Use Of Direct-acting Antiviral Agents Research Articles

Direct-acting antiviral agents (DAA) in the management of hepatitis C in a clinical setting: Effectiveness and limitations

Hepatitis C virus (HCV) significantly burdens public healthcare resources and has infected over 73 million people as of 2023. Past treatments for hepatitis C virus relied on ribavirin pegylated interferon. However, this treatment has adverse side effects, such as depression, anemia, etc. At the same time, this method has a low cure rate and poor patient compliance. DAA can not only treat CHC and even cirrhosis, but also play a crucial role in mediating the recovery of immune damage and regulating glucose metabolism in infected patients. In the contemporary approach of HCV, Direct-acting antiviral agents (DAA) resulted in up to 90% cure rates. At the same time, clinical trials showed DAA also provides many benefits to patients during treatment. Still, with the widespread use of DAA, some DAA limitations have also been identified during its use. This article summarizes the benefits and limitations that DAA has demonstrated in the current treatment of HCV.

Shifting perspectives in liver diseases after kidney transplantation.

Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis. The causes are diverse and mainly associated with hepatotropic viruses, drug toxicity and metabolic disorders. Over the past decade, the aetiology of liver disease in kidney recipients has changed significantly. These relates to the use of direct-acting antiviral agents against hepatitis C virus, the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity. In addition, the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients. This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.

Hepatobiliary Impairments in Patients with Inflammatory Bowel Diseases: The Current Approach

Inflammatory bowel disease (IBD) refers to chronic conditions with a low mortality but high disability. The multisystemic nature of these diseases can explain the appearance of some extraintestinal manifestations, including liver damage. Abnormal liver biochemical tests can be identified in approximately one third of patients with IBD and chronic liver disease in 5% of them. Among the liver diseases associated with IBD are primary sclerosing cholangitis, cholelithiasis, fatty liver disease, hepatic amyloidosis, granulomatous hepatitis, drug-induced liver injury, venous thromboembolism, primary biliary cholangitis, IgG4-related cholangiopathy, autoimmune hepatitis, liver abscesses or the reactivation of viral hepatitis. The most common disease is primary sclerosing cholangitis, a condition diagnosed especially in patients with ulcerative colitis. The progress registered in recent years in the therapeutic management of IBD has not eliminated the risk of drug-induced liver disease. Additionally, the immunosuppression encountered in these patients increases the risk of opportunistic infections, including the reactivation of viral hepatitis. Currently, one of the concerns consists of establishing an efficiency and safety profile of the use of direct-acting antiviral agents (DAA) among patients with hepatitis C and IBD. Early diagnosis and optimal treatment of liver complications can improve the prognoses of these patients.

Direct-acting antiviral agent use and gastrointestinal safety in patients with chronic hepatitis C: a pharmacovigilance study based on FDAAdverse Event Reporting System.

Gastrointestinal adverse drug reactions (GADRs) of direct-acting antiviral agents (DAAs) in patients with chronic hepatitis C are underestimated. This study aimed to comprehensively evaluate the gastrointestinal safety of DAAs in patients with chronic hepatitis C. The US FDA Adverse Event Reporting System database was searched for GADR cases reported from 01 to 2012 to 30 September 2021. Twelve DAA types used for hepatitis C virus were included. The top 30 GADRs were assessed based on the use of DAAs, number of cases, and clinical features. A case-non-case disproportionality approach was used to confirm pharmacovigilance signals, whereby reporting odds ratios (ROR) with 95% CI were calculated. Nausea (70.01/1000), diarrhoea (39.10/1000), and vomiting (31.68/1000) accounted for the highest number of cases. The pooled median time-to-onset of the top 30 GADRs was 13 days (Q1-Q3: 2-38) and the proportion of drug discontinuation was 19.17%. The highest number of DAA-related cases involved ledipasvir/sofosbuvir (21.86%), sofosbuvir/velpatasvir (21.77%), and sofosbuvir (13.41%). When DAAs were considered as a class drug, after adjusting for age, sex, concomitant diseases and drugs that potentially induced GADRs, significant RORs for specific GADRs were noted, including abdominal discomfort (1.62, 95% CI 1.32-1.99), constipation (1.54, 95% CI 1.26-1.89), dyspepsia (1.25, 95% CI 1.01-1.55), abdominal distension (1.36, 95% CI 1.05-1.75), faeces discoloured (1.77, 95% CI 1.15-2.73), and gastric ulcer (2.37, 95% CI 1.28-4.41). Clinicians should have a deeper understanding of GADRs to improve the gastrointestinal tolerance of patients with chronic hepatitis C.

