling to MASLD patients, but accuracy remains suboptimal in certain domains.

Diagnosis and non-invasive assessment of MASLD in type 2 diabetes and obesity.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease and an important cause of cirrhosis and hepatocellular carcinoma. It is strongly associated with type 2 diabetes and obesity. Because of the huge number of patients at risk of MASLD, it is imperative to use non-invasive tests appropriately. AIMS: To provide a narrative review on the performance and limitations of non-invasive tests, with a special emphasis on the impact of diabetes and obesity. METHODS: We searched PubMed and Cochrane databases for articles published from 1990 to August 2023. RESULTS: Abdominal ultrasonography remains the primary method to diagnose hepatic steatosis, while magnetic resonance imaging proton density fat fraction is currently the gold standard to quantify steatosis. Simple fibrosis scores such as the Fibrosis-4 index are well suited as initial assessment in primary care and non-hepatology settings to rule out advanced fibrosis and future risk of liver-related complications. However, because of its low positive predictive value, an abnormal test should be followed by specific blood (e.g. Enhanced Liver Fibrosis score) or imaging biomarkers (e.g. vibration-controlled transient elastography and magnetic resonance elastography) of fibrosis. Some non-invasive tests of fibrosis appear to be less accurate in patients with diabetes. Obesity also affects the performance of abdominal ultrasonography and transient elastography, whereas magnetic resonance imaging may not be feasible in some patients with severe obesity. CONCLUSIONS: This article highlights issues surrounding the clinical application of non-invasive tests for MASLD in patients with type 2 diabetes and obesity.

A prospective study on the prevalence of MASLD in people with type-2 diabetes in the community. Cost effectiveness of screening strategies.

BACKGROUND AND AIMS: As screening for the liver disease and risk-stratification pathways are not established in patients with type-2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost-utility of different screening strategies for MASLD in the community. METHODS: Consecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score-4 (FIB-4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality-adjusted life year (QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) over a lifetime horizon. RESULTS: Of 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB-4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB-4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost-utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB-4. CONCLUSION: Screening for MASLD in the diabetic population in primary care is cost-effective and should become part of a holistic assessment. However, traditional screening strategies, including FIB-4 and ELF, underestimate the presence of significant liver disease in this setting.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes.

BACKGROUND AND AIMS: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D). METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH. CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. METHODS AND RESULTS: Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. CONCLUSION: NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

Optimization of hepatitis C virus screening strategies by birth cohort in Italy.

BACKGROUND AND AIMS: Cost-effective screening strategies are needed to make hepatitis C virus (HCV) elimination a reality. We determined if birth cohort screening is cost-effective in Italy. METHODS: A model was developed to quantify screening and healthcare costs associated with HCV. The model-estimated prevalence of undiagnosed HCV was used to calculate the antibody screens needed annually, with a €25 000 cost-effectiveness threshold. Outcomes were assessed under the status quo and a scenario that met the World Health Organization's targets for elimination of HCV. The elimination scenario was assessed under five screening strategies. RESULTS: A graduated birth cohort screening strategy (graduated screening 1: 1968-1987 birth cohorts, then expanding to 1948-1967 cohorts) was the least costly. This strategy would gain approximately 144 000 quality-adjusted life years (QALYs) by 2031 and result in an 89.3% reduction in HCV cases, compared to an 89.6%, 89.0%, 89.7% and 88.7% reduction for inversed graduated screening, 1948-77 birth cohort, 1958-77 birth cohort and universal screening, respectively. Graduated screening 1 yielded the lowest incremental cost-effectiveness ratio (ICER) of €3552 per QALY gained. CONCLUSIONS: In Italy, a graduated screening scenario is the most cost-effective strategy. Other countries could consider a similar birth cohort approach when developing HCV screening strategies.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. METHODS: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. RESULTS: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. CONCLUSIONS: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. LAY SUMMARY: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.

Is global elimination of HCV realistic?

