Metabolic determinants of NAFLD in adults with type 1 diabetes.

AIM: To assess the main metabolic determinants of non-alcoholic fatty liver disease (NAFLD) in adult patients with type 1 diabetes (T1D). METHODS: 115 patients with T1D were divided into 4 groups according to NAFLD grade. NAFLD was diagnosed via transient elastography when CAP > 233 dB/m. Body composition was evaluated by Inbody720, Biospace. Serum lipids, liver enzymes, uric acid, creatinine, hsCRP and HbA1c were evaluated at fasting. RESULTS: The overall prevalence of NAFLD was 47% (n = 54). In the subgroup with BMI > 25 kg/m2 NAFLD prevalence was 66%; and positive family history of type 2 diabetes brought the risk up to 76%. 37% of the lean individuals also had NAFLD. HbA1c > 7% doubled the risk of NAFLD. Waist circumference > 82.5 cm was independently related to NAFLD, accounting for 24% of its variation in females. Accumulation of two and three metabolic syndrome (MetS) components, besides hyperglycemia, increased the risk of NAFLD by 14% (p < 0.0001) and 6% (p = 0.024), respectively. Lean NAFLD correlated with total insulin dose; NAFLD in overweight T1D patients correlated with triglycerides. CONCLUSIONS: NAFLD is highly prevalent in adults with T1D and obesity or other metabolic derangements and might be independently related to poor long-term glycemic control and waist circumference in females.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

A comparison of the pharmacokinetics and safety of enzalutamide in subjects with hepatic impairment and matched healthy subjects.

WHAT IS KNOWN AND OBJECTIVE: Enzalutamide is an androgen receptor inhibitor approved for treatment of metastatic castration-resistant prostate cancer. Enzalutamide is highly protein bound and eliminated primarily by hepatic metabolism; therefore, it is important to understand whether enzalutamide pharmacokinetics is altered by hepatic impairment. METHODS: Pharmacokinetic data were obtained from two non-randomized, open-label, single-dose, phase 1 studies conducted in patients with mild (Child-Pugh class A, n = 6) or moderate (Child-Pugh class B, n = 8) hepatic impairment (NCT01901133) or severe (Child-Pugh class C, n = 8) hepatic impairment (NCT02138162) and their corresponding matched healthy controls; data from both studies are presented here. Subjects with hepatic impairment had liver cirrhosis (n = 19) or chronic hepatitis (n = 3). All subjects received a single oral dose of 160 mg enzalutamide under fasting conditions, with blood samples collected predose and up to 49 days post-dose. RESULTS AND DISCUSSION: Exposure to enzalutamide active moieties, based on the area under the curve of the sum of enzalutamide and N-desmethyl enzalutamide (an active metabolite with similar potency to enzalutamide), increased by 13%, 18% and 4% in subjects with mild, moderate and severe hepatic impairment, respectively, relative to matched controls. Compared with healthy controls, the mean maximum plasma concentration for enzalutamide active moieties was 24% higher in subjects with mild hepatic impairment and 11% and 41% lower in subjects with moderate and severe hepatic impairment, respectively. Enzalutamide was generally well tolerated, with no clinically significant trends in abnormal laboratory findings, vital signs or electrocardiograms. WHAT IS NEW AND CONCLUSIONS: No major differences in single-dose pharmacokinetics were observed in subjects with hepatic impairment vs. matched healthy controls. Therefore, these studies indicate that no initial dose adjustment is necessary when administering enzalutamide to patients with hepatic impairment.

Doppler parameters of hepatic and renal hemodynamics in patients with liver cirrhosis.

Introduction. There are limited studies on simultaneous evaluation of liver and renal blood flow using Doppler methods. We evaluated and compared the changes of liver and renal Doppler US parameters in patients with liver cirrhosis according to the degree of liver disease. Material and Methods. We assessed a large spectrum of liver and renal Doppler US parameters in 67 patients with liver cirrhosis. Results. Significant differences between Child's classes or score, as well as MELD score, were observed in all investigated intrarenal blood flow Doppler US parameters, except renal artery peak systolic velocity, but only in some of the hepatic ones. The deviations of renal Doppler US parameters were also related with the complications of liver cirrhosis, as well as serum urea and creatinine levels. There was relationship between Doppler US parameters of hepatic artery and the corresponding renal artery Doppler US parameters. The changes of Doppler US parameters were age independent. Conclusion. Our results show, renal Doppler US parameters correlate with the severity and complications of liver cirrhosis. Because of dynamic deviations of renal Doppler US parameters with advance of liver cirrhosis, we recommend Doppler US of renal artery as a part of follow up of these patients.