Hypoglycemia associated with direct-acting anti-hepatitis C virus drugs: An epidemiologic surveillance study of the FDA adverse event reporting system (FAERS).

Hypoglycemia induced by direct-acting antiviral agents (DAAs) for chronic hepatitis C virus (HCV) infection is a rare but potentially life-threatening adverse reaction, which led to warnings by competent authorities. We therefore aimed to examine the hypoglycemic safety signal for DAAs. Reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 1 October 2012 to 31 March 2020 were analyzed. The Medical Dictionary for Regulatory Activities was used to identify hypoglycemia cases. A case by non-case disproportionality approach was used whereby reporting odds ratio (ROR) with 95% confidence intervals (CI) were calculated. In HCV infection with diabetes patients, the cumulative frequency of hypoglycemic ADRs was 21.85/1000 for reports involving DAAs versus 13.50/1000 for reports involving other medications; For DAAs as a class drug, a nearly double increased reporting odds for hypoglycemia was observed (ROR: 1.63, 95% CI: 1.11-2.41). However, in DAAs subgroup analysis, only telaprevir (ROR: 1.66, 95% CI: 1.01-2.74) and elbasvir/grazoprevir (ROR: 2.25, 95% CI: 1.05-4.83) were associated with increased reporting risk of hypoglycemia during corresponding marketing period; when combined with insulins and sulfonylureas, DAAs were associated with increased reporting risk for hypoglycemia (ROR: 1.98, 95% CI: 1.36-2.88; ROR: 1.62, 95% CI: 1.06-2.48), but concomitant biguanides, dipeptidyl peptidase IV (DPP-4) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1RAs) were not significant. This study supports the current recommendation for cautious about hypoglycemic risk relating to the use of DAAs. Treatment with DAAs and antidabetic agents (especially insulins and sulfonylureas) will increase hypoglycemia reporting risk. Physicians and pharmacists should be aware of this risk when prescribing DAAs for patients suffering from diabetes, advanced age or liver decompensation.

S2591 Hepatitis C-Induced Hepatocellular Carcinoma and Direct-Acting Antivirals

Introduction: Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC). Early cure with direct-acting antiviral agents (DAAs) reduces the risk of progression to HCC and reverses the severity of fibrosis. However, there has been ongoing debate regarding whether or not the use of DAAs causes an increased risk of HCC development after achieving sustained virological response (SVR) compared to patients who do not achieve SVR. This case adds to the debate about DAAs contributing to the occurrence/ progression of HCC in patients with HCV despite achieving SVR. Case Description/Methods: A 55-year-old man with history of alcohol abuse, HCV and decompensated liver cirrhosis presented for initiation of HCV treatment. The patient endorsed 20-pound unintentional weight loss. Ultrasound (US) of the abdomen revealed hepatosplenomegaly and large abdominal ascites without any hepatic lesions (Figure 1). Alpha fetoprotein (AFP) level was 5.7 ng/mL and HCV RNA load was 25,313 IU/mL. After completion of Sofosbuvir/Velpatasvir 400-100 mg daily for 24 weeks, HCV RNA load was undetectable but AFP level was 11,728 ng/mL and abdominal US showed three solid lesions with increased vascularity (Figure 2) concerning for de novo HCC occurrence versus accelerated development of occult HCC despite achieving SVR. Triple phase CT scan of the abdomen confirmed the presence of HCC, and a right portal vein tumor thrombus (Figure 3). The patient was a poor surgical/transarterial chemoembolization candidate and relocated to another state to continue his care. Discussion: Untreated HCV poses a huge morbidity and mortality burden due to its risk of progression to HCC. The advent of DAAs has made HCV treatment available to larger patient population. Earlier literature supported the increased risk of HCC in patients with HCV who were treated with DAAs. Following this, a large French study refuted the increased risk of recurrence rate of HCV-related HCC after DAAs. However, more studies are needed, especially in decompensated patients, to extrapolate data regarding the incidence of de novo HCV-related HCC in patients who received DAA therapy and achieve SVR compared to those who did not achieve SVR. In our case, the possibility of occult HCC prior to HCV treatment cannot be ignored, but did DAAs make it more aggressive? Cases like this necessitate further research about this controversial topic especially in patients with decompensated cirrhosis and possible occult HCC at presentation.Figure 1.: US Image Of The Liver Prior To Initiation of Direct-Acting Antiviral Agents. 2: US Image of Solid Heterogenous Hepatic Lesion. 3. CT Abdomen/Pelvis with Heterogenous Enhancement in the Right Lobe of the Liver.

