Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

BACKGROUND: We evaluated the diagnostic accuracy of aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), AST/alanine aminotransferase (ALT) ratio (AAR), and age-platelet index (API) for significant fibrosis (Metavir F2-4) in low-replicative (HBV DNA <20,000 IU/mL) chronic hepatitis B virus (HBV) patients. METHODS: The sensitivity, specificity, and area under the receiver-operating characteristic curve (AUROC) of HBeAg-negative, low-replicative (n = 213) and high-replicative (HBV DNA ≥20,000 IU/mL, n = 153) patients was assessed. RESULTS: Overall, 113 patients (30.9%) had F2-4 fibrosis. Of the low and high-replicative patients, 40 (18.8%) and 73 (47.7%) had F2-4, respectively (P < 0.0001). APRI ≥0.5 less frequently identified F2-4 fibrosis in low vs. high-replicative patients (48.7% vs. 69.6%, P = 0.032) and AAR identified it more frequently in low-replicative patients (37.5% vs. 19.4%, P = 0.037). FIB-4 and API were not different (P > 0.05) for identifying F2-4 fibrosis in low and high-replicative patients. Higher specificities were seen at the lowest cut-offs in low vs. high-replicative states for APRI (≥0.5, 98% vs. 68.9%), AAR (84.3% vs. 76.6%), FIB-4 (≥1.45, 97.5% vs. 87.8%) and API (>4, 94.8% vs. 93.8%). At ROC-defined thresholds, APRI (≥0.33), AAR (≥0.93), FIB-4 (≥0.70) and API (>2) showed greater AUROCs for F2-4 diagnosis in low replicative (0.80, 0.62, 0.81 and 0.71, respectively) vs. high-replicative patients (0.73, 0.52, 0.67 and 0.69, respectively). CONCLUSION: All 4 biomarkers in both, low and high-replicative HBV demonstrate modest accuracy for fibrosis diagnosis at conventional cut-offs. Lowering the cut-offs may increase the diagnostic relevance of these biomarkers, particularly for APRI and FIB-4 in low-replicative disease.

SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024.

ABSTRACT: Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.

Accuracy of international guidelines for identifying significant fibrosis in hepatitis B e antigen--negative patients with chronic hepatitis.

BACKGROUND & AIMS: Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis. METHODS: We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen-negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173). RESULTS: Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P < .0001). In applying the EASL, AASLD, APASL, and USPA criteria, sensitivity and specificity values for detection of ≥F2 fibrosis were 45.6%, 58.5%, 56.3%, and 45.7% (P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% (P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61-0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58-0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59-0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54-0.64; P = .013). CONCLUSIONS: In hepatitis B e antigen-negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.

Efficacy of ursodeoxycholic acid for primary biliary cholangitis: Experience from a tertiary care centre in Saudi Arabia.

Background: Primary biliary cholangitis (PBC) is a progressive autoimmune cholestatic liver disease that primarily affects females more than males and may lead to end-stage liver disease. We studied baseline characteristics, and the biochemical and clinical response to ursodeoxycholic acid (UDCA), a first-line treatment option for patients with PBC, in a cohort of patients diagnosed with PBC from Saudi Arabia. Methods: A total of 30 patients meeting the diagnostic criteria of PBC who were being followed in the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, between January 1, 2008, and December 31, 2017, were enrolled in the study. The patients with autoimmune hepatitis, primary sclerosing cholangitis, and overlap syndromes were excluded. The baseline characteristics of the patients were recorded. The response to UDCA treatment was assessed according to the Barcelona, Paris I, Paris II, and Toronto criteria, and clinical outcomes, and biochemical changes were ascertained. Results: The mean age was 46 years ± 11.7 with a female gender predominance of 93% (n = 28). Pruritus was the predominant symptom reported by 90% (n = 27) of the patients. A total of 23 (77.7%) patients underwent liver biopsy and all of them showed histological features suggestive of PBC. Cirrhosis was documented in 30% (n = 9) of the patients at baseline. Overall, 86.7% (n = 26) of the patients were positive for antimitochondrial antibodies. The biochemical response rates to UDCA based on Paris I, Paris II, Barcelona, and Toronto criteria were 73.3, 40, 56.7, and 53.3%, respectively. Conclusion: Over 10 years, 30 patients with PBC were diagnosed at a large referral center in Saudi Arabia. The response to UDCA treatment was inadequate.