The elimination of hepatitis C virus (HCV) has been made possible through the availability of new antiviral drugs which may now be administered to all patients with HCV infection, even those with decompensated cirrhosis. The goal of the World Health Organization (WHO) is to reduce the incidence of chronic hepatitis infection from the current 6-10 million to 0.9 million cases of chronic infections by 2030, and annual deaths from 1.4 million to fewer than 0.5 million. Achieving these targets will require full implementation of epidemiological knowledge of HCV infection, screening and testing practices and strategies to link HCV patients to care. This review will focus on the current state of knowledge in the epidemiology of HCV and what can be done to increase patient awareness and reduce the barriers to treatment. Furthermore, we will discuss the role of HCV clearance on the control of HCV-related outcomes.

Current and future HCV therapy: do we still need other anti-HCV drugs?

Eradication of hepatitis C virus (HCV) infection, at least in compensated patients, can help improve the outcomes of liver disease such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation, as well as perhaps extra-hepatic complications such as diabetes and cardiovascular risk. In the past few years, the landscape of antiviral therapy has evolved at a breathtaking pace from pegylated interferon (PEG-IFN) plus ribavirin (RBV) (PEG-IFN/RBV) to IFN-based strategies combining direct acting antivirals (DDAs) with PEG-IFN/RBV and finally IFN-free combinations of DAAs. In particular with these most recent developments, treatment regimens have become shorter, safer and even more effective, with a wide range of indications. Nevertheless, research continues and newer antiviral drugs are still under development. At a point when a >90% sustained virological response (SVR) is being claimed with all new available regimens, pharmacological and clinical research should be addressing unresolved areas, such as cases of suboptimal SVR or to increase effectiveness rather than pursuing the development of new 'me-too' drugs. The issues which should be given priority for further development include the following: Improving the results of IFN-free regimens in patients with genotype 3 (HCV-3) infection. Identifying the indications for the treatment in patients with compensated and decompensated cirrhosis. Identifying standardized or personalized backup strategies in patients who do not respond to IFN-free regimens. Finally, because of financial constraints, the high cost of IFN-free strategies prevents their universal use in CHC patients and coverage by national healthcare systems. Thus, efforts must be made to document cost-effectiveness in all clinical scenarios and to develop more affordable IFN-free regimens.

Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C.

BACKGROUND: We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. METHODS: Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro, at 2013 value), life-years gained, quality-adjusted life year, and incremental cost-effectiveness ratio. The robustness of the results was evaluated by multivariable probabilistic sensitivity analyses. RESULTS: According to the baseline predictors of sustained virological response (genotype 1b, low viral load, fibrosis F0-F3, and body mass index) and the 1Log drop of HCV-RNA after the dual therapy lead-in period, boceprevir was cost-effective in different patient profiles. CONCLUSIONS: In untreated genotype 1b chronic hepatitis C patients, the cost-effectiveness of boceprevir-based triple therapy widely ranges according to different profiles of sustained virological response predictors, allowing optimization and personalization of triple therapy.

Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C.

BACKGROUND & AIMS: In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign - bright liver echo pattern (BLEP) - on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC. METHODS: Patients (n=618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe. RESULTS: Male gender (p=0.04), steatosis as continuous variable (p<0.001), severity of necroinflammation (p=0.02) and stage of fibrosis (p<0.001) were associated with LSM by multivariate linear regression analysis. Among patients within the same fibrosis stages (F0-F2 and F3-F4; F0-F3 and F4), mean LSM values, expressed in kPa, were significantly higher in subjects with moderate-severe steatosis (⩾20% at liver biopsy) compared with those without, as well as in patients with BLEP on US compared with their counterpart. In subjects without severe fibrosis (F0-F2) and without cirrhosis (F0-F3), a higher rate of false-positive LSM results was observed in patients with steatosis ⩾20% compared with those without (F0-F2: 35.3% vs. 17.9%; F0-F3: 38.9% vs. 16.6%), and in patients with BLEP on US (F0-F2: 28.0% vs. 18.3%; F0-F3: 29.7% vs. 17.8%) compared with their counterpart. CONCLUSIONS: In patients with G1 CHC, the presence of moderate-severe steatosis, detected by histology or by US, should always be taken into account in order to avoid overestimations of liver fibrosis assessed by TE.

Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C.

UNLABELLED: We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Cost of SOF was assumed to be € 3,500 per week, i.e., the price generating a willingness-to-pay threshold of € 25,000 per LYG compared with TVR in the entire population of untreated G1 patients. The robustness of the results was evaluated by one-way deterministic and multivariate probabilistic sensitivity analyses. SOF was cost-effective compared with BOC in all strategies with the exception of cirrhosis and IL28B CC patients. In comparison with TVR-based strategies, SOF was cost-effective in IL28B CT/TT (ICER per LYG € 22,229) and G1a (€ 19,359) patients, not cost-effective in IL28B CC (€45,330), fibrosis F0-F3 (€ 26,444), and in cirrhosis (€ 34,906) patients, and dominated in G1b patients. The models were sensitive to SOF prices and to likelihood of sustained virological response. CONCLUSION: In untreated G1 CHC patients, SOF-based TT may be a cost-effective alternative to first-generation protease inhibitors depending on pricing. The cost-effectiveness of SOF improved in IL28B CT/TT and G1a patients. SOF was dominated by TVR in G1b patients even if, in clinical practice, this issue could be counterbalanced by the good tolerability profile of SOF and by the shorter treatment duration.

Cost-effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C.

BACKGROUND & AIMS: Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC. METHODS: The available published literature provided the data source. The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro at 2012 value), life years gained (LYG), quality adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER).The robustness of the results was evaluated by one-way deterministic and multivariable probabilistic sensitivity analyses. RESULTS: In RR patients, ICER per LYG compared to no therapy was €9555 for BOC-LEAD-IN-RR and €7910 for TVR-LEAD-IN-RR, being BOC dominated by TVR. In PAR patients, ICER for LYG was €11,947 for BOC-LEAD-IN-PAR and €14,931 for TVR-PAR, being TVR cost-effective compared to BOC (ICER for QALY €22,258). In NR patients, ICER for LYG was €26,499 for TVR-LEAD-IN-NR. The models were sensitive to likelihood of sustained virological response and to BOC/TVR prices. CONCLUSIONS: 1st generation HCV PI is highly cost-effective compared to no therapy in RR and PAR G1 CHC patients. TVR dominated BOC in RR, and was cost-effective compared to BOC in PAR patients. In NR patients an assessment of the response after a lead-in period should be performed to improve safety and cost-effectiveness.

Non invasive indexes for the assessment of patients with non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) affects about 20%-30% of the general population, and its clinical relevance arises from the fact that 20%-30% of these subjects develop non-alcoholic steatohepatitis (NASH), a condition at risk of cirrhosis progression. In addition NAFLD, and in particular NASH patients, are also at high risk of cardiovascular alterations, suffering overall from an increased liver and no liver-related events of risk and death. At the moment liver biopsy is the gold standard for a correct evaluation of NASH and fibrosis among NAFLD patients. However, the high and increasing prevalence of NAFLD has triggered an intensive search for alternative and non-invasive methods for evaluating disease severity. Specifically we can distinguish two main groups of non-invasive methodologies, namely 'serum markers' that use clinical and/or biochemical variables, and methodologies derived from elaboration of parameters arising from liver imaging techniques. All these tools showed encouraging results, even though their utility in clinical practice in the individual patients is still under debate. Therefore further efforts are needed in order to generate non-invasive algorithms that correctly assess liver damage in NAFLD patients. In particular, it should be interesting to perform gender-specific analysis, by combining old and new tools, with the aim to generate more accurate scores. Finally we think that non-invasive scores should not only be able to correctly classify the severity of liver disease in NAFLD patients, but also predict liver and non-liver related morbidity and mortality, further acting as time-dependent markers of liver and systemic disease activity. This review summarizes the present knowledge on noninvasive diagnosis in NAFLD patients, and suggest future directions for this complex research area.

Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma.

