Abdullah S. Alghamdi

Efficacy and Safety of Simeprevir or Daclatasvir in Combination With Sofosbuvir for the Treatment of Hepatitis C Genotype 4 Infection

Introduction: The combination of sofosbuvir (SOF) with simeprevir (SMV) or daclatasvir (DCV) is very effective in treating hepatitis C virus (HCV) infection, particularly genotype (GT) 1. However, the data on GT4 are very limited. We aimed to determine the efficacy and safety of SOF in combination with either SMV or DCV in GT4-infected patients. Patients and Methods: In this real life, prospective, observational study, HCV (GT4) patients (n=96) were evaluated in 2 groups on the basis of the 12-week treatment regimen they received. Group 1 (n=56) patients were treated with SOF and SMV±ribavirin (RBV), whereas group 2 patients were treated with SOF and DCV±RBV (n=40). The primary efficacy endpoint was sustained virologic response 12, whereas the primary safety endpoint was drug discontinuation or occurrence of grade 3/4 adverse events. Results: The mean age was 49±14.6 years (59.4% men). Cirrhosis was present in 53.6% and 35.0% of groups 1 and 2, respectively, whereas 27 patients (48.2%) in group 1 and 21 patients (52.5%) in group 2 had failed prior interferon-based treatment. The median pretreatment HCV-RNA log10 was 6.1 (3.6 to 7.0) and 6.0 (3.6 to 7.2) IU/mL in groups 1 and 2, respectively. RBV was given to 17 patients (30.4%) in group 1 and 2 patients (5%) in group 2. All patients achieved sustained virologic response 12 (100%). Adverse events occurred in 32% of patients (grade 1 and 2), but none discontinued treatment. One patient died in the SMV group (not related to treatment). Conclusions: SMV/SOF or DCV/SOF combinations are safe and highly effective in HCV-GT4 treatment. Cirrhosis and failure of prior interferon-based treatment did not influence treatment response.

Fibroscan: a noninvasive test of liver fibrosis assessment.

Determination of the extent of progress of hepatic fibrosis is important in clinical practice, where it may reflect the severity of liver disease and predict response to treatment. Percutaneous liver biopsy is the gold standard for grading and staging of liver disease. However, liver biopsy is an invasive procedure with certain unavoidable risks and complications. Several methods have been studied in an attempt to reach a diagnosis of cirrhosis by noninvasive means. Fibroscan has been designed to quantify liver fibrosis by means of elastography and found to have reasonably good sensitivity and specificity patterns, especially in patients with advanced fibrosis and can be used as an alternative to liver biopsy.

SASLT guidelines: Update in treatment of Hepatitis C virus infection.

Hepatitis C virus (HCV) has been reported to be on the decline over the past decade, although it remains a major public health concern in Saudi Arabia. Its prevalence in Saudi Arabia is generally uncertain because most studies were conducted more than 10 years ago. However, data from blood donor screening centers indicates prevalence rates of 0.4–1.1%.[1] The premarital screening data in a predominantly young population from a survey among 74662 individuals conducted in the period between January and May 2008, the results of which were published by the Ministry of Health, showed an HCV prevalence of only 0.33%.[2] Similarly, a community-based study in 16–18 years old Saudi adolescents in 2008 showed a prevalence of HCV at 0.22% in the group.[1] The most prevalent genotype is genotype (GT) 4, followed by GT1. HCV GT4 accounts for 60% of the cases, GT1 for 25.9%, GT2 for 4.3%, GT3 for 2.9%, and GT5/GT6 for 0.3%. 6.3% of the cases were of mixed genotypes, predominantly between GT1 and GT4.[3] The most common subtypes of GT4 are 4a (48%) and 4d (39%), followed by subtypes 4n (6%) and others (6%).[4] Up to 63% of Saudi patients have minimal to moderate (Metavir, F0–2) histological disease.[5]

Epidemiology, disease burden, and treatment strategies of chronic hepatitis C virus infections in Saudi Arabia in the new treatment paradigm shift