Attitude and Practices Regarding Use of Direct Acting Antiviral Agents (DAAs) in the Treatment of Hepatitis C among Health Care Practitioners “A Survey-based Study”

Approximately 3% of the world population has been known to be infected with HCV. Hepatitis C virus is a major etiological factor behind the development of liver diseases such as cirrhosis and hepatocellular carcinoma. Interferon-based therapy has remained as the mainstay treatment for HCV for decades. Owing to the unavoidable side effects of interferon, direct-acting antivirals (DAAs) have been approved recently for the treatment of HCV-infected patient. These drugs have brought revolution in the management of HCV because of their favorable side effects profiles and enhanced rates of sustained virological response. We conducted a questionnaire-based survey study to assess the knowledge and current practices among specialists and senior post graduate trainees regarding treatment of HCV with DAAs. The questionnaire was based on latest WHO guidelines for treating HCV. The results obtained were collected and tabulated. Majority (95%) of physicians were between the age of 21-30 years and mostly (69.6%) were females. Almost three fourth of the practitioners were aware of direct-acting antiviral agents (DAAs) and 70.2% agreed that they reduce the duration of treatment along with low bill burden along with lesser side effects. In this study, we could see that the participants’ knowledge and practices regarding use of DAAs, preference over interferon therapy and recommended combinations for different age groups was appreciable, however there is still a gap of knowledge among doctors regarding treatment of HCV with DAAs which needs to be filled with the help of proper health educational programs and training.

Updated View on Kidney Transplant from HCV-Infected Donors and DAAs.

Background: The discrepancy between the number of potential available kidneys and the number of patients listed for kidney transplant continues to widen all over the world. The transplant of kidneys from hepatitis C virus (HCV)-infected donors into HCV naïve recipients has grown recently because of persistent kidney shortage and the availability of direct-acting antiviral agents. This strategy has the potential to reduce both waiting times for transplant and the risk of mortality in dialysis. Aim: We made an extensive review of the scientific literature in order to review the efficacy and safety of kidney transplant from HCV-viremic donors into HCV naïve recipients who received early antiviral therapy with direct-acting antiviral agents (DAAs). Results: Evidence has been rapidly accumulated on this topic and some reports have been published (n = 11 studies, n = 201 patients) over the last three years. Various combinations of DAAs were administered—elbasvir/grazoprevir (n = 38), glecaprevir/pibrentasvir (n = 110), and sofosbuvir-based regimens (n = 53). DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT. The sustained virological response (SVR) rate was between 97.5% and 100%. A few severe adverse events (SAEs) were noted including fibrosing cholestatic hepatitis (n = 3), raised serum aminotransferase levels (n = 11), and acute rejection (n = 7). It remains unclear whether the AEs were related to the transmission of HCV, the use of DAAs, or kidney transplant per se. It appears that the frequency of AEs was greater in those studies where DAAs were not given in the very early post-kidney transplant phase. Conclusions: The evidence gathered to date encourages the expansion of the kidney donor pool with the adoption of HCV-infected donor organs. We suggest that kidney transplants from HCV-viremic kidneys into HCV-uninfected recipients should be made in the context of research protocols. Many of the studies reported above were externally funded and we need research generating “real-world” evidence. The recent availability of pangenotypic combinations of DAAs, which can be given even in patients with eGFR < 30/min/1.73 m2, will promote the notion that HCV-viremic donors are a significant resource for kidney transplant.

Effectiveness of retreatment with ombitasvir/paritaprevir/ritonavir anddasabuvir+sofosbuvir+ribavirin in patients with chronic hepatitis C, subtype 1b, and cirrhosis, who failed previoustreatment with first- and second-generation NS5A inhibitors.

