Tenofovir alafenamide prophylaxis post-liver transplantation: a real-world study in patients with chronic kidney disease.

Background & aims: Tenofovir alafenamide fumarate (TAF) was shown equally efficacious in suppressing hepatitis B virus (HBV) but with less renal toxicity than tenofovir disoproxil fumarate (TDF). The aim of this real-world study was to evaluate renal function in post-liver transplantation (LT) patients that changed TDF with TAF. Methods: The TAF group (n=17) included patients who switched to TAF due to low (<60 ml/min/1.73m2) Glomerular Filtration Rate (GFR). The control group included patients that remained on TDF (n=30), although some (n= 14) had chronic kidney disease (CKD) (TDF-CKD group). GFR was assessed using: i) MDRD-6 variable; ii) CKD-EPI formula; iii) radionuclide technique (rGFR). Results: There were no significant differences between the two groups except for the presence of diabetes and follow-up period, which were more common and shorter, respectively, in the TAF group (35% vs. 10%, p=0.03; 13.7 vs. 35.5 months, p<0.001). At the end of follow-up there were no significant changes in renal function between the TAF and the TDF group or TDF-CKD group, although the numerical change in rGFR in the latter comparison was greater in the TAF group (ΔrGFR 3 vs. -2.14 ml/min, p=0.26). The use of everolimus was associated with improvement in renal function (ΔrGFR 2 vs. -7.75 ml/min, p=0.06 [TAF vs. TDF group]; 2 vs. -12 ml/min, p=0.01 [TAF vs. TDF-CKD group]). There were no TAF- related side effects or cases of HBV recurrence. Conclusion: Conversion to TAF in post-LT patients who develop CKD does not lead to improvement of kidney function after a period of one year.

'Distribution of Hepatitis C Virus genotypes in northern Greece in the last decade: descriptive analysis and clinical correlations'.

Hepatitis C virus (HCV) represents a major public health problem, while the identification of a HCV genotype is clinically very important for therapy prescription. The aim of the present study was to determine the HCV genotype distribution patients from northern Greece with HCV RNA positive viral load and to identify whether there is a shift in this distribution, during 2009-2017. The study was performed on 915 HCV positive patients and according to the results, genotype 3 was the most prevalent genotype (Ν = 395, 43.2%) followed by genotype 1 (Ν = 361, 39.5%). Regarding the gender of the patients, genotype 1 was mostly detected in women. Moreover, genotype 1 was associated with higher viral loads, while genotype 3 was most frequently detected in patients with a history of intravenous drug use. In conclusion, our results show that genotype 3 is the most prevalent genotype in Greece during the last decade as opposed to older epidemiological studies, likely due to intravenous drug use becoming the major source of infection.

Virologic response and resistance to lamivudine in patients with chronic hepatitis B: a ten-year retrospective analysis.

BACKGROUND: Emergence of resistance was recognized shortly after the introduction of lamivudine. This 10 year retrospective study investigates resistance to lamivudine and the modifications of antiviral strategies required. PATIENTS AND METHODS: Two hundred and nine patients were treated with lamivudine. Sixty seven out of 209 patients were excluded from the present study. HBVDNA was tested using the PCR assay and genotypic resistance was performed using the direct PCR sequencing. RESULTS: In the 125 patients initially treated with lamivudine monotherapy: Α) 48 (38.4%) patients with a mean time of 63.6±26.2 months under lamivudine treatment have normal ALT levels with negative (19%) or low (<1X102) HBVDNA levels, 10% developed cirrhosis, 1 HCC and 6% cleared HBsAg. Β) Resistance was developed in 61.60% patients within 45±23.84 months of lamivudine treatment. These patients were: 1) either switched to adefovir (9), entecavir (2) or tenofovir (2) or adefovir was added to lamivudine (21) for a short time and then they were switched to adefovir alone. Six out of 34 patients developed cirrhosis and 4 HCC while on treatment. 2) or adefovir was added-on to lamivudine (43). In 39 out of 43 treatment is ongoing while on virological response. No one developed cirrhosis or HCC. C) Seventeen patients received de novo combination therapy with lamivudine and adefovir and 2 out of 17 (11.7%) showed resistance to adefovir after 24 months of therapy. CONCLUSIONS: Our results showed that a) approximately 38.4% of patients maintain viral suppression more than 5 years of lamivudine treatment and b) rescue therapy with add-on adefovir to ongoing lamivudine, seems to be a better treatment strategy associated with long term benefit regarding disease complications.

The clinical presentation of Von Meyenburg complexes.

Von Meyenburg Complexes (VMCs) is a rare clinicopathologic entity, consisting of small (<1.5cm), usually multiple and nodular cystic lesions. VMCs typically cause no symptoms or disturbances in liver function and thus in most instances they are diagnosed incidentally. We present four VMCs cases, each with a distinct clinical presentation. In two of our cases, VMCs caused mild, non-specific abdominal symptoms, including diffuse abdominal pain and discomfort. In the other two cases, in a 60-year-old woman and a 25-year-old man, the clinical presentation was implicative of an infectious hepatic process reminiscent of cholangitis and liver abscesses respectively. In each case the diagnosis was based on magnetic resonance imaging and magnetic resonance cholangiopancreatography findings showing multiple hyper-intense cystic nodules not communicating with the biliary tree. Physicians should be aware of the entire clinical spectrum of VMCs and its unique radiologic features in order to differentiate VMCs from other cystic liver lesions.

High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis.

