Propranolol reduces systemic oxidative stress and endotoxemia in cirrhotic patients with esophageal varices.

BACKGROUND: The aim of the study was to investigate the effect of propranolol on systemic oxidative stress and endotoxemia in patients with liver cirrhosis and clinically significant portal hypertension evidenced by the presence of esophageal varices. METHODS: Fourteen patients with liver cirrhosis and esophageal varices, not previously been treated with non-selective beta-blockers (NSBB), were prospectively started on propranolol and followed up for three months. Serum early and late lipid peroxidation products (lipid hydroperoxides [LOOH] and malondialdehyde [MDA], respectively), and endotoxin concentrations in peripheral blood were measured. Fourteen age- and sex-matched healthy individuals were used as controls. RESULTS: Patients with liver cirrhosis presented significantly higher systemic oxidative stress and endotoxin concentrations compared to healthy controls (P<0.001). Propranolol treatment for one month significantly reduced serum MDA (P<0.05), LOOH (P<0.01), and endotoxin levels (P<0.01) compared to pre-treatment values, whilst LOOH reached control levels. At three months of propranolol treatment, serum LOOH did not differ significantly from the one-month values, whilst serum endotoxin and MDA levels were further reduced between 3- and 1-month period (P<0.05 and P<0.01, respectively), with the latter reaching control levels. Amelioration of systemic endotoxemia at the one- and three-month follow-up intervals (compared to pre-treatment values) was not correlated with the respective reductions in serum MDA and LOOH. CONCLUSIONS: This is the first study to show that NSBB treatment in liver cirrhosis exerts a significant systemic antioxidant action. This effect seems to be, at least partly, independent of their beneficial effects on intestinal barrier function and endotoxemia.

Lactate serum concentrations during treatment with nucleos(t)ide analogues in hepatitis B with or without cirrhosis.

OBJECTIVE: The aim of this study is to evaluate the clinical implications of lactate concentrations in patients with hepatitis B with or without cirrhosis during treatment with nucleos(t)ide analogues. PATIENTS AND METHODS: One hundred and seven consecutive patients with chronic hepatitis B and median age 57 (24-85) years were prospectively included. Lactate concentrations were measured at baseline and at 12, 24, 36, 48, and 60 months following the baseline measurements. Eight (n=8, 7.5%) patients received lamivudine, 38 (n=38, 35.5%) patients received tenofovir, 34 (n=34, 31.8%) patients received entecavir, and 27 (n=27, 25.2%) patients received combined therapy. RESULTS: None of the patients developed lactic acidosis during follow-up [median: 58 (6-155) months]. Overall, no trends of the lactic acid evolution were observed over time; however, there was a nonsignificant increasing trend in patients with cirrhosis up to 24 months of treatment. This increasing trend was significant in female patients with cirrhosis (P=0.016). The age of the patients, the presence of cirrhosis, and hepatocellular carcinoma were strongly associated with the survival of all patients. In the group of cirrhotic patients, the only independent prognostic factor that was associated with patients' survival was the Child-Pugh class. CONCLUSION: None of the patients developed lactic acidosis. There is an indication of an increasing trend of lactic acid levels up to 24 months of therapy in female cirrhotic patients.

Male hepatitis C patients' sexual functioning and its determinants.