Background/Aims: Around 101,000 individuals are estimated to be viremic for chronic hepatitis C virus (HCV) in the Kingdom of Saudi Arabia (KSA) in 2014; however, only about 20% have been diagnosed. We aim to assess baseline epidemiology, disease burden, and evaluate strategies to eliminate HCV in KSA. Materials and Methods: The infected population and disease progression were modeled using age- and gender-defined cohorts to track HCV incidence, prevalence, hepatic complications, and mortality. Baseline assumptions and transition probabilities were extracted from the literature. The impacts of two scenarios on HCV-related disease burden were considered through increases in treatment efficacy alone or treatment and diagnosis. Results: In 2030, it is estimated by the base scenario that viremic prevalence will increase to 103,000 cases, hepatocellular carcinoma (HCC) to 470, decompensated and compensated cirrhosis cases to 1,300 and 15,400, respectively, and liver-related mortality to 670 deaths. Using high efficacy treatment alone resulted in 2030 projection of 80,700 viremic cases, 350 HCC cases, 480 liver-related deaths, and 850 and 11,500 decompensated and compensated cirrhosis cases, respectively. With an aggressive treatment strategy, in 2030 there will be about 1,700 viremic cases, 1 HCC case, about 20 liver-related deaths, and 5 and 130 cases of decompensated and compensated cirrhosis, respectively. Delaying this strategy by one year would result in 360 additional deaths by 2030. Conclusions: HCV in KSA remains constant, and cases of advanced liver disease and mortality continue to rise. Considered increases in treatment efficacy and number treated would have a significantly greater impact than increased treatment efficacy alone. The projected impact will facilitate disease forecasting, resource planning, and strategies for HCV management. Increased screening and diagnosis would likely be required as part of a national strategy.

Legionella confirmation in cooling tower water. Comparison of culture, real-time PCR and next generation sequencing

Objectives: To investigate the presence of Legionella spp in cooling tower water. Legionella proliferation in cooling tower water has serious public health implications as it can be transmitted to humans via aerosols and cause Legionnaires’ disease. Methods: Samples of cooling tower water were collected from King Fahd Hospital of the University (KFHU) (Imam Abdulrahman Bin Faisal University, 2015/2016). The water samples were analyzed by a standard Legionella culture method, real-time polymerase chain reaction (RT-PCR), and 16S rRNA next-generation sequencing. In addition, the bacterial community composition was evaluated. Results: All samples were negative by conventional Legionella culture. In contrast, all water samples yielded positive results by real-time PCR (105 to 106 GU/L). The results of 16S rRNA next generation sequencing showed high similarity and reproducibility among the water samples. The majority of sequences were Alpha-, Beta-, and Gamma-proteobacteria, and Legionella was the predominant genus. The hydrogen-oxidizing gram-negative bacterium Hydrogenophaga was present at high abundance, indicating high metabolic activity. Sphingopyxis, which is known for its resistance to antimicrobials and as a pioneer in biofilm formation, was also detected. Conclusion: Our findings indicate that monitoring of Legionella in cooling tower water would be enhanced by use of both conventional culturing and molecular methods.

SASLT practice guidelines: Management of hepatitis C virus infection

This guideline has been approved by the Saudi Association for the Study of Liver diseases and Transplantation and represents the position of the Association. These practice guidelines have been written to assist physicians and other health care providers to aid in the recognition, diagnosis, and management of chronically infected hepatitis C virus (HCV) patients. They are based on a formal review and analysis of published literature on the topic that impact the management of chronic HCV infection, and the experience of the authors in hepatitis C. In addition, various international practice guidelines and consensus documents on management of chronic hepatitis C were considered in the development of these guidelines. The recommendations contained herein suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care related to the disease. Our understanding of the natural history of HCV infection and the potential for therapy of the resultant disease is continuously improving. However, despite the increasing knowledge, areas of uncertainty still exist and therefore clinicians, patients, and public health authorities must continue to make choices on the basis of the evolving evidence. Therefore, these guidelines are intended to be flexible and may be updated periodically as new information becomes available.

High Efficacy of ombitasvir/paritaprevir/ritonavir plus dasabuvir in hepatitis C genotypes 4 and 1–infected patients with severe chronic kidney disease

Limited data have shown high efficacy of co‐formulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in the treatment of hepatitis C virus (HCV) genotype (GT)‐4, and combined with dasabuvir (DSV) in GT1 patients, with chronic kidney disease (CKD) stages 4‐5 (<30 mL/min/1.73 m2). We assessed real‐world safety and efficacy of OBV/PTV/r ± DSV in GT1‐ and 4‐infected patients.

