Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

 Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. AIM: To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. MATERIAL AND METHODS: Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. RESULTS: Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). CONCLUSIONS: This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Transjugular intrahepatic portosystemic shunt in refractory ascites: clinical impact of left ventricular diastolic dysfunction.

BACKGROUND AND AIMS: Left ventricular diastolic dysfunction (LVDD) in cirrhotics are associated with circulatory dysfunction, hepatorenal syndrome (HRS) and heart failure in stressful conditions. Transjugular intrahepatic portosystemic shunt (TIPS) exacerbates the hyperdynamic circulation and challenges cardiac function. We evaluated the incidence and the impact of LVDD in cirrhotic candidates to TIPS for refractory ascites. METHODS: Among 135 patients who underwent TIPS for refractory ascites, 63 cases (child B/C 53/10, Na-model for end-stage liver disease 16.5 ± 0.9) who had 2D-transthoracic-echocardiography with tissue-Doppler-imaging pre-TIPS were retrospectively analysed (group A); in 23 cases cardiac and hormonal assessment before and after TIPS was available. 41 cirrhotics without refractory ascites treated by banding ligation for variceal re-bleeding were used as controls (group B). RESULTS: The prevalence of LVDD was higher in group A (59%; 22% with grade ≥2) as compared to group B (35%; 7% with grade ≥2) (P < 0.01 and P < 0.03). A lack of clinical response to TIPS occurred in 10 patients, all with LVDD (P < 0.03 vs. no LVDD) and in patients with grade ≥2 LVDD mostly (P < 0.02 vs. grade 1). Central venous pressure >20 mmHg after TIPS and left ventricular end-diastolic volume at basal were predictors of no response to TIPS (P = 0.01 and P = 0.004, respectively), which was an independent predictor of death. Elevated levels of NT-proBNP 3 days after TIPS were associated with advanced cardiac dysfunction (P = 0.005). CONCLUSION: NT-proBNP and careful LVDD investigation are useful to better select patients and to predict clinical response and mortality after TIPS.

L-carnitine and short chain ester in tears from patients with dry eye.

PURPOSE: The tear film is essential for the integrity of the ocular surface. In ocular diseases such as dry eye syndrome (DES), tear film osmolarity is increased relative to normal physiological conditions. DES can be caused by deficiency in lachrymation, hyperevaporation, or surface alterations. Carnitines, shown to have osmoregulatory properties, are thought to regulate tear film osmolarity, thus protecting the corneal surface from damage. We investigated the presence of carnitine in tears, compared tear carnitine concentrations in healthy subjects and in DES patients and speculate on carnitine's potential role as a protective agent in the tear film. METHODS: Tears were collected from 10 healthy subjects and 10 DES patients. Carnitine levels were assessed by high performance liquid chromatography-mass spectrometry. RESULTS: Carnitine and its derivatives were detected in the tear samples. In DES patients, concentrations were substantially lower than in healthy subjects; the mean concentrations were L-carnitine, 3.27 +/- 0.80 and 8.94 +/- 0.50 microMol/L; L-acetylcarnitine, 1.66 +/- 0.50 and 3.05 +/- 0.65 microMol/L; and L-propionylcarnitine, 0.30 +/- 0.11 and 0.57 +/- 0.13 microMol/L, in DES patients and healthy subjects, respectively. CONCLUSIONS: Although increased tear film osmolarity has been previously observed in DES patients, our study showed lower carnitine levels in DES patients than in healthy subjects, rather than the increased levels expected, although a causal relationship between carnitine levels and hyperosmolarity has not been established. The damage to ocular surface cells because of exposure to hypertonic tear film observed in DES may be partially because of an imbalance in the concentration of carnitine molecules in the tear film relative to the ocular surface cells. We propose, therefore, that carnitine solutions may have a role in preventing the adverse effects of observed hyperosmolarity and suggest that further studies are now warranted to investigate the clinical application of carnitine in the treatment of DES.

The aging eye and the role of L-carnitine and its derivatives.