OBJECTIVE: The aim of the study was to detect sexual impairment in male hepatitis C virus patients and determine its associations. PATIENTS AND METHODS: A total of 61 male hepatitis C virus patients were enrolled in this cross-sectional study. Sexual functioning was assessed using the International Index of Erectile Function. Health-related quality of life (HRQOL) was evaluated using the Greek version of the Short Form 36 Health Survey, and the presence and severity of anxiety and depression were assessed using the Greek version of the Hospital Anxiety and Depression Scale. RESULTS: Noncirrhotic patients showed clinically significant dysfunction, mainly in intercourse (59.6%) and overall satisfaction (57.4%). Erectile functioning and desire were correlated with depression (r=-0.520, P=0.000 and r=-0.473, P=0.000), anxiety (r=-0.443, P=0.000 and r=-0.428, P=0.001), physical (r=0.427, P=0.001 and r=0.329, P=0.012), and mental (r=0.379, P=0.003 and r=0.432, P=0.001) HRQOL, platelet count (r=-0.357, P=0.012 and r=0.366, P=0.010), and international normalized ratio (INR) levels (r=-0.373, P=0.013 and r=-0.440, P=0.003). Erection was also correlated with albumin levels (r=0.310, P=0.032). Orgasmic functioning was associated significantly with platelet count (r=0.322, P=0.024) and INR levels (r=-0.425, P=0.004). Intercourse satisfaction was significantly related to depression (r=-0.435, P=0.001) and anxiety (r=-0.335, P=0.008) levels, physical (r=0.374, P=0.004) and mental (r=0.300, P=0.022) HRQOL, platelet count (r=0.333, P=0.020), and INR levels (r=-0.373, P=0.013), and overall satisfaction was significantly correlated with depressive (r=-0.435, P=0.001) and anxiety (r=-0.278, P=0.033) symptoms, mental HRQOL (r=0.340, P=0.010), platelet count (r=0.316, P=0.029), and INR levels (r=-0.332, P=0.030). CONCLUSION: Hepatitis C is accompanied by poor sexual functioning even in the absence of cirrhosis and different correlations emerge for distinct subdomains of male sexuality.

Could antioxidants be the "magic pill" for cirrhosis-related complications? A pathophysiological appraisal.

Patients with liver cirrhosis are prone to serious complications by almost all systems, leading to high morbidity rates and even death. Although the functional and structural derangement of diverse vital organs developed in the course of advanced liver disease is the result of one entity (cirrhosis) there are various treatment modalities for each system's complications, which are often ineffective. Identification of the link which connects the complications of cirrhosis from diverse systems might lead to a global, simple and more effective treatment approach for patients with cirrhosis. Accumulating evidence from experimental and clinical studies suggests that intestinal barrier dysfunction and subsequent gut-derived endotoxemia represent an important common pathogenetic mechanism in the development of diverse complications of cirrhosis. Intestinal oxidative stress seems to be a pivotal factor of gut barrier dysfunction in cirrhosis through promotion of enterocyte apoptosis, modulation of intestinal tight junctions and impairment of intestinal brush border function. In parallel, oxidative stress plays a fundamental role in the aggravation of liver injury and in the structural and/or functional derangements of diverse organs complicating the course of cirrhosis. Our hypothesis is that antioxidant treatments could prevent in a global way virtually all cirrhosis-related complications acting in two crucial levels in the pathophysiological cascade of events: (a) in a primary level, which is the gut-liver axis by ameliorating gut-derived endotoxemia, through prevention of intestinal oxidative stress and its associated gut barrier dysfunction, concurrently conferring direct antioxidant protection in the liver tissue and (b) in a secondary level, which refers to the diverse organs whose function is affected by liver cirrhosis, by preventing their oxidant-related structural and functional derangements.

Pentoxifylline: a first line treatment option for severe alcoholic hepatitis and hepatorenal syndrome?

Although favourable results of pentoxifylline (PTX) used in treatment of severe alcoholic hepatitis patients with a Maddrey discriminant function score > or = 32 have been previously reported, it is not currently recommended as a first line treatment for alcoholic hepatitis owing to lack of evidence for its efficacy as compared to the standard treatment with corticosteroids. In a very recent issue of World Journal of Gastroenterology, Dr. De BK and colleagues compared for the first time the two treatment modalities head to head in a randomized controlled study, demonstrating the advantage of PTX over corticosteroids in terms of patients' survival and risk-benefit profile. The advantage of PTX over corticosteroids in survival of patients with severe alcoholic hepatitis was found to be related to the prevention of hepatorenal syndrome in their study. This study raises the question of the use of PTX as a standard treatment for severe alcoholic hepatitis. Considering the fact that PTX presented a spectacular efficiency in prevention of hepatorenal syndrome in their study as well as that previous studies have shown that this effect is possibly related to a primary renoprotective action because it is irrelevant of tumor necrosis factor-alpha synthesis inhibition or improved liver function, we tempted to speculate that PXT might be an effective option for prevention and/or treatment of hepatorenal syndrome complicating other forms of advanced liver disease. This attractive theory remains to be elucidated by pressing future studies in view of the lack of effective treatment modalities for hepatorenal syndrome.