Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus.

BACKGROUND: The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM: To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS: A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS: Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naïve group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION: The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.

Feasibility of self-propelling nasojejunal feeding tube in patients with acute pancreatitis.

BACKGROUND & AIMS: To assess the success rate of a self-propelling nasojejunal feeding tube in patients with acute pancreatitis. METHODS: All patients admitted for acute pancreatitis were included. A self-propelling nasojejunal feeding tube was introduced into the stomach, and gastrointestinal motility was stimulated using metoclopramide. If the tube failed to advance to the ligament of Treitz, a nasojejunal tube was placed endoscopically. RESULTS: A total of 108 patients, 94 with necrotizing pancreatitis (Balthazar D/E) and 14 with nonnecrotizing pancreatitis (Balthazar B/C), were referred for artificial nutrition. In 11 cases, ileus persisted and parenteral nutrition was initiated. Among the remaining 97 patients, 5 refused tube placement. The self-propelling feeding tube was inserted in 92 patients with successful migration to the ligament of Treitz in 61% (n = 56) and failure in 39% (n = 36). Of the 36 patients with an initial failed placement, endoscopic placement of a nasojejunal tube was successful 80% of the time (29 patients). The success rate of a nasojejunal self-propelling feeding tube placement correlated directly with the severity of the acute pancreatitis (92% in B/C vs 61% in D vs 48% in E; P < .05). CONCLUSIONS: Use of a self-propelling nasojejunal tube is a simple technique that can be successfully performed in the majority of patients with acute pancreatitis. The utility of this procedure in the most severe cases of acute pancreatitis continues to pose a challenge.

Long term highly saturated fat diet does not induce NASH in Wistar rats.

BACKGROUND: Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. METHODS: 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. RESULTS: MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25-28% vs standard). CONCLUSION: Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH.

Actigraphy: A new diagnostic tool for hepatic encephalopathy.

AIM: To assess the actigraphy, an ambulatory and continuous monitoring of wrist motor activity fitted to study sleep/wake patterns in hepatic encephalopathy (HE). METHODS: Twenty-five cirrhotic patients (17 M, 8 F, mean age 56+/-11 years, 24/25 alcoholic, Child-Pugh A , B, C: 2, 6, 17) were included. The patients were classified into 3 groups: stage 0 group (n = 12), stage 1-2 group (n = 6), and stage 3-4 group (n = 7) of encephalopathy. Over three consecutive days, patients had clinical evaluation 3 times a day with psychometric test, venous ammoniemia, flash visually evoked potentials (VEP), electroencephalogram and continuous actigraphic monitoring for 3 d, providing 5 parameters: mesor, amplitude, acrophase, mean duration of activity (MDAI) and inactivity (MDII) intervals. RESULTS: Serum ammonia and VEP did not differ among the 3 groups. Electroencephalography mean dominant frequency (MDF) correlated significantly with clinical stages of HE (r = 0.65, P = 0.003). The best correlation with HE stage was provided by actigraphy especially with MDAI (r = 0.7, P < 10(-4)) and mesor (r = 0.65, P < 10(-4)). MDAI correlated significantly with MDF (r = 0.62, 0.004) and was significantly shorter in case of HE compared to patients without HE (stage 0: 5.33+/-1.6 min; stage 1-2: 3.28+/-1.4 min; stage 3-4: 2.52+/-1.1 min; P < 0.05). Using a threshold of MDAI of less than 4.9 min, sensitivity, specificity, positive predictive value, negative predictive value for HE diagnosis were 85%, 67%, 73% and 80%, respectively. CONCLUSION: Actigraphy may be an objective method to identify HE, especially for early HE detection. Motor activity at the wrist correlates well with clinical stages of HE. MDAI and mesor are the most relevant parameters.

Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea.

