Hepatitis C virus (HCV) eradication from dialysis facilities in a community using direct acting antivirals (DAAs) may be achieved more effectively under a collaborative care model, including a ...network of hepatologists, nephrologists and specialized dialysis staff. This study aimed to evaluate the prevalence of HCV infection in patients undergoing renal replacement therapy in all registered dialysis units operating in Rio Grande do Sul State (RS), in Southern Brazil. Furthermore, to implement a strategy to treat HCV infection locally at these units.
All dialysis units in RS State were contacted between January 2020 and January 2022 to provide results of anti-HCV screening in dialysis patients. Those with positive results were discussed via telemedicine with a team of two hepatologists and one nephrologist located in Clinics Hospital of Porto Alegre, a tertiary health care facility. Dialysis staff was instructed to test HCV RNA with polymerase chain reaction (PCR) and calculate FIB-4 and APRI scores. Viremic patients were selected for therapy and those with FIB-4 >3.25 and/or APRI >1.5 were required to undergo ultrasonography and/or elastography. DAA therapy was started locally by the dialysis unit staff under the supervision of the hepatologists.
A total of 6,991 patients from all 66 dialysis facilities in RS State were enrolled. Most patients (93.3%) were on hemodialysis. All patients completed HCV screening and 454 (6.5%) were anti-HCV positive. So far, nine units have completed the proposed model, with 89 anti-HCV positive patients that resulted in 49 (55.5%) with detectable HCV RNA by PCR. All viremic patients started HCV therapy. Interim analysis showed SVR in 21 (95.5%) of 22 patients.
A collaborative care model increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization towards HCV elimination up to 2030.
The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved ...glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy.
Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control.
The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range IQR 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years.
Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.
Sustained virological response (SVR) of hepatitis C virus (HCV) with direct acting antivirals (DAAs) improve survival and reduces progression to cirrhosis, decompensation and hepatocellular ...carcinoma. Glucose metabolism impairment is one of the most frequent extra-hepatic manifestations of chronic HCV infection. The impact of SVR on glycemic parameters and baseline variables associated with this outcome remains uncertain. This study aimed to evaluate glucose metabolism before and after SVR, as well as investigate the presence of baseline characteristics related to improvement in glycemic control.
Prospective study of chronic HCV infection patients treated with DAAs between January 2016 and December 2017 at Viral Hepatitis Outpatient Clinic of Hospital de Clinicas de Porto Alegre, Brazil. Inclusion criteria were SVR to DAA therapy with follow-up for at least 24 weeks after the end of therapy. The exclusion criteria were the presence of other etiology of liver disease. Glycated hemoglobin (A1C) was analyzed before and after treatment in all patients. Subgroups were stratified by cirrhosis, genotype, BMI, age and presence or absence of baseline glycemic disorder. The primary outcome was a change in glycemic homeostasis after HCV eradication without a change in pharmacologic therapy with an impact on glycemic control. Secondary outcomes were baseline variables associated with improvement of glucose control.
A total of 207 patients were included, with a mean age of 60.6±10.7 years. Forty-eight percent were males. Cirrhosis was found in 56% and genotype 3 in 37% of patients. T2DM or PD at baseline was present in 54.5%. Overall, median A1C at baseline reduced significantly after SVR (5.7, IQR 5.3-6.7 to 5.5, IQR 4.9-6.3, respectively, p=0.01). Baseline characteristics associated with statistically significant improvement in glycemic control after SVR were cirrhosis, genotype 3 and age below 60 years old.
SVR with DAAs was associated with improved glycemic control, particularly among patients with cirrhosis, genotype 3 and/or age below 60 years old.
Hepatitis C (HCV) is a systemic disease with hepatic and extrahepatic repercussions, its association with some diseases, such as hepatocellular carcinoma is well documented, however its relationship ...with glucose metabolism is still unclear. Objective: to analyze the impact of the sustained viral response (SVR) on the glucose metabolism in patients with HCV, before and after 12 weeks of treatment with direct acting antivirals (DAA).
207 HCV patients attended at the Outpatient Clinic for Viral Hepatitis of the Hospital de Clínicas de Porto Alegre, from October 2015 to December 2018, participated in the study. Participants who obtained SVR and had data on glucose metabolism (fasting glucose and/or HbA1c) were included before and after the treatment.
Of the 207 participants, 52% (107) were women. Type 2 diabetics (DMT2) and pre-diabetics had a higher frequency of comorbidities and polypharmacy, compared to the normoglycemic ones. Regarding blood glucose classification, 98 (47%) were normoglycemic, 58 (28%) pre-diabetic and 51 (25%) diabetics at the beginning of treatment. After the treatment, 17/98 (17.3%) normoglycemic patients came to be pre-diabetic and none were diagnosed with T2DM. Among the pre-diabetics, 11/58 (18.9%) went to DMT2 and 29/58 (50%) returned to being normoglycemic. As for pre-treatment DMT2 patients, 12/51 (23.5%) returned to pre-diabetes, while 3/51 (5.9%) became normoglycemic.
Most patients who achieve SVR after treatment with DAA show improvement or stability of the glycemic parameters, including among those already diagnosed with DMT2. However, a subgroup shows worsening of glucose metabolism, including progression to diabetes.
Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease ...(NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.
Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease ...(NAFLD).
The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis.
HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH.
A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%).
Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.
A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a ...(Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection.
Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR.
A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm.
In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.
The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of ...hepatitis C is historically challenging. The purpose of the current study was to assess (in a ‘real-life’ setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV.
We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities.
Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvir-based regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four drop-outs obtained SVR.
All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a ‘real–life’ clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way.
With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data ...regarding prognostic survival factors are of significant importance.
A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI).
Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality HR 3.22 (CI 1.64;6.33); P<.001. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation HR 2.9 (1.64;5.29); P<.0001, and symptomatic progression HR 3.9 (1.53;9.78); P=0.004 were independently associated with mortality after first-line systemic treatment discontinuation.
The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.
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