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.

Predictors of sustained virological response to a 48-week course of pegylated interferon alfa-2a and ribavirin in patients infected with hepatitis C virus genotype 4.

BACKGROUND AND OBJECTIVES: Knowledge of the predictors of sustained viral response (SVR) to pegylated interferon (PEG-INF) alfa-2a and ribavirin (RBV) therapy in patients with hepatitis C genotype-4 (HCV-4) is crucial for selecting patients who would benefit most from therapy. We assessed the predictors of SVR to this combination therapy in Saudi patients with chronic HCV-4 infection. PATIENTS AND METHODS: This retrospective study included 148 patients with HCV-4 infection who underwent clinical, biochemical and virological assessments before treatment and at 12, 24, 48 and 72 weeks post-treatment. RESULTS: Of the 148 patients, 90 (60.8%) were males. Mean (SD) for age was 48.5 (12.7) years and BMI was 27.9 (7.5) kg/m(2). Seventy-nine of 148 (60.1%) patients were treatment naïve and 110 (74.3%) underwent pre-treatment liver biopsy. Eighteen (12.2%) patients did not complete therapy because of side effects or they were lost to follow up. Early virological response was achieved in 84 of 91 (92.3%) patients. In the 130 (87.8%) patients who completed therapy, 34 (26.2%) were non-responders and 96 (63.8%) achieved end-of-treatment virological response (ETVR). SVR and virological relapse (24 weeks after ETVR) occurred in 66/130 (50.7%) and 30/130 (31.2%) patients, respectively. Compared to relapsers, sustained responders were significantly younger (P=.005), non-diabetic (P=.005), had higher serum albumin (P=.028), lower alpha-fetoprotein level (P=.026), lower aspartate aminotransferase (AST) (P=.04) levels, and were treatment-naïve (P=.008). In a multivariate regression analysis, the independent predictors of SVR were younger age (P=.016), lower serum AST (P=.012), and being treatment naïve (P=.021). CONCLUSION: Approximately half of HCV-4 patients who complete the course of combination therapy achieve an SVR, especially if they are young, treatment naA ve and have lower AST levels.

Sustained virologic response to peginterferon alpha-2a and ribavirin in 335 patients with chronic hepatitis C: a tertiary care center experience.

BACKGROUND/AIM: This retrospective study assessed the efficacy, safety, and the predictors of sustained viral response (SVR) to a 48-week-course of peginterferon alpha-2a (Pegasys) and ribavirin combination therapy in 335 consecutive Saudi patients with chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS: Clinical, biochemical, and virological parameters were collected at time 0 (pretreatment) and at 12, 24, 48, and 72 weeks posttreatment. The mean +/- SD age was 49.1 +/- 13.0 years; 229 (68.4%) were males, mean +/- SD body mass index was 27.8 +/- 7.4, 85 (25.4%) were diabetic, 25 (7.5%) had renal impairment, 136 (40.6%) had previously received interferon +/- ribavirin therapy, and 247 (73.7%) underwent pretreatment liver biopsy. Patients with genotypes 1, 2 or 3, 4 and mixed genotype were 60 (22.15%), 30 (11.0%), 148 (54.4%), and 34 (12.5%), respectively. RESULTS: Early viral response (>or=2-log10 HCV-RNA decline 12 weeks posttreatment) was achieved in 253 (75.3%). Patients who completed 48 weeks of treatment were 292 (87.1%); of these, 121 (75.6%) achieved ETVR, 161 (55.1%) continued to have SVR and 60 (20.5%) had a viral relapse following end-of-treatment response, that is 48.1 and 17.9% of all patients (n = 335), respectively. Nonresponders (NR) were 71 (24.3%) patients and 43 (12.8%) were unable to complete treatment (due to side effects or loss to follow up). Compared to the relapsers, patients with SVR were significantly younger (P = 0.000), nondiabetics (P = 0.015), had higher serum albumin (P = 0.007), had less pretreatment inflammatory grade (P = 0.011), infected with genotypes 2 or 3 (P = 0.014), and treatment-naïve patients (P = 0.001). However, in stepwise multivariate logistic regression analysis, only treatment naiveté and low pretreatment inflammatory score were the independent predictors of SVR (P = 0.005 and P = 0.018, respectively). CONCLUSION: Combination therapy, if tolerated and completed, is effective in treating chronic HCV patients, especially those with no previous interferon therapy and lower pretreatment inflammatory grade.

Six Minute Walk Test to assess functional capacity in chronic liver disease patients.