Sodium pyruvate infusions in patients with alcoholic liver disease. Preliminary report.

Pyruvate has been shown to benefit cellular energy metabolism and to reduce free radical formation. Concerning gastrointestinal side effects of orally administered sodium pyruvate, in this pilot study we investigated the therapeutic effectiveness of sodium pyruvate infusions in patients with alcoholic liver disease (ALD). Fifteen patients with ALD received sodium pyruvate infusions for: (1) 10 days (54-86.4 g pyruvate daily, 150-180 mg/min., 6-8 h); and (2) 15 days (50-54 g daily, 100 mg/min., 6 h). Sodium pyruvate treatment resulted in significantly decreased serum AST (p<0.03), ALT (p<0.03), AP (p<0.004), GGT (p<0.05), and total bilirubin (p<0.04). Improvement of liver function was also evident from the significantly decreased Combined Clinical and Laboratory Index (from 6.50+/-0.71, to 3.92+/-0.84, p<0.001), and Liver Damage Score (from 3.83+/-0.71 to 2.75+/-0.58, p<0.01). The two therapy schedules used showed similar results. Unchanged serum pyruvate, lactate, and glucose confirmed the good utilization of pyruvate. Tolerance of sodium pyruvate treatment was very good in 26.09% and good in 68.94% of the observations. Our results showed good therapeutic effectiveness and good tolerance of sodium pyruvate infusions in patients with ALD. This is possibly due to the rapid gain of ATP and GTP, required to redress defective cells, and to antioxidant action of pyruvate.

Quantitative assessment of severity of biliary tract infection.

BACKGROUND/AIMS: It is very important for physicians to evaluate the severity of the biliary infection. At the moment, there is no useful quantitative system. In this study, we propose a scoring system for assessing the severity of biliary infections and evaluation of the efficacy of antibacterial and endoscopic treatments. MATERIALS AND METHODS: We created a biliary tract infection score (BTIS) including local physical and ultrasound findings, signs of inflammation and hepatobiliary involvement. The BTIS was calculated in 317 patients: group I-155 pts with cholecystitis and cholangitis, treated only by antibiotics and group II-162 pts with acute cholangitis treated by endoscopic procedures. RESULTS: The BTIS allowed the differentiation of the severity of biliary infections: 15.50 +/- 0.52 in acute cholangitis group and 5.77 +/- 2.79 in group I (p < 0.001). The BTIS significantly decreased after antibacterial therapy (excluding only the cefotiam subgroup) and in endoscopicaly treated patients. CONCLUSIONS: The BTIS is a combination of simple, reliable, acceptable and low cost parameters, reflecting the principal pathological processes and degree of abnormalities. A BTIS facilitated the assessment of severity of biliary infection and comparison of the results of various methods of treatment.

Clinical meaning of GGT activity in follow-up of patients with alcohol-related liver injury and cholestasis.

The dynamics of GGT was investigated in three groups of patients after removing some primary causes of GGT increase. Group A included 34 patients with alcohol-related liver disease, group B included 16 patients with alcoholic liver injury and cholestasis, caused by concomitant alcoholic pancreatitis and group C included 17 patients with extrahepatic cholestasis, caused by choledocholithiasis. Follow-up assays of GGT were performed on the 7th, 14th and 30th days. Our results showed that the dynamics of GGT was more rapid after removing the cause for cholestasis than in stopping alcohol consumption in patients with chronic liver diseases. On the 14th day more than a 50% decrease in GGT activity was noted in 20% of the patients from groups A and B and in almost all cases from group C. On the 30th day, the reference range of GGT was not attained by any of the patients with liver disease nor in five patients from group C. No significant correlation was found between the severity of liver damage and the extent of GGT increase at the beginning and at the end of the follow-up period.