BACKGROUND: Ursodeoxycholic acid (UDCA) in a dose of 28-30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. AIM: To compare the risk of adverse clinical endpoints in patients with varying disease status. METHODS: We reviewed records from patients previously enrolled in a study evaluating the effects of high dose (28-30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histological stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, oesophageal varices and cholangiocarcinoma was sought. RESULTS: A total of 150 patients were included of whom 49 patients developed endpoints. There was an increased development of endpoints among patients using UDCA vs. placebo (14 vs. 4, P=0.0151) with early histological disease (stage 1-2, n=88) but not with late stage (stage 3-4, n=62) disease (17 vs. 14, P=0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, P=0.0008) with normal bilirubin levels (total bilirubin ≤1.0 mg/dL) but not in patients with elevated bilirubin levels (15 vs. 16, P=0.6018). Among patients not reaching endpoints 31.7% had normalisation of their alkaline phosphatase levels when compared to 14.3% in patients who reached endpoints (P=0.073). CONCLUSION: The increased risk of adverse events with UDCA treatment when compared with placebo is only apparent in patients with early histological stage disease or normal total bilirubin.

Health-related quality of life in Greek chronic hepatitis C patients during pegylated interferon and ribavirin treatment.

UNLABELLED: Background - Aims: Chronic hepatitis C (CHC) can cause a series of neuropsychiatric symptoms, whereas the currently approved treatment for this disease often induces similar symptoms as well. The aim of the present study was to compare Greek CHC patients' health-related quality of life (HRQoL) with that of healthy controls, to identify any possible relationships between HRQoL and demographic and laboratory parameters and to study the fluctuation of HRQoL during therapy and follow-up. PATIENTS AND METHODS: Ninty nine patients with CHC and 91 healthy controls were enrolled in the study. ALT, viral load, HCV genotype, fibrosis stage by liver biopsy and BMI, were determined at baseline. All patients completed the SF-36 quality of life questionnaire, which was self-administered, before treatment. They were treated with pegylated interferon alpha2-a or alpha-2b and ribavirin for 24 or 48 weeks and evaluated in the middle of therapy, at the end and six months after treatment cessation. SF-36 questionnaire was also completed in each evaluation. RESULTS: Patients' HRQoL was found to be below that of healthy controls in all SF-36 scales before treatment. There was a significant negative association between history of drug abuse and general health and a positive association between age and mental health. Multivariate analysis revealed that history of drug abuse seemed to play a significant role in bodily pain and general health of patients, as well as age did in vitality and mental health. The course of patients' HRQoL showed that in the middle of treatment values in all SF-36 scales were below those of baseline and they returned to pretreatment levels at the end of therapy. However, at the end of the six month follow-up period, an improvement in almost all scales compared to baseline was noted. CONCLUSION: Our results showed that a) Greek CHC patients' HRQoL was worse than that of healthy individuals and fluctuated significantly during treatment b) A history of drug abuse and age can independently affect HRQoL c) During treatment values of HRQoL are worsened possibly due to interferon-a treatment and d) In the long-term treatment results in improvement of HRQoL.

Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1-TH2 cytokine profile in subjects with self-limited disease.

Many determinants of the immune response have been implied in the pathogenesis of chronic hepatitis C. TH1 and TH2 cytokines play a prominent role in viral infections and a dysregulation of these cytokines could account for viral persistence and evolution of chronic disease. To explore a possible TH1 and TH2 cytokine dysregulation resulting in the inability to terminate hepatitis C virus (HCV) infection, we studied TH1 [interferon (IFN)-gamma, interleukin (IL)-2] and TH2 (IL-4, IL-10) mRNA expression of peripheral blood mononuclear cells (PBMC) in response to NS3 HCV antigen stimulation, in 31 untreated patients with chronic hepatitis C and 29 subjects with self-limited disease. After a 48 h culture of PBMC, total RNA isolation was performed and complementary DNA was prepared by reverse transcription. mRNA levels were quantified by real-time polymerase chain reaction using a standard curve formed after cloning each cytokine gene and a reference gene using recombinant DNA technology in a specific plasmid vector. In the patients group, mRNA expression of IFN-gamma, IL-2 and IL-4 but not IL-10 was detected, IFN-gamma being the predominant cytokine expressed. All four cytokines were expressed in subjects with self limited disease, however levels of IFN-gamma were lower and a significant higher expression of IL-10 compared to patients was found. There was a significant correlation between IFN-gamma mRNA expression levels and stage of fibrosis. Our findings show that in chronic hepatitis C, TH1 cytokines predominate and correlate to liver immunopathology. Furthermore, subjects with self-limited disease, maintain the ability to respond to HCV antigens for a long time after disease resolution.

Treatment of intravenous drug users with chronic hepatitis C: treatment response, compliance and side effects.

BACKGROUND: Although intravenous drug users (IVDUs) comprise the majority of patients with chronic hepatitis C, most of them are excluded from treatment because of concerns about adherence to treatment and side effects. MATERIAL AND METHODS: In this study we retrospectively evaluated safety, compliance to treatment and efficacy of treatment in IVDUs with HCV infection in 163 former IVDUs with chronic hepatitis C, who were not in methadone substitution and were attending our clinics the period 1997-2004. All subjects were HCVRNA (+), had ALT levels>x1.5 UNL and were treated for their HCV infection. Treatment consisted of three different regimens: IFN-alpha monotherapy (39.8%), IFN-alpha/ribavirin combination therapy (30.1%) and pegylated IFN-alpha/ribavirin combination therapy. RESULTS: Eighty seven over 163 patients (53.3%) discontinued treatment early due to drug abuse relapse (62%), side effects (32.1%, 10% psychiatric) and 5,7% for other reasons. Eighty precent of those who discontinued treatment had pre-treatment drug abstinence/= 9 months.