AIM: To examine the utility of Six Minute Walk Test (6MWT) in patients with chronic liver disease (CLD). METHODS: Two hundred and fifty subjects between the ages of 18 and 80 (mean 47) years performed 6MWT and the Six Minute Walk Distance (6MWD) was measured. RESULTS: The subjects were categorized into four groups. Group A (n = 45) healthy subjects (control); group B (n = 49) chronic hepatitis B patients; group C (n = 54) chronic hepatitis C patients; group D (n = 98) liver cirrhosis patients. The four groups differed in terms of 6MWDs (P < 0.001). The longest distance walked was 421 +/- 47 m by group A, then group B (390 +/- 53 m), group C (357 +/- 72 m) and group D (306 +/- 111 m). The 6MWD correlated with age (r = -0.482, P < 0.01), hemoglobin (r = 0.373, P < 0.001) and albumin (r = 0.311, P < 0.001) levels. The Child-Pugh classification was negatively correlated with the 6MWD in cirrhosis (group D) patients (r = -0.328, P < 0.01). At the end of a 12 mo follow-up period, 15 of the 98 cirrhosis patients had died from disease complications. The 6MWD for the surviving cirrhotic patients was longer than for non-survivors (317 +/- 101 vs 245 +/- 145 m, P = 0.021; 95% CI 11-132). The 6MWD was found to be an independent predictor of survival (P = 0.024). CONCLUSION: 6MWT is a useful tool for assessing physical function in CLD patients. We suggest that 6MWD may serve as a prognostic indicator in patients with liver cirrhosis.

Validation of three noninvasive laboratory variables to predict significant fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia.

BACKGROUND: We tested the clinical utility of the platelet count, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the AST to platelet ratio index (APRI) score in predicting the presence or absence of advanced fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia. METHODS: Liver biopsy procedures performed on chronic hepatitis C patients in our gastroenterology unit at King Khalid University Hospital were traced from records between the years 1998 to 2003. The hospital computer database was then accessed and detailed laboratory parameters obtained. By plotting receiver operating characteristic curves (ROC), three selected models (platelet count, AST/ALT ratio, and the APRI score was the one associated with the highest area under the curve (AUC)=0.812 (95% CI, 0.756-0.868) on the ROC curves, compared to the platelet count and AST/ALT ratio, which yielded an AUC of 0.783 (0.711-0.855) and 0.716 (0.642-0.789), respectively. CONCLUSION: The APRI score seemed to be the best predictive variable for the presence or absence of advanced fibrosis in Saudi hepatitis C patients.

Hepatitis B genotypes: relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia.

AIM: To identify the most common hepatitis B virus (HBV) genotype in Saudi Arabia, and correlate the prevailing genotypes with the clinical outcome of patients. METHODS: Patients were consecutively recruited from the hepatology clinics of two tertiary care referral centers. Patients were categorized into 4 different groups: group 1, patients with hepatitis B and normal liver enzymes; group 2, patients with hepatitis B and abnormal liver enzymes but without cirrhosis; group 3, patients with hepatitis B and liver cirrhosis; group 4, patients with hepatitis B and hepatocellular carcinoma. All patients had a positive hepatitis B surface antigen (HBsAg). Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence and hybridization with sequence-specific oligonucleotides. RESULTS: Seventy patients were enrolled in this study. They were predominantly male (72.9%) in their mid-forty's (mean age 47 years). Forty-nine (70%) patients were hepatitis B envelope antigen (HBeAg) negative. The majority of patients (64%) acquired HBV through unknown risk factors. Hepatitis B genotyping revealed that 57 patients (81.4%) were genotype D, 1 patient (1.4%) had genotype A, 1 patient (1.4%) had genotype C, and 4 patients (5.7%) had genotype E, while 7 patients (10%) had mixed genotype (4 patients ADG, 1 patient DE, 1 patient DF, and 1 patient ADFG). Based on univariate analysis of genotype D patients, significant predictors of advanced liver disease were age, gender, aspartate transaminase, alanine transaminase, albumin, bilirubin, and alkaline phosphatase (all P < 0.001). In multivariate analysis decreased hemoglobin (r = -0.05; 95% CI: -0.08 to -0.03; P = 0.001) and albumin levels (r = -0.004; 95% CI: -0.007 to -0.001; P = 0.002) were highly significant predictors of advanced liver disease. In patients with HBV genotype D, HBeAg negativity was found to increase across advancing stages of liver disease (P = 0.024). CONCLUSION: This study highlights that the vast majority of Saudi patients with chronic hepatitis B have genotype D. No correlation could be observed between the different genotypes and epidemiological or clinical factors. The relationship between genotype D and HBeAg status in terms of disease severity needs to be further elucidated in larger longitudinal studies.

Histological and laboratory features of patients undergoing liver biopsy at a university hospital in Central Saudi Arabia.

OBJECTIVE: To identify the most common liver pathologies seen in our center, to find the prevalence of advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C, and to correlate the histological and laboratory features of the most common diseases and compare between them. METHODS: Liver biopsy procedures performed in our Gastroenterology Unit at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia were traced from records between the years 1997-2003. Clinical, histopathological, and laboratory features were recorded. RESULTS: We identified 574 liver biopsies during the study period. Of the 502 included patients, males were 58.6%. The mean age of the patients was 43.5 years. Approximately half of the biopsies (49%) were performed for patients with hepatitis C, followed by hepatitis B, for which 17% of the biopsies were performed. Patients with hepatitis B were approximately 10 years younger than patients with hepatitis C (p = 0.01). They were 10% more likely to be males. In terms of fibrosis, only approximately 17% of patients with hepatitis B and 27% of patients with hepatitis C had advanced fibrosis. CONCLUSION: Most liver biopsies performed in our center are performed for patients with hepatitis C. Rates of advanced fibrosis in our series are significantly lower than what was previously reported in other studies.