[The protease inhibitor treatment of the disseminated intravascular coagulation syndrome in patients with liver cirrhosis]. / Lechenie s proteazni inkhibitori na sindroma na diseminirana intravazalna koagulatsiia pri bolni s chernodrobna tsiroza.

The results of the treatment of the syndrome of disseminated intravascular coagulopathy (DIC) in 41 patients with liver cirrhosis are reported. A relation between the severity of the liver impairment and the degree of the increase of the fibrin split products (FSP) was established. FSP above 100 micrograms/ml were found in patients with III class liver failure according to Child-Turcotte-Pugh and rating above 6.5 according to Z. Krustev. The administration of 30,000-60,000 U of the protease inhibitor contrykal led to mastering of the hemorrhagic diathesis in 19 of 21 patients (group A). The increased FSP in the serum fell (chi 2 = 5.79; p less than 0.001). In contrast, the administration of PAMBA and styptanon did not affect the hemorrhagic diathesis and DIC syndrome in 16 of 20 other patients (group B--chi 3 = 20.54; p less than 0.001). The authors recommend protease inhibitors as the treatment of choice of DIC syndrome in liver cirrhosis. Only in case of lack of effect should heparin be added.

[A modified Sugiura operation]. / Vurkhu modifitsiranata operatsiia na Sugiura.

The modified method of Sugiura is reported for the first time in Bulgaria. The operation is less traumatic than the original one, the postoperative case fatality rate is lower, patient survival rate up to 7 years is high and there is no encephalopathy. This operative technique is more practicable than splenorenal anastomosis and may be applied both for planned and for emergency operations. Two patients have been operated by the authors, using the modified technique of Sugiura, with very good results.

[A modified Sugiura operation]. / Vurkhu modifitsiranata operatsiia na Sugiura.

This is the first report in Bulgaria of the application of the modified method of Sugiura. The operation is less traumatic than the original one, the postoperative mortality is essentially reduced, patient survival to 7 years is increased and there is no encephalopathy. This operation is technically easier to perform than splenorectal anastomoses and may be performed both as planned and emergency intervention. Two personal observations on two patients operated by the modified technique of Sugiura are reported. The results were very good.

[Role of hepatitis B virus infection in chronic glomerulonephritis]. / Le rôle de l'infection par le virus de l'hépatite B dans les glomérulonéphrites chroniques.

This study included 60 patients suffering from chronic glomerulonephritis (GN), confirmed by punch biopsy of the kidney. HBs antigen (Ag) was found in the sera of 5 patients, whereas anti-HBs and/or anti-HBc antibodies were found in 3 others. Of the 139 subjects carrying HBsAg or anti-HBc antibodies 117 suffered from chronic liver disease and 3 from chronic GN. Of the 11 patients afflicted with chronic GN and one with a hepatitis B virus (HBV) infection 9 had GN with IgA deposits and the other 2 had membranoproliferative GN. The renal tissue of these 11 patients was examined for the presence of HBs. HBc and HBe antigens using monoclonal antibodies. Virus particles were unsuccessfully sought by electron microscopy. It is possible that, in some patients infected with HBV and afflicted with chronic liver disease, the IgA deposits in the glomeruli result from the perturbed liver metabolism.

[Circadian changes in gastric acidity during drug therapy of duodenal ulcer]. / Denonoshtni izmeneniia na stomashnata kiselinnost pri medikamentoznoto lechenie na duodenalnata iazva.

The circadian change of gastric acidity was studied in 9 patients and 2 controls. Five patients were treated with gastrozepin, two with vicalin and buscolysin, two with biomet according to a schedule. Gastric content was aspirated at fixed intervals and pH determined separately of each portion. The data were juxtaposed to those of the gastric probe prior to the beginning of the treatment. They revealed that with the treatment with gastrozepin and biomet, the lowest pH values during the day were higher, with a statisticall significance, than those obtained at basal conditions prior to the treatment. During the night, pH over 3 was observed only in the treatment with biomet. The methodical conditions used ate suitable both for clinical-pharmacological investigations and for individualization of the treatment of some patients that failed to respond to the ordinary therapeutic combinations.