The use of direct-acting antiviral agents (DAAs) in patients with chronic HCV genotype (GT) 1 infection results in sustained virologic response (SVR) rates of 95%-97%, but 3%-5% of patients experience virologic failure. We observed 41 patients infected with HCV subtype 1b who failed previous treatment with DAAs, including 37 subjects (90.2%) with liver cirrhosis. In total, 30 (73.2%) subjects previously received NS5A inhibitors of the first generation (ledipasvir, daclatasvir, or ombitasvir) and 11 subjects (26.8%) received NS5A inhibitors of the second generation (velpatasvir). All patients received retreatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutation (L31M/V/I and/or Y93H), and the generation of previously used NS5A inhibitors. Observed SVR12 rates were as follows: 97.6% (40/41 patients) overall; 100% in patients without cirrhosis (n = 4) versus 97.3% in those with cirrhosis (n = 37); 100% with single L31M/V/I or Y93H mutation (n = 22) versus 94.4% with double mutations (n = 18); 100% in patients who failed previous treatment with first-generation (n = 30) versus 90.9% in those who failedprevious treatment with second-generation NS5A inhibitors (n = 11). Retreatment with 3D + SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection, including those with liver cirrhosis, who failedprevious treatment withDAA containing NS5A inhibitors. Fibrosis stage and single or simultaneous presence of NS5A RASs L31M/V/I and Y93H at the baseline, as well as the generation of previously used NS5A inhibitors, did not impact SVR12 rates.

Enhancing current human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C virus co-infection management.

Enhancing current human immunodeficiency virus/hepatitis B and human immunodeficiency virus/hepatitis C virus co-infection management.

Use of Direct-Acting Antiviral Agents and Survival Among Medicare Beneficiaries with Dementia and Chronic Hepatitis C.

Many patients with Alzheimer's disease and related dementia (ADRD) have chronic hepatitis C due to the high prevalence of both conditions among elderly populations. Direct-acting antivirals (DAAs) are effective in treating hepatitis C virus (HCV). However, the complexity of ADRD care may affect DAA use and outcomes among patients with HCV and ADRD. Little information exists on uptake of DAAs, factors associated with DAA use, and health benefits of DAAs among patients with HCV and ADRD. To examine use and survival benefits of DAAs in Medicare patients with HCV and ADRD. The study included Medicare patients with HCV between 2014 and 2017. We estimated Cox proportional hazards regressions to examine the association between having ADRD and DAA use, and the relation between DAA use and survival among patients with HCV and ADRD. The adjusted hazard of initiating a DAA was 50% lower in patients with ADRD than those without ADRD (adjusted HR = 0.50, 95% CI: 0.46-0.54). The hazard of DAA use among ADRD patients with behavioral disturbances was 68% lower than non-ADRD patients (adjusted HR = 0.32, 95% CI: 0.28-0.37). DAA treatment was associated with a significant reduction in mortality among ADRD patients (adjusted HR = 0.52, 95% CI: 0.44-0.61). The rate of DAA treatment in patients with HCV and ADRD was low, particularly among those with behavioral disturbance. The survival benefits of DAA treatment for patients with ADRD were substantial.

Direct-acting antiviral agents in lymphoproliferative disorders: more complex than expected.

Direct-acting antiviral agents in lymphoproliferative disorders: more complex than expected.

All-Cause Mortality and Causes of Death in the Swiss Hepatitis C Cohort Study (SCCS).

BackgroundWith direct-acting antiviral agents (DAAs), mortality rates and causes of death among persons with hepatitis C virus (HCV) infection may change over time. However, the emergence of such trends may be delayed by the slow progression of chronic hepatitis C. To date, detailed analyses of cause-specific mortality among HCV-infected persons over time remain limited.MethodsWe evaluated changes in causes of death among Swiss Hepatitis C Cohort Study (SCCS) participants from 2008 to 2016. We analyzed risk factors for all-cause and cause-specific mortality, accounting for changes in treatment, fibrosis stage, and use of injectable drugs over time. Mortality ascertainment was completed by linking lost-to-follow-up participants to the Swiss Federal Statistical Office death registry.ResultsWe included 4700 SCCS participants, of whom 478 died between 2008 and 2016. The proportion of unknown causes of death decreased substantially after linkage, from 42% to 10%. Leading causes of death were liver failure (crude death rate 4.4/1000 person-years), liver cancer (3.4/1000 person-years), and nonliver cancer (2.8/1000 person-years), with an increasing proportion of cancer-related deaths over time. Cause-specific analysis showed that persons with sustained virologic response were less at risk for liver-related mortality than those never treated or treated unsuccessfully.ConclusionsAlthough the expected decrease in mortality is not yet observable, causes of death among HCV-infected persons have evolved over time. With the wider use of DAAs, liver-related mortality is expected to decline in the future. Continued monitoring of cause-specific mortality will remain important to assess the long-term effect of DAAs and design effective interventions.

