Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

BACKGROUND: Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. AIM: To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. METHODS: We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. RESULTS: 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. CONCLUSION: HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B.

BACKGROUND: Although the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease, there is a paucity of data evaluating body composition in patients with chronic hepatitis B (CHB). Beyond virus-related factors, nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded. AIM: To evaluate the association between components of sarcopenia and demographic, clinical, lifestyle, nutritional, and biochemical variables in CHB patients. METHODS: Dual-energy X-ray absorptiometry (DXA) was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for body mass index (ALMBMI). Muscle function was evaluated by hand grip strength (HGS) and the timed up and go test. Metabolic-associated fatty liver disease (MAFLD) was defined according to the criteria proposed by an international expert panel. A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level, respectively. RESULTS: This cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre (mean age, 48.5 ± 12.0 years; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated cirrhosis). The DXA-derived fat mass percentage was inversely correlated with the ALMBMI (r = - 0.87) and HGS (r = - 0.63). In the multivariable analysis, MAFLD, sedentarism and central obesity were positively and independently associated with low ALMBMI. MAFLD and central obesity were independently associated with low HGS. CONCLUSION: MAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B, independent of the liver disease stage.

Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in HCV patients as a prototype to monitor immunotherapy of infectious diseases.

In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.

Chronic hepatitis B and liver schistosomiasis: a deleterious association.

BACKGROUND: Chronic hepatitis B (CHB) and schistosomiasis are prevalent in several countries, but the impact of this association is unknown. We aimed to investigate the prevalence and morbidity of this co-infection in Minas Gerais, an endemic area of schistosomiasis in Brazil. METHODS: In total, 406 adults with CHB (HBsAg positive >6 months) were included in a cross-sectional study. CHB was classified as replicative (HBV DNA ≥ 2.000 IU/ml), and low replicative or inactive hepatitis B carriers (HBV DNA <2.000 IU/ml). Schistosomiasis was confirmed by epidemiological and clinical records. Liver biopsies were scored by METAVIR. The risk of severe fibrosis was estimated by multivariate analysis. RESULTS: Of the 406 patients, 64.8% (263) were male, and the median age was 45 years (IQR 35-54). In total, 57.9% (235) had replicative CHB, and 31.5% (128) had cirrhosis. Schistosoma mansoni was confirmed in 30.5% (124) patients, 81.5% (101) of which were male with a median age of 47 years (IQR 39.5-54). Of the co-infected patients, 61.3% (76) and 38.7% (48) had replicative and inactive CHB, respectively. Schistosomal portal fibrosis (PF) was detected in 69.4% (86/124) patients. Patients with replicative CHB and schistosomal PF had more advanced fibrosis and severe inflammation compared with patients without schistosomal PF (80.8% vs 43.6% for METAVIR F3-F4, p<0.01; 64.0% vs 39.8% for METAVIR A2-A3, p < 0.01). Age >50 years (OR = 1.10; 95% CI 1.06-1.14, p<0.001), male gender (OR = 2.61, 95% CI 1.12-6.09, p = 0.03), schistosomal PF (OR = 4.56, 95% CI 2.10-9.91, p<0.001) and alcoholism (OR = 2.46, 95% CI 1.16-5.19, p = 0.02) were independently associated with cirrhosis. CONCLUSIONS: The association between replicative CHB and schistosomal PF can be a risk factor for more severe liver disease, which can result in deleterious outcomes for patients from endemic areas.