UNLABELLED: The purpose was to assess the cost-effectiveness of sorafenib in the treatment of hepatocellular carcinoma (HCC) patients incorporating current prices and the results of the recent published field practice SOraFenib Italian Assessment (SOFIA) study. We created a Markov Decision Model to evaluate, in a hypothetical cohort of Caucasian male patients, aged 67 years with Barcelona Clinic Liver Cancer (BCLC) C HCC, or BCLC B HCC who were unfit or failed to respond to locoregional therapies, well compensated cirrhosis, and with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG), the cost-effectiveness of the following strategies: (1) full or dose-adjusted sorafenib for BCLC B and C patients together; (2) full or dose-adjusted sorafenib for BCLC B patients; (3) full or dose-adjusted sorafenib for BCLC C patients. Outcomes include quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). In the base-case analysis dose-adjusted sorafenib was the most effective of the evaluated strategies. For dose-adjusted sorafenib, QALY was 0.44 for BCLC B and C patients together, 0.44 for BCLC C patients, and 0.38 for BCLC B patients. The ICER of dose-adjusted sorafenib compared with BSC was €34,534 per QALY gained for BCLC B and C patients together, €27,916 per QALY gained for BCLC C patients, and €54,881 per QALY gained for BCLC B patients. Results were sensitive to BSC survival rate, and sorafenib treatment duration. CONCLUSION: In daily practice dose-adjusted, but not full-dose, sorafenib is a cost-effective treatment compared to BSC in intermediate and advanced HCC.

Therapeutic algorithms for chronic hepatitis C in the DAA era during the current economic crisis: whom to treat? How to treat? When to treat?

The advent of triple therapy (TT) with first-generation protease inhibitors boceprevir (BOC) and telaprevir (TVR) in addition to pegylated interferon and ribavirin resulted in a significant gain in terms of sustained virological response (SVR) when treating naive or previous treated patients with genotype 1 (G1) chronic hepatitis C (CHC). This gain is partly balanced by the increased complexity of treatment and by the raised costs and risks of therapy, making necessary to optimize the indication to TT.Specifically, the identification of patient needing to TT over DT, the choice of the more correct therapeutic approach according to baseline and on treatment SVR predictors, and the timing of antiviral treatment, appear key issues to evaluate when considering TVR or BOC-based therapies.Along this line, further efforts aimed to optimize the current TT regimens are still needed, especially in under-represented groups of patients in phase 3 studies such as those with cirrhosis, where post-marketing data are giving interesting evidences.

Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.

UNLABELLED: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G(1) ) chronic hepatitis C (CHC). We assessed the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G(1) CHC. We created a Markov Decision Model to evaluate, in untreated Caucasian patients age 50 years, weight 70 kg, with G(1) CHC and Metavir F2 liver fibrosis score, for a time horizon of 20 years, the cost-effectiveness of the following five competing strategies: 1) boceprevir response-guided therapy (BOC-RGT); 2) boceprevir IL28B genotype-guided strategy (BOC-IL28B); 3) boceprevir rapid virologic response (RVR)-guided strategy (BOC-RVR); 4) telaprevir response-guided therapy (TVR-RGT); 5) telaprevir IL28B genotype-guided strategy (TVR-IL28B). Outcomes included life-years gained (LYG), costs (in 2011 euros) and incremental cost-effectiveness ratio (ICER). In the base-case analysis BOC-RVR and TVR-IL28B strategies were the most effective and cost-effective of evaluated strategies. LYG was 4.04 with BOC-RVR and 4.42 with TVR-IL28B. ICER compared with DT was € 8.304 per LYG for BOC-RVR and € 11.455 per LYG for TVR-IL28B. The model was highly sensitive to IL28B CC genotype, likelihood of RVR and sustained virologic response, and BOC/TVR prices. CONCLUSION: In untreated G(1) CHC patients age 50 years, TT with first-generation protease inhibitors is cost-effective compared with DT. Multiple strategies to reduce costs and improve effectiveness include RVR or genotype-guided treatment.