Real Life Efficacy of Ledipasvir/Sofosbuvir in Hepatitis C Genotype 4–infected Patients with Advanced Liver Fibrosis and Decompensated Cirrhosis,,✯✯✯

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. PATIENTS & METHODS This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). RESULTS The mean age of the overall cohort was 59.6 ± 12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). CONCLUSION LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.

Prevalence and molecular characterization of hepatitis D virus in Saudi Arabia: A single-center study

Background/Aims: Hepatitis D virus (HDV) is a defective RNA virus that is dependent on hepatitis B surface antigen (HBsAg) for transmission and replication. HDV significance arises from the possibility of poor prognosis of hepatitis B virus (HBV) infection. In Saudi Arabia, HDV prevalence varied from 8 to 32% before the HBV vaccination program and ranged from 0 to 14.7% after the vaccination program was started. The last study, performed in 2004, showed a prevalence of 8.6% in hospital-based HBV cases and 3.3% in healthy donors. The aim of this study was to investigate the prevalence and molecular characterization of HDV in chronic hepatitis B (CHB) patients at the King Abdulaziz University Hospital in Jeddah, Saudi Arabia by molecular and serological techniques. To the best of our knowledge, this is the first study to detect HDV at the molecular level in Saudi Arabia. Patients and Methods: The study included samples from 182 CHB patients from Jeddah; 13 samples with HBsAg negative were excluded. Samples were tested for HDV-Ab, viral RNA by reverse transcriptase–polymerase chain reaction (RT-PCR) in the HDV L-Ag region and sequence analysis. Results: The mean age of the participants was 44.36 years; 75.1% of the participants were Saudi nationals, 58% were males. Nine samples were positive for HDV-Ab and four were borderline; all were subjected to RT-PCR amplification. Three of the positive HDV-Ab cases and 1 borderline case were positive by RT-PCR. All the positive cases had HBV genotype D, and the positive RT-PCR cases were positive for HBV DNA. One of the HDV viremic samples was of genotype 1 by sequencing. The prevalence of HDV in the study was 7.7%, which was lower in Saudis (6.3%) than in non-Saudis (11.9%). Conclusion: HDV coinfection does not seem to have an effect on the clinical status of the recruited CHB cases in this study. More studies are needed to investigate the genetic diversity in other areas such as the southern parts of the Kingdom.

Pharmacokinetics-Based Adjusted Versus Standard Dose of Ribavirin Does Not Improve Virologic Response Rates in Chronic Hepatitis C Genotype 4 Patients: A Randomized Controlled Trial

Optimal doses of Ribavirin (RBV) for hepatitis C virus (HCV) treatment are not known. To assess the safety and efficacy of PegIFNalfa-2a in combination with an adjusted (ADJ) RBV dose based on early pharmacokinetics versus a fixed standard (STD) dose of RBV in chronic HCV genotype (GT) 4-naive patients in a randomized trial. One hundred eighty-one patients were randomized. The baseline variables were similar in both arms and females were 50.3% of the patients, 76.5% had minimal-moderate fibrosis (F0-2). Sustained virologic response (SVR) was achieved in 99 (54.7%) subjects. SVR was seen in 50/90 (55.6%) of ADJ dose of RBV and 49/91 (53.9%) of STD dose subjects. Prematurely withdrawal or discontinuation of treatment prematurely in the ADJ RBV arm occurred in 11/90 patients (12.2%) compared with 6/91 subjects (6.6%) in the STD arm (P = 0.214). Similarly, virologic relapse was seen in 14/90 (15.6%) patients of the ADJ arm and 12/91 (13.2%) of the STD arm. Anemia grade 3-4 was seen in 36.7% in ADJ versus 17.6% in STD arm (P = 0.003). Occurrence of rapid virologic response and absences of F4 fibrosis predicted SVR in a univariate analysis. However, age, gender, weight, presence of diabetes, baseline alanine aminotransferase, and vitamin D levels were not significantly different in patients achieving SVR. ADJ higher doses of RBV based on its early pharmacokinetics-based RBV do not improve SVR rates in HCV GT4 treated in combination with peg-IFN alpha-2-a versus STD therapy. Patients on ADJ higher doses of RBV experienced higher rates of anemia and require more erythropoietin without increasing SVR.