Effectiveness of generic sofosbuvir in the treatment of chronic hepatitis C virus infection in Saudi patients.

OBJECTIVES: To assess the effectiveness of generic sofosbuvir (SOF) and branded daclatasvir (DCV) for the treatment of chronic hepatitis C virus (HCV)infected patients. METHODS: This retrospective study, performed in a single center in Saudi Arabia between August 2017 and July 2022, we enrolled 140 consecutive patients with HCV who received generic SOF and branded DCV. The primary outcome was sustained virologic response at week 12 (SVR12). RESULTS: The majority of the patients were female (62.1%), infected with genotype 4 (57.9%), and treatment-naïve in 120 (85.7%) patients with baseline cirrhosis in 55 (39.3%). The mean patient age was 61±13.6 years. In the intention-to-treat analysis, 131 (93.6%) patients achieved SVR12. Moreover, 85.7%, 100%, 100%, 88.9%, and 96.3% of genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. In the per-protocol analysis, 131 (96.3%) patients achieved an SVR of 12. Additionally, 92.3%, 100%, 100%, 88.9%, and 98.7% of the patients with genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. No HCV virologic breakthroughs occurred. In the subgroup analysis, SVR12 rates were comparable regardless of baseline characteristics, such as treatment history, cirrhosis, and hepatocellular carcinoma. Patients achieving SVR12 showed a significant improvement in post-treatment serum liver enzyme and total bilirubin levels. CONCLUSION: The findings of our study confirm the effectiveness of generic sofosbuvir as a treatment option for HCV infection.

Endoscopic extraction of vascular embolization coils that have migrated into the biliary tract in a liver transplant recipient.

Hepatic artery pseudoaneurysm (HAA) is a rare vascular complication of liver transplantation. Minimally invasive radiological interventions are generally considered before seeking surgical treatment of HAA. Coil embolization of the aneurysmal sac and or exclusion of pseudoaneurysm by deploying a stent over the aneurysm are effective interventions to control hemobilia arising from the HAA. Migration of coils inside the bile duct is a rarely reported complication in post-hepatic transplantation. Treatment options remain largely unexplored due to the rarity of its occurrence. Endoscopic retrograde cholangiographic removal of migrated vascular coils in the common bile duct following embolization of HAA has not been described in a liver transplant setting. We report a liver transplant recipient who underwent uneventful and successful endoscopic removal of migrated coils into the bile duct.

Lower prevalence of hepatic fibrosis in low viremic hepatitis B patients with fluctuating HBV DNA levels.

Background: In chronic hepatitis B virus (HBV) patients, fluctuations in HBV DNA serve as a "gray area" and impede the accurate identification of inactive carriers. We aimed to assess if such fluctuations impact the presence of significant hepatic fibrosis (Metavir F2-4) in chronic HBV patients. Methods: Consecutive, untreated HBeAg-negative carriers (n = 234) with fluctuating HBV DNA (n = 73) above or below a level of 2000 IU/mL were included and compared to those without fluctuations (n = 161). Patients without fluctuating HBV DNA were further analyzed based on those with persistently low (<2,000 IU/mL, n = 137) and higher HBV DNA (2,000-20,000 IU/mL, n = 24). Hepatic fibrosis (assessed by transient elastography) was correlated with virologic and biochemical profiles. Results: The mean age of the overall cohort was 47.8 ± 11.1 years, of whom 107 (45.7%) were male. During a median of 60 months (interquartile range [IQR] 34-82) of follow-up, 73 (31.2%) patients had a mean of 1.6 ± 0.9 fluctuations in HBV DNA. The median time to the first fluctuation was at 14.5 (IQR 5.0-33.7) months. Patients with fluctuating viremia had higher log10 qHBsAg (3.1 ± 0.8 vs. 2.7 ± 1.0, P = 0.022) and HBV DNA (3.4 ± 0.5 vs. 2.7 ± 0.8, P < 0.001) compared to those without fluctuations. Patients with fluctuant viremia were less likely to have F2-4 fibrosis (8.2%) compared to those without fluctuant viremia (18.2%, odds ratio [OR]: 0.407, 95% confidence interval [CI]: 0.161-1.030; P = 0.052). Males tended to have less fluctuation constituting 37.0% of patients with fluctuating HBV DNA (P = 0.071). Fluctuations occurred more frequently in those with predominantly higher HBV DNA levels (26.0%) compared to those without fluctuations (14.9%; P = 0.030). Conclusions: Fluctuating HBV DNA levels occur frequently but are not associated with significant fibrosis. Minor fluctuations in HBV DNA levels are unlikely to be of clinical relevance.