Eradication of Hepatitis C Virus (HCV) Improves Survival of Hepatocellular Carcinoma Patients with Active HCV Infection - A Real-World Cohort Study.

BackgroundHepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) infection has become less and less due to the use of direct-acting antiviral agents (DAAs). Although it may be common to assume that eradication of the virus should improve the survival of HCC patients, large-scale randomized clinical data to support the correlation between viral load and prognosis are still lacking in China. The aim of the study was to evaluate the efficacy of antiviral therapy for HCC patients with active HCV infection.Patients and MethodsWe retrospectively enrolled 80 HCC patients with active HCV infection. Active HCV infection was defined as positive for HCV antibody with detectable HCV RNA by polymerase chain reaction.ResultsForty-four patients (55.0%) received interferon combined with ribavirin treatment and 23 patients achieved sustained virological response (SVR). The 1-year survival rate in patients who achieved SVR was the highest, followed by those with non-SVR after antiviral treatment, and those without antiviral therapy (1-year survival rate were 91.3%, 88.4%, and 73.1%, respectively, P = 0.012). In the univariate analysis, alcohol intake and alpha-fetoprotein >20 ng/mL were associated with lower overall survival (OS) (P = 0.025 and P = 0.044, respectively), while SVR after antiviral treatment was associated with longer OS (P = 0.016). In the multivariate analysis, only SVR after antiviral treatment was significantly associated with OS (P = 0.014).ConclusionOur results ensured that the elimination of HCV substantially improved OS in HCC patients with active HCV infection, and the prognosis of those patients without antiviral therapy was poor.

Changing indications for liver transplant: slow decline of hepatitis viruses in Italy

Background: The indications to LT are changing rapidly in Europe and the U.S. mainly due to the extensive use of direct-acting antiviral agents (DAA) against HCV. Italy was an endemic area for viral hepatitis.Methods: The study reviewed liver transplant registry of a leading Italian centre from the year 2014 (the year before the extensive use of DAA in Italy) to December 2018, with the scope of recording trends in indications. The indications were categorised as: HCV; HBV ± HDV; alcohol-dependent liver disease (ALD); NASH; mescellaneous. Transplants for decompensation or hepatocellular carcinoma were analysed separately. The data were analysed using standard statistical methods.Results: During the study period 463 LTs were accomplished. For the scope of the present study second transplants and transplant in patients <18 years were eliminated; in all, 397 patients were analysed. Overall, HCV infection was the main aetiological factor leading to transplant (139/397, 35%) followed by alcohol use (20.9%), HBV ± HDV (15.8%) and NASH (12.8%). In the decompensation group HCV decreased from 41.9% in 2014 to 14.3% in 2018 while alcohol increased (p < .001); in the HCC group, HCV decreased from 52.6% to 34% and alcohol and NASH increased; the number and proportion of HBV infections remained stable over time, with a 56% prevalence of HDV among decompensated patients.Conclusion: LT landscape is rapidly evolving; hepatitis virus infections still maintain a remarkable proportion among the indications for LT in an area that reached in the past high endemic levels for hepatitis C and B.

Retreatment of patients with chronic hepatitis C, subtype 1b and cirrhosis, who failed previous direct-acting antiviral therapy including first- and second-generation NS5A inhibitors with ombitasvir/paritaprevir/ritonavir, dasabuvir+sofosbuvir+ribavirin.

