Safety and Efficacy of Direct-acting Antiviral Therapies for Chronic HCV Infection in Hemodialysis Patients.

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting. PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue. RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance. CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.

New therapeutical indications of ursodeoxycholic acid.

Until the 1980s the role of bile acids in the initiation of liver injury in man was only suspected on the basis of the toxicity of whole bile and bile salts, and of studies showing elevations in serum and tissue levels of bile salts in liver diseases. The beneficial effects of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis have provided the first firm evidence that bile acids may in some way be related to injury in man. There are many questions regarding the hepato-protective effect of UDCA that should be addressed in the near future. In particular, we do not know how chronic cholestasis induces liver fibrosis and if UDCA can prevent or counteract this process. Most cholestatic diseases have an immune pathophysiological basis. We must learn much more about the impact of cholestasis and bile acids on the immune system, particularly on endogenous or exogenous peptide presentation in cells exposed to high concentrations of bile components. We have seen that the trafficking of transporters in hepatocytes may be affected by bile acids; efforts must be made to learn more about this important issue. Finally, structural analogues of UDCA or combinations of drugs should be studied, in order to determine if better therapeutic efficacy could be obtained.

Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease.

UNLABELLED: The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB). AIMS: To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD. METHODS: Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest>0.38 as a surrogate for steatosis >5%), IR (HOMA-IR>2.7 as a surrogate for IR) and fibrosis (FibroTest>0.48 as a surrogate for significant fibrosis, ≥F2). RESULTS: HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p<0.001). The prevalence of steatosis >5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p<0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p<0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p<0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p<0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p<0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p<0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC. CONCLUSIONS: Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis.

Successful application of MARS therapy in a 7 year-old patient with hepatic chronic rejection and severe cholestatic syndrome.

Liver transplant currently represents the therapeutic method for irreversible acute and chronic liver diseases without any other available therapy. In some cases, before or after liver transplantation, it is necessary to replace the functions of the liver. We report the case of a 7 year-old female patient with type I glycogenosis who was transplanted in July 2001 using living-related donor transplantation and who developed chronic rejection two months later. In this case, we used MARS (Molecular Adsorbents Recirculating System) detoxification therapy to optimise the patient's clinical and biological status and to create a bridge that allowed the patient's survival until retransplantation was available. The therapy was well tolerated, with no major incidents. We noted favourable clinical effects and significant improvement in serum bilirubin level, urea nitrogen level and serum creatinine level. We consider that MARS treatment is a temporary solution for patients with acute and acute-on-chronic liver failure, indicated in those cases with real chances of recovery of the hepatic functions or in patients on the liver transplantation waiting list.

A cross-sectional epidemiological study of HBV, HCV, HDV and HEV prevalence in the SubCarpathian and South-Eastern regions of Romania.

AIM: To evaluate the prevalence of HBV, HCV, HDV and HEV infections in populations with different categories of risk and the seroprevalence of HBV and HCV infections in subjects asking for a medical examination. METHOD: We conducted a cross-sectional, epidemiological study in 2,851 subjects from the SubCarpathian and South-Eastern Romania (including 17 counties, 34% of the country area and 42% of the population). The subjects were divided into four groups: controls (n=2,540, i.e. consecutive subjects asking for a medical examination), subjects with very low risk (students; n=44), with low risk (doctors and nurses; n=93) and with high risk for viral hepatitis (hemodialysis patients; n=174). All subjects were screened for HBsAg, antiHCV and ALT level. In populations at risk, antiHBs, HBeAg, antiHBe, antiHBc (IgG), HBV-DNA, HCV-RNA, antiHDV(IgG) and antiHEV(IgG) were also assessed. RESULTS: In controls, HBV seroprevalence was 5.59% and HCV seroprevalence 4.56%. The risk factors for HBV infection were: age, male gender and South-East region of Romania. The risk factors for HCV infection were: age, female gender, elevated ALT level and the South-East region of Romania. In the very low risk population HBV, HCV, HDV and HEV seroprevalence was: 2.27%, 0%, 0% and 12.5%, respectively. In low risk population the seroprevalence was 2.15%, 1.07%, 0% and 13.98%. In hemodialysis patients, HBV and HCV seroprevalence were 7.91%, respectively 39.26%. HCV-RNA was detectable in 20.69% cases. CONCLUSION: In the South and South-Eastern Romania the seroprevalence of viral hepatitis infections is intermediate, similar to other Romanian regions or the Balkans.

Prolonged treatment with interferon alpha and peginterferon induces rheumatoid arthritis syndrome and erythema nodosum.

The antiviral treatment of chronic C hepatitis has improved significantly over the past decade with the introduction of interferons (IFNs), and more recently, pegylated IFNs. Up to two-thirds of all patients treated with pegylated IFN combined with ribavirin can now achieve viral eradication if treated according to current guidelines. Despite this success rate, hematological, immunological, rheumatological and dermatological side effects have been reported in chronic hepatitis C patients treated with IFN-alpha. The subjects of this report are two young females with chronic hepatitis C, who developed rheumatoid syndrome and/or erythema nodosum during antiviral treatment with IFN-alpha or pegylated IFN combined with ribavirin.

The role of cytokines in non-alcoholic steatohepatitis. A review.

The pathogenesis of NASH is being unraveled by studies of animal models and humans with this disorder. The necro-inflammatory component of NASH appears to be modulated by interactions among various factors (for example cytokines, hormones, neurotransmitters) that regulate the biological activity of TNF- and other proinflammatory (Th-1) cytokines. Hepatic necroinflammation is necessary, but not sufficient, for progression to cirrhosis. Factors such as leptin inducible factors (for example, noradrenaline), that regulate the activity of profibrogenic cytokines, such as IL-10 and TGF-beta, dictate the extent of fibrosis that occurs during liver injury. A better understanding of how these and other soluble and cell associated factors regulate the phenotypes of different types of liver cells should help us to develop rationale treatments for NASH and other disorders in the metabolic syndrome.