The majority of ocular pathologies originate from a functional deterioration of intraocular tissues. This age-related deterioration often occurs as a result of changes within the eye. There is growing interest in the role of natural or synthetic compounds, such as carnitine, for blocking, or slowing, the progress of this deterioration. L-carnitine and its derivatives are involved in numerous physiological reactions, including sugar aerobic metabolism, oxidative phosphorylation, fatty acid oxidation and osmosis. While carnitine levels in human ocular tissue are unknown, animal studies indicate that carnitine is differentially distributed within the eye with the highest concentrations reported in the iris, ciliary body and the choroid-retina. In patients with age-related macular degeneration (AMD), acetyl-L-carnitine improved four parameters of visual function, including visual field mean defect, visual acuity, foveal sensitivity and ocular fundus alterations. L-carnitine has also demonstrated antioxidant properties in animal models of oxidative damage. This article reviews the potential use of L-carnitine and its derivatives in age-related ocular pathologies, such as AMD, cataract, glaucoma and dry eye syndrome.

Ocular disorders secondary to systemic disease and the potential role of carnitines.

L-carnitine has a wide-ranging role in several physiological processes, but perhaps most significantly in long-chain fatty acid oxidation in the mitochondrial matrix. Osmolytic (or osmoprotective) properties have also been suggested for the compound. Importantly, the ability of L-carnitine to improve insulin sensitivity in insulin-resistant diabetic patients may, together with the agent's antioxidant and antiapoptotic activity, provide some degree of protection against the progression of diabetic retinopathy. L-carnitine may also protect against the deleterious effects of ocular ischaemic syndrome, and, indeed, acetyl-L-carnitine has been shown to significantly improve retinal damage and visual acuity in patients with monolateral or bilateral retinal artery occlusion. The antioxidant, antiapoptotic and osmolytic properties of L-carnitine also suggest that this agent may have valuable clinical utility in neurotrophic keratopathy and bullous keratopathy. Thus, further detailed investigation of the important clinical potential of L-carnitine in various ocular conditions (e.g. diabetic retinopathy, ocular ischaemic syndrome, neurotrophic keratopathy and bullous keratopathy) that occur secondary to systemic diseases is now clearly warranted.

Inherited ocular disorders, ophthalmic procedures and carnitines.

L-carnitine plays a role in physiological reactions throughout the body, including sugar aerobic metabolism, oxidative phosphorylation and, most importantly, fatty acid oxidation. In addition, L-carnitine has antiapoptotic, antioxidative and osmolytic properties, which may be useful in the treatment of ocular pathologies (e.g. retinitis pigmentosa [RP] and keratoconus), in corneal tissue repair and in ophthalmic procedures (e.g. photorefractive keratectomy and laser-assisted subepithelial keratectomy [LASEK]). Preliminary studies have suggested that L-carnitine supplementation may be useful in patients with RP. Although studies are warranted to ascertain the benefit of L-carnitine in the LASEK procedure, potentially it could be used instead of alcohol to facilitate epithelial detachment and as a hypo-osmotic solution in the fluid filler used in therapeutic photoablation. Furthermore, its antiapoptotic properties may improve cellular migration, proliferation and adhesion of keratocytes, epithelial cells and endothelial cells, which may be useful in the corneal repair process. Similarly, L-carnitine in high concentrations may prove useful in cross-linking parasurgical treatment of keratoconus, owing to its osmolytic and non-cytotoxic properties.

Hepatitis B in patients with hematological diseases: An update.

Hepatitis B virus (HBV) reactivation (HBVr) in patients undergoing immunosuppressive therapy is still a hot topic worldwide. Its prevention and management still represents a challenge for specialists dealing with immunosuppressed patients. Aim of this paper is to provide a critical review of the relevant information emerged in the recent literature regarding HBV reactivation following immunosuppressive treatments for oncohematological tumors. A computerized literature search in MEDLINE was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. Articles published only in abstract form and case reports not giving considerable news were excluded. Clinical manifestation of HBVr can be manifold, ranging from asymptomatic self-limiting anicteric hepatitis to life-threatening fulminant liver failure. In clusters of patients adverse outcomes are potentially predictable. Clinicians should be aware of the inherent risk of HBVr among the different virological categories (active carriers, occult HBV carriers and inactive carriers, the most intriguing category), and classes of immunosuppressive drugs. We recommend that patients undergoing immunosuppressive treatments for hematological malignancies should undergo HBV screening. In case of serological sign(s) of current or past infection with the virus, appropriate therapeutic or preventive strategies are suggested, according to both virological categories, risk of HBVr by immunosuppressive drugs and liver status. Either antiviral drug management and surveillance and pre-emptive approach are examined, commenting the current international recommendations about this debated issue.

Sarcopenia Predicts Reduced Survival in Patients with Hepatocellular Carcinoma at First Diagnosis

Abstract: Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.