Saudi association for the study of liver diseases and transplantation position statement on the hepatology workforce in Saudi Arabia.

The field of hepatology has evolved significantly over the last two decades. Hepatology practice in Saudi Arabia (SA) was dominated by hepatitis B and C viruses but is now being overtaken by patients with non-alcoholic fatty liver disease. These patients require greater medical attention as their care is more complex compared to patients with viral hepatitis. In addition, liver transplantation (LT) has expanded significantly in SA over the last three decades. There is a necessity to increase the hepatology workforce to meet the demand in SA. The time has come to reinforce the transplant hepatology fellowship program, that was launched recently, and to develop a nurse practitioner practice model to meet these demands. In addition, SA is going through a health care reform to enhance health care delivery which may affect the financial compensation polices of various specialties including gastroenterology and hepatology. Therefore, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) established a task force to discuss the current and future demands in the hepatology workforce in SA, as well as to discuss different avenues of financial compensation for transplant hepatologists in LT centers.

Effect of erythromycin before endoscopy in patients presenting with variceal bleeding: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Blood in the stomach and esophagus in patients with variceal bleeding often obscures the endoscopic view and makes endoscopic intervention difficult to perform. Erythromycin, a motilin agonist, induces gastric emptying. OBJECTIVE: To assess the effect of erythromycin on endoscopic visibility and its outcome in patients with variceal bleeding. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Tertiary care hospital. PATIENTS: Adult patients with liver cirrhosis presenting with hematemesis within the previous 12 hours. INTERVENTION: Either 125 mg erythromycin or placebo administered intravenously 30 minutes before endoscopy. MAIN OUTCOME MEASUREMENTS: Endoscopic visibility during index endoscopy and mean duration of procedure. SECONDARY OUTCOME MEASUREMENTS: Need for repeat endoscopy and blood transfusions within 24 hours, endoscopy-related complications, and length of hospital stay. RESULTS: A total of 102 patients received either erythromycin or placebo (53 erythromycin and 49 placebo). Forty-seven patients in the erythromycin group and 43 in the placebo group had variceal bleeding and were considered for final analysis. A completely empty stomach was seen in 48.9% of the erythromycin group versus 23.3% of the placebo group (P<.01). Mean endoscopy duration was significantly shorter in the erythromycin group than in the placebo group (19.0 minutes vs 26.0 minutes, respectively; P<.005). Length of hospital stay was significantly shorter in the erythromycin group than in the placebo group (3.4 days vs 5.1 days, respectively; P<.002). The need for repeat endoscopy and the mean number of units of blood transfused did not differ significantly in the 2 groups. No adverse events were observed with erythromycin. LIMITATIONS: Sample size not sufficient to measure the need for repeat endoscopy and survival benefit. CONCLUSIONS: Erythromycin infusion before endoscopy in patients with variceal bleeding significantly improves endoscopic visibility and shortens the duration of the index endoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01060267.).

A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt.

BACKGROUND: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. AIM: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. METHODOLOGY: Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. RESULTS: We estimated that 49.3-64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. CONCLUSION: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection.

Clinical and Metabolic Characteristics of Non-Alcoholic Fatty Liver Disease Patients in Saudi Arabia: Data from the Systematic Observatory Liver Disease (SOLID) Registry.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in Saudi Arabia (SA), but descriptions of the clinical and metabolic characteristics of these patients are limited. The present study aims to fill this gap. METHODS: Demographic, clinical, and laboratory data of all NAFLD patients from 2009 to 2019 were retrieved from the Systematic Observatory Liver Disease Registry (SOLID) [n=832 (337 males; 495 females); mean (± standard deviation, SD) age was 42.6±13.6 years; mean body mass index (BMI) was 35.0±9.3kg/m2]. Non-invasive surrogate scores of fibrosis (eg AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4), and NAFLD fibrosis (NFS) scores) were calculated and analyzed. In addition, data from NAFLD patients with normal and high alanine aminotransferase (ALT) were compared using two different methods: the standard laboratory reference range which defines normal as ALT<61 IU/L, and the range proposed by a recent national study which sets upper limits of normal ALT at 33 IU/l for men and 22 IU/l for women. RESULTS: Hyperlipidemia was the most common comorbidity (41.7%), followed by type 2 diabetes mellitus (T2DM) (35.3%) and hypertension (28.4%). Prevalence of advanced fibrosis varied widely across definitions [FIB-4, N=19 (2.5%); APRI, N=21 (2.8%); NFS, N=62 (8.6%)] and exhibited sexual dimorphism with males having worse metabolic characteristics. NAFLD patients with normal ALT were more likely to be older, female, have a lower BMI, and have a higher prevalence of cirrhosis, DM, hypertension, hyperlipidemia, and renal dysfunction. CONCLUSION: Patients with NAFLD have metabolic characteristics associated with several comorbidities, including NAFLD patients with normal ALT. Mechanistic studies are needed to examine and analyze complex, interactive effects between sex, age, and other factors that may accelerate NAFLD disease progression.