The use of direct-acting antiviral agents (DAAs) in patients with chronic HCV genotype 1 infection results in sustained virologic response (SVR) rates of 95%-97%, but 3%-5% of patients experience virologic failure. We observed 17 patients infected with HCV subtype 1b who failed previous treatment with DAA, including 13 subjects (76.5%) with liver cirrhosis. Twelve subjects (70.6%) previously received NS5A inhibitors of the first generation (ledipasvir or daclatasvir) and five subjects (29.4%) - the second generation (velpatasvir). All patients were retreated with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutations (L31M/V/I and/or Y93H), and on the generation of previously used NS5A inhibitor. Observed SVR12 rates were as follows: 94.1% (16/17 patients) overall; 100% in patients without cirrhosis (n=4) vs 92.3% in those with cirrhosis (n=13); 100% with single L31M/V/I or Y93H mutation (n=7) vs 88.9% with double mutations (n=9); 100% in patients who previously failed first generation (n=12) vs 80.0% in those failed second-generation NS5A inhibitors (n=5). Retreatment with 3D+0SOF+RBV was highly effective and safe in patients with chronic HCV GT1b infection who failed previous use of NS5A inhibitors. Fibrosis stage, baseline presence of NS5A RAS mutations and the generation of previously used NS5A inhibitors may impact the probability of achieving SVR12 , but statistical significance was not demonstrated in our small retrospective cohort. Further studies in a larger population are needed to confirm or not the predictive value of these baseline factors.

HCV treatment in 2020: How to translate highly effective therapies into elimination strategies.

The hepatitis C virus (HCV) is among the most common blood-borne infections worldwide and a major cause of cirrhosis and hepatocellular carcinoma. HCV was first identified in 1989. The current use of direct-acting antiviral agents (DAAs) to cure HCV reflects rapid diagnostic and therapeutic advances in a short period of time that is seen in few diseases. Both the cost and access to DAAs have improved since the introduction of these therapies in 2014. While HCV is very easy to treat, it will be difficult to eliminate worldwide. The tools exist to create strategies to treat and eliminate HCV as a public health threat; however, elimination of HCV will involve improving access to diagnostic testing for HCV with confirmation of active infection. Models of care will need to be revised from centralized, specialized care to decentralized, point-of-care treatment for HCV patients. These models should include clinics that care for populations with a high prevalence of HCV, such as those treating intravenous drug users, needle exchange services, community health centers, and prisons, in addition to primary care clinics. These care pathways are feasible because of the simplicity of pan-genotypic therapies for HCV that require minimal monitoring. Many countries and regions of the world have embarked on programs with the goal of achieving the World Health Organization target of elimination by 2030. Best practices in HCV elimination should be shared globally.

The prevalence of HBsAg / HCV in Aksaray province, demographic data of patients with HCV and the rates of access to new treatments

Aim: Approximately 210 million peoples worldwide are estimated to be infected with chronic HCV. Nowadays, with the use of direct-acting antiviral agents, sustained viral response rates of more than 95% have been achieved in HCV. In our country, these drugs have been used for the last two years. The desired results could not be reached in the number of patients reaching treatment. In this study, we investigated the prevalence of HBsAg and HCV in Aksaray. In addition, we aimed to reveal the demographic characteristics of patients infected with HCV, their awareness about the disease and the rates of access to treatment. Material and methods: In this study, 11716 patients admitted to Aksaray Training and Research Hospital Gastroenterology, Infectious Diseases Outpatient Clinic and Endoscopy Unit between January 2016 and October 2018 were retrospectively screened. HCV positive patients were called from their contact numbers. Results: HBsAg was detected in 244 (2.08%) and anti-HCV positivity in 71 (0.6%) of 11716 patients. Fifty-three patients with HCV were included in the study. 16 patients could not be reached. Nine of these patients were treated with new treatment regimens at the external center. Nine patients were reached during this study and were provided access to treatment. All of these patients were able to tolerate treatment and a permanent viral response was found. Conclusion: Direct effective antiviral agents are effective and safe drugs in patients with HCV. Additional efforts and means of communication are needed to enable patients to access drugs.

Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register).

Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting. An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens. Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin. Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.

Trends in Mortality From Extrahepatic Complications in Patients With Chronic Liver Disease, From 2007 Through 2017

Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States. We performed a population-based study using US Census and the National Center for Health Statistics mortality records from 2007 through 2017. We identified trends in age-standardized mortality using Joinpoint trend analysis with estimates of annual percent change. The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study, age-standardized mortality from hepatitis B virus-related extrahepatic complications increased by an average of 2.0% each year. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly. In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.