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.

Clinical Outcomes of Radiological Treatment Modalities of Hepatocellular Carcinoma: A Single-Center Experience from Saudi Arabia.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Most patients with HCC are unsuitable for surgical therapies. Therefore, nonsurgical therapies play a central role in the management of this disease. Several percutaneous treatment modalities are available for HCC including radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). In this study, we aim to evaluate the clinical outcomes, morbidity and mortality rates, and survival rates of four treatment modalities for HCC (RFA, TACE, TARE, and Sorafenib) and compare the success rate of each modality. METHODS: A retrospective observational study was conducted at King Abdulaziz Medical City in Jeddah, Saudi Arabia. The inclusion criteria were composed of patients diagnosed with HCC who received RFA, TACE, TARE, or Sorafenib treatments between 2008 and 2017. The primary outcome of this study was recurrence-free patients at the last follow-up. RESULTS: A total of 108 patients were included in this study. The mean age of the patients was 68.01 ± 9.98 years. Eighty-Two patients (75.9%) underwent interventions with the intention to cure or stabilize HCC, while twentysix patients (24.1%) were started on Sorafenib as a palliative treatment. The five years recurrence-free rates were 41.2% with RFA, 40% with the combination of TACE and RFA, 23.3% with TACE, and 0% with TARE. All patients on Sorafenib died from advanced-stage HCC. CONCLUSION: This study provides further evidence for the efficacy of several treatment modalities for the management of HCC. RFA and the combination of TACE and RFA showed better outcomes with a recurrence-free rate reaching up to 40%. TACE had a moderate survival benefit up to 23.3%. TARE showed negative survival benefits. Sorafenib continues to be an important palliative treatment but does not offer curative potential.

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.

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.

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.

Acute Pancreatitis: A Complication of Intragastric Balloon.

PURPOSE: This study was carried out because intragastric balloon (IGB) is a widely used method to combat obesity, and acute pancreatitis complicating IGB is rare and yet to be understood. METHOD: This study was a retrospective analysis of all patients with a history of IGB insertion, who developed acute pancreatitis before balloon removal. RESULTS: A total of 4 cases were found, with a mean age of 27±2.9 years. The mean duration of IGB insertion was 2.25±1.25 months, with an average body mass index of 37.7±3.4 kg/m. Abdominal computed tomography visualized signs of pancreatitis with the balloon compressing the pancreatic body. Pancreatitis resolved after endoscopic balloon extraction, with an average aspiration of 607.5±64.5 mL of the fluid used to fill the balloon. CONCLUSION: Our study demonstrates that acute pancreatitis can complicate IGB and recommends the need to measure amylase and lipase in patients who have a history of IGB insertion and present with a picture suggestive of pancreatitis.

Laparoendoscopic Rendezvous for Concomitant Cholecystocholedocholithiasis: A Successful Modality Even in the Most Difficult Presentations Including Pregnancy.

Background. Laparoendoscopic rendezvous (LERV) technique is emerging as an attractive treatment option for concomitant cholecystocholedocholithiasis. In this paper, we report our experience in performing the LERV technique in patients with unusual presentations in terms of anatomical difficulty, pregnancy, multiple comorbid diseases, and postlaparotomy. We aim to highlight the effectiveness of the LERV technique in some clinical situations where conventional methods would fail or carry high risks in adequately managing concomitant cholecystocholedocholithiasis. Methods. Four patients diagnosed to have concomitant cholecystocholedocholithiasis with associated difficult presentation or comorbid diseases were treated using the LERV technique. One patient presented with difficult anatomy where ERCP failed at initial attempts. Another patient was pregnant (first trimester). A third patient had complex comorbid diseases (bronchial asthma, hypertension, congestive heart failure, and end-stage renal disease on regular hemodialysis). A fourth patient had previous laparotomy and sigmoidectomy for diverticular disease and had severe hospital phobia. Results. All patients tolerated the LERV technique very well; no intraoperative occurrence was reported. The mean operative time was 86.3 ± 17.2 minutes; mean time of the endoscopic part was 29.4 ± 3.57 minutes. The mean blood loss was 44.3 ± 18.2 mL (range 20-85). Residual stone, postoperative complications, postoperative morbidity, and postoperative mortality were 0 (0%). Postoperative short hospital stay was reported in all patients, average 3 days (range 2-4). Conclusion. LERV procedure is a safe and effective treatment option for the management of concomitant cholecystocholedocholithiasis, even in difficult situations where other methods would fail or carry high risks, or in patients presenting with severe comorbid diseases or pregnancy. This procedure may emerge as an attractive alternative option for high-risk patients. A patient's wishes may also influence the selection of this procedure. More scientific studies recruiting more patients should be done in order to standardize the LERV procedure.

Sustained virological response in a predominantly hepatitis C virus genotype 4 infected population.

AIM: To assess sustained virological response (SVR) rates in a predominantly hepatitis C virus (HCV) genotype 4 infected population. METHODS: Between 2003-2007, 240 patients who were treated for chronic hepatitis C infection at our center were included. Epidemiological data, viral genotypes, and treatment outcomes were evaluated in all treated patients. Patients with chronic renal failure, previous non-responders, and those who relapsed after previous treatment were excluded from the study. Among all patients, 57% were treated with PEG-interferon (IFN) alpha-2a and 43% patients were treated with PEG-IFN alpha-2b; both groups received a standard dose of ribavirin. RESULTS: 89.6% of patients completed the treatment with an overall SVR rate of 58%. The SVR rate was 54% in genotype 1, 44% in genotype 2, 73% in genotype 3, and 59% in genotype 4 patients. There was no statistical difference in the SVR rate between patients treated with PEG-IFN alpha-2a and PEG-IFN alpha-2b (61.5% vs 53%). Patients younger than 40 years had higher SVR rates than older patients (75% vs 51%, P = 0.001). SVR was also statistically significantly higher when the HCV RNA load (pretreatment) was below 800.000 (64% vs 50%, P = 0.023), in patients with a body mass index (BMI) less than 28 (65% vs 49%, P = 0.01), and in patients who completed the treatment duration (64% vs 8%, P

Pediatric-onset primary biliary cirrhosis.

Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has not been reported in childhood. We report 2 cases of PBC diagnosed at 16 and 15 years of age, respectively. The first girl was noted to have increased liver enzyme levels at 16 years of age. Antimitochondrial antibody (AMA) was strongly positive, and serum quantitative immunoglobulin M level was 8.26 g/L (normal, 0.6-3 g/L). A liver biopsy specimen showed stage II PBC. Despite treatment with ursodeoxycholic acid, she developed progressive cholestasis, intractable pruritus, and a significant sensory neuropathy and weight loss eventually requiring liver transplantation. Her mother had PBC/autoimmune overlap syndrome and underwent successful liver transplantation at 34 years of age. The second girl had persistently elevated liver enzyme levels following cholecystectomy at 15 years of age for symptomatic cholelithiasis. Endoscopic retrograde cholangiopancreatography showed no abnormalities. AMA was positive at 1:160, and serum quantitative immunoglobulin was 6.96 g/L. A liver biopsy specimen showed stage II PBC, and her liver enzyme levels almost normalized after starting treatment with ursodeoxycholic acid. In conclusion, we present 2 liver biopsy-confirmed cases of pediatric-onset AMA-positive PBC. With increased awareness of early-onset PBC, further pediatric cases may be discovered.