Despite an ancient reputation for potential phytotherapeutic effects and innocuity, traditional herbal medicine has previously been implicated in severe adverse events. Exolise is an 80% ethanolic dry extract of green tea (Camellia sinensis) standardized at 25% catechins expressed as epigallocatechin gallate, containing 5-10% caffeine. It has been available in France, Belgium, Spain and the United Kingdom since 1999, as an adjuvant therapy for use in weight loss programmes. In various studies, green tea has to date been considered useful for its potential hepatic protective properties. In this study, we report a case of fulminant hepatitis during self-medication with Exolise, requiring liver transplantation.

Polyunsaturated fatty acid deficiency reverses effects of alcohol on mitochondrial energy metabolism.

BACKGROUND/AIMS: Polyunsaturated fatty acids (PUFA) deficiency is common in patients with alcoholic liver disease. The suitability of reversing such deficiency remains controversial. The aim was to investigate the role played by PUFA deficiency in the occurrence of alcohol-related mitochondrial dysfunction. METHODS: Wistar rats were fed either a control diet with or without alcohol (control and ethanol groups) or a PUFA deficient diet with or without alcohol (PUFA deficient and PUFA deficient+ethanol groups). After 6 weeks, liver mitochondria were isolated for energetic studies and fatty acid analysis. RESULTS: Mitochondria from ethanol fed rats showed a dramatic decrease in oxygen consumption rates and in cytochrome oxidase activity. PUFA deficiency showed an opposite picture. PUFA deficient+ethanol group roughly reach control values, regarding cytochrome oxidase activity and respiratory rates. The relationship between ATP synthesis and respiratory rate was shifted to the left in ethanol group and to the right in PUFA-deficient group. The plots of control and PUFA deficient+ethanol groups were overlapping. Phospholipid arachidonic over linoleic ratio closely correlated to cytochrome oxidase and oxygen uptake. CONCLUSIONS: PUFA deficiency reverses alcohol-related mitochondrial dysfunction via an increase in phospholipid arachidonic over linoleic ratio, which raises cytochrome oxidase activity. Such deficiency may be an adaptive mechanism.

Cardiac sources of embolism should be routinely screened in ischemic colitis.

OBJECTIVE: Potential cardiac sources of embolism may promote ischemic colitis. The aim of this study was to evaluate their role in segmental, nongangrenous ischemic colitis and to determine the usefulness of routine cardiac evaluation in patients with this disease. METHODS: Sixty case and 60 control patients matched for age and gender were included and questioned regarding treatment and prior cardiovascular history or risk factors. Potential cardiac sources of embolism, classified as "proven" or " still debated," were screened using an electrocardiogram, rhythmic Holter monitoring over 24 h, and transthoracic echocardiography. RESULTS: Sex ratio (male:female) was 1:2, and mean age was 70 +/- 14 yr. Case and control patients had similar drug use, prior cardiovascular history, and risk factors. A potential cardiac source of embolism was found in 26/60 case (43%), compared with 14/60 control patients (23%) (p = 0.02; OR = 2.5, 95% CI = 1.2-5.5). Excluding the "still debated," 21/60 case (35%), compared with 8/60 control patients (13%), had a "proven" cardiac source of embolism (p < 0.01; OR = 3.5, 95% CI = 1.4-8.4). Electrocardiogram alone misdiagnosed 72% of the "proven" cardiac sources of embolism, whereas the combination electrocardiogram plus Holter monitoring detected 71%, and electrocardiogram plus echocardiography 62%. Twelve of 21 case patients with at least one proven cardiac source of embolism, were previously unknown. Anticoagulant therapy was required in 32% of case patients and antiarrhythmic therapy in 25% of cases. CONCLUSIONS: Potential cardiac sources of embolism were more common in patients with segmental, nongangrenous ischemic colitis than in control patients. Therefore, these patients should undergo a routine electrocardiogram, rhythmic Holter monitoring, and transthoracic echocardiography. Anticoagulant therapy should also be considered for this patient population.