The Presence of Myosteatosis Is Associated with Age, Severity of Liver Disease and Poor Outcome and May Represent a Prodromal Phase of Sarcopenia in Patients with Liver Cirrhosis.

BACKGROUND/AIMS: Myosteatosis implies impaired muscle quality. The aim of the study was to investigate the association of myosteatosis with other muscle abnormalities and its role in the prognosis of liver cirrhosis (LC). METHOD: Skeletal muscle index (SMI) and myosteatosis were measured by computed tomography. Myosteatosis was defined as muscle radiodensity and evaluated according to dry body mass index (BMI). Median values and interquartile range were used for continuous and count (percentage) for categorical variables. RESULTS: A total of 197 consecutive patients were included (age 61 (IQR 52-68); 67% male; MELD score 11 (interquartile range 7.5-16)). Myosteatosis was identified in 73.6% and sarcopenia in 44.6% of patients. Myosteatosis was positively associated with age (p = 0.024) and Child-Pugh (p = 0.017) and inversely associated with SMI (p = 0.026). Patients with myosteatosis exhibited lower 360-day survival (log-rank p = 0.001) compared to those without it. MELD (p < 0.001) and myosteatosis (p = 0.048) emerged as negative prognostic factors of survival in multivariate model. Individuals combining low muscle strength and impaired muscle quality and quantity displayed more advanced LC, impaired muscle performance, lower BMI (p < 0.001 each) and a three times higher mortality rate compared to those with low muscle quality alone. CONCLUSIONS: The presence of myosteatosis was associated with advanced age, low skeletal mass and more severe LC. Myosteatosis was associated with poor prognosis and may represent a prodromal phase of muscle degeneration before the development of sarcopenia.

HERACLIS-TAF: a multi-centre prospective cohort study on 2-year safety and efficacy of tenofovir alafenamide in patients with chronic hepatitis B with renal and/or bone disorders or risks.

BACKGROUND: Tenofovir alafenamide (TAF) has exhibited a favourable safety profile on estimated glomerular filtration (eGFR) and bone mineral density (BMD), but has not been extensively studied in patients with renal impairment and/or BMD disorders. AIMS: To assess predictors of eGFR changes and other safety and efficacy outcomes during 24-month TAF therapy in patients with chronic hepatitis B with renal and/or BMD disorders/risks. METHODS: Adult patients who started TAF at 13 clinics throughout Greece were prospectively included. Main exclusion criteria were hepatitis D, active malignancy and bisphosphonates recent use. MDRD formula was used for eGFR estimation. RESULTS: TAF was initiated in 176 patients (91% switched from another agent). At 12 and 24 months, HBV DNA was undetectable in 97% and 100%, and ALT was normal in 96% and 95% of patients. Median ALT decreased from baseline to month 12/24 (p < 0.001). Mean eGFR decreased from previous treatment initiation to baseline (p < 0.001), increased at 12 months and remained stable at 24 months (p ≤ 0.001). An increase in eGFR of >3 ml/min at 12 month was observed in 50% of patients and was associated mainly with baseline eGFR 30-60 ml/min. In patients with baseline phosphate <2.5 mg/dl, mean serum phosphate increased at month-12/24 (p < 0.001). Median BMD did not change significantly from baseline to 12 months but improved at 24 months (p = 0.001). CONCLUSIONS: In mostly switched patients with renal and/or BMD disorders/risks, eGFR improved after 12-24 months of TAF treatment, especially in patients with baseline eGFR 30-60 ml/min. TAF may also improve low serum phosphate, BMD and ALT, whereas it maintains or induces virological suppression.

Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection.

OBJECTIVES: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, the clinical relevance of low viremia levels remains unclear. We evaluated the clinical significance of a single baseline serum HBV DNA measurement by a quantitative polymerase chain reaction (PCR) assay in this setting. METHODS: In total, 196 patients with HBeAg-negative chronic HBV infection (62 inactive carriers, 134 with chronic hepatitis B) were studied. ALT activity was normal at baseline in 25/134 HBeAg-negative chronic hepatitis B patients (18.7%), whereas it remained normal throughout follow-up in all inactive carriers. RESULTS: HBV DNA was <30,000 copies/ml in 14 (10.5%) and <100,000 copies/ml in 17 (12.9%) HBeAg-negative chronic hepatitis B patients, whereas it was <30,000 copies/ml in all inactive carriers (undetectable in 14). In particular, HBV DNA levels were <100,000 copies/ml in eight (32%) and <30,000 copies/ml in five (20%) of the 25 patients with HBeAg-negative chronic hepatitis B and normal baseline ALT values. HBV DNA levels with a cut-off at 30,000 or 100,000 copies/ml could correctly classify 92.9% or 91.3% of patients with HBeAg-negative chronic HBV infection, whereas ALT or IgM anti-HBc (IgM class antibody to HBV core antigen) index > 0.200 could correctly classify only 87.2% and 82.1% of patients, respectively. A combined HBV DNA and IgM anti-HBc index performed better by correctly classifying 94.4% of cases. CONCLUSIONS: Serum HBV DNA levels evaluated by sensitive quantitative PCR assays can be used for differentiation between HBeAg-negative chronic hepatitis B and inactive hepatitis B surface antigen carrier state, but the cut-off level should be set at approximately 30,000 copies/ml and certainly lower than the recently suggested level of 100,000 copies/ml.

Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era.

Post-transplant prophylaxis with hepatitis B immune globulin (HBIG) has significantly reduced hepatitis B virus (HBV) recurrence rates, but it is rather ineffective in patients with pretransplant viremia. Moreover, long-term HBIG administration is very expensive and may be associated with emergence of escape HBV mutants. Lamivudine has been widely used in the management of HBV transplant patients. Pretransplant lamivudine lowers HBV viremia, decreasing the risk of post-transplant HBV recurrence, but to try and minimize development of resistant HBV strains, it should start within the last 6 months of the anticipated transplantation timing. Preemptive post-transplant lamivudine monotherapy is associated with progressively increasing HBV recurrence rates, but combined therapy with lamivudine and HBIG at relatively low dosage is currently the most effective approach in this setting, even in HBV-DNA-positive patients, who also receive lamivudine in the pretransplant period. The most frequent therapy for post-transplant HBV recurrence is lamivudine, but the increasing resistance rates represent a rather challenging problem. Adefovir dipivoxil and entecavir are currently the most promising agents for lamivudine-resistant HBV strains. All these advances in anti-HBV therapy have made HBV liver disease an indication for liver transplantation irrespective of viral replication status, a complete turn around from 10 years ago.