Knowledge and attitude toward organ donation among medical staff and outpatients at King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Organ transplantation is still the treatment of choice for end-stage organ failure. Despite the establishment of the Saudi Center for Organ Transplantation (SCOT), the organ supply still does not meet the increasing demand. This study aims to assess the knowledge of Saudis about organ donation both among the public and the medical staff and to assess the trend in the change from 1996 until now. A cross-sectional study was conducted among Saudis above the age of 18 years. A self-administered, 25-item, questionnaire was completed by participants including both outpatients and medical staff at King Abdulaziz Medical City using a convenient sampling technique. A total of 376 individuals answered the questionnaire; 238 (63.1%) heard about SCOT, of whom 124 (70.5%) were males. Health-care professionals had better attitude and knowledge on organ donation (P <0.05). Compared to the results from 1996to 2017, there was (51.22%) to (30.4%) decrease in people who allowed their families to donate their organs; on the other hand, there was an increase in the percentage of people who had the correct knowledge that Islam supports organ donation. Unsatisfactory levels of awareness impacted negatively on the knowledge and attitude of the population that is showed by the minor improvements over the years, and the slight proportion of participants who owned a donor card. Although 97.6% of the participants knew about the concept of organ donation, only 66.5% were familiar with the positive Islamic opinion. Based on the results of the comparison with the study in 1996, we conclude that more efforts from both the governmental and religious authorities are needed to increase awareness.

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia.

BACKGROUND/AIMS: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. PATIENTS AND METHODS: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). RESULTS: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012). CONCLUSIONS: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.

Can hepatitis C virus be eliminated by 2030? Saudi Arabia as an example.

[No abstract available].

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 ±â€¯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.

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.

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.

Presentation, diagnosis and outcome of predominantly hepatic Wilson's disease in adult Saudi patients: a single centre experience.

BACKGROUND/AIM: To evaluate the clinical manifestations, diagnostic features, disease course and response to treatment among Saudi adults with predominantly hepatic Wilson's disease. A retrospective cohort study of 40 adult patients diagnosed with predominantly hepatic Wilson's disease between 1994 and 2008 at King Abdulaziz Medical City, Riyadh was carried out. PATIENTS AND METHODS: The diagnosis was based on varying combinations of clinical and laboratory evidence of liver disease, presence of Kayser Fleisher rings, low serum ceruloplasmin levels, elevated 24 hour urinary copper excretion and histopathological findings on liver biopsy. RESULTS: The most frequent clinical presentation was decompensated chronic liver disease in 19 (47.5%), followed by chronic hepatitis in 15 (37.5%) and fulminant hepatic failure (FHF) in 5 (12.5%) patients. Eight (20%) patients with end-stage liver disease had liver transplantation, while 24 (60%) patients followed up on medical treatment for a variable period of 1-12 years showed clinical and laboratory improvement. One patient was lost early in follow up. Eight (20%) patients died during the study period, 5 with FHF, and 2 with advanced hepatic and neurological disease and one seven years after liver transplantation. Mortality rate was 100% in FHF without liver transplantation. CONCLUSION: A predominantly hepatic Wilson's disease has varied clinical presentations with decompensated chronic liver disease being the most common among adult patients. Majority of the patients show stabilization of the disease on medical treatment. FHF in Wilson's disease has a grave prognosis without liver transplantation, the later remains a definitive treatment option for decompensated cirrhotics and patients with FHF.