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.

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.

Quantitative HBsAg levels do not identify hepatic fibrosis in HBeAg-negative chronic hepatitis B patients.

BACKGROUND/AIMS: Quantitative serum hepatitis B surface antigen (qHBsAg) has been evaluated in limited patient groups as a marker of histological fibrosis. The accurate identification of inactive chronic hepatitis B virus (HBV) carriers from those with active carriers is difficult because of wide and frequent HBV DNA fluctuations. We aimed to assess the utility of qHBsAg in distinguishing histologically significant fibrosis in untreated HBeAg-negative chronic HBV patients. PATIENTS AND METHODS: qHBsAg levels were measured at baseline as single-point quantification and correlated with virologic and biochemical profiles of consecutive carriers (median, 29; range, 12-110 months). HBeAg-negative patients (n = 75) with HBV DNA <2000 (n = 5), 2000-20,000 (n = 16) and >20,000 IU/mL (n = 54) were included and all had liver biopsy. A qHBsAg cutoff point of 1000 IU/mL was assessed to demonstrate whether it better delineated patients with non-significant histology (F0-1, inflammatory grade A0-1). RESULTS: Mean age of the patients was 39.4 ± 11.4 years and 58 (77.3%) were male. Patients with qHBsAg levels >1000 IU/mL were more likely to be males (84.5%, P = 0.006) or with elevated AST (68.4%, P = 0.0002) and ALT levels (72.4%, P < 0.0001), higher HBV DNA (log10 6.4 ± 1.4, P < 0.0001) and those with F2-4 fibrosis (48.3%, P = 0.028). Serum log10 qHBsAg were significantly lower in patients with HBV DNA <2000 (2.80 ± 1.47) and HBV DNA 2000-20,000 (2.71 ± 0.83) vs. >20,000 IU/mL (3.89 ± 0.61, P < 0.0001). Overall, qHBsAg were not different in patients with F0-1 (3.44 ± 0.91) and F2-4 fibrosis (3.74 ± 0.85, P = 0.161). Serum qHBsAg were higher in patients with significant (A2-3) inflammation (3.85 ± 0.72) compared to A0-1 (3.38 ± 0.95; P = 0.018). Serum qHBsAg demonstrated poor accuracy (AUROC, 0.61, P = 0.111) in identification of F2-4 fibrosis. CONCLUSION: Serum qHBsAg levels do not help differentiate between those with HBV DNA <2000 or 2000 - 20,000 IU/mL or distinguish patients with significant fibrosis. Moreover, more than half of the patients with non-significant fibrosis have a qHBsAg level greater than 1000 IU/mL.

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.

The value of intraoperative percutaneous aspiration of the mucocele of the gallbladder for safe laparoscopic management.

Mucocele of the gallbladder is an overdistended gallbladder filled with mucoid content. It is under-reported in humans, and literature review showed insufficient data about the incidence and the factors affecting the laparoscopic management. We aim to evaluate the intraoperative aspiration of the mucoid contents of the gallbladder as a factor influencing the outcome of the treatment. A prospective cohort database analysis of the results of patients who were diagnosed as mucocele of the gallbladder and treated laparoscopically between January 2003 and December 2012 was done. Diagnostic results, ultrasound findings, operative diagnosis, duration of symptoms, length of hospitalization, and complications were analyzed. 57 patients were diagnosed with mucocele of the gallbladder. The incidence rate was 5.85%. Male to female ratio was 1:1.48 and the mean age of patients was 37.41 ± 7.12 years. Ultrasound suspected mucocele in 24 (42%) patients. Laparoscopic cholecystectomy was performed in all 57 (100%) patients, and aspiration of mucoid fluid was done to all. Aspiration of the mucocele contents intraoperatively as a factor for safe laparoscopic management of mucocele of the gallbladder was found to represent a significant difference statistically (P  =  0.02). Morbidity and mortality rates were recorded as zero (0%). Laparoscopic cholecystectomy could efficiently manage mucocele of the gallbladder with morbidity and mortality rates as low as 0%. The most important factor influencing the success of the procedure is the intraoperative aspiration of the mucoid contents of the gallbladder. Collapsing of the gallbladder wall was a keystone in the non-complicated laparoscopic procedure.

Clinical patterns of postcholecystectomy syndrome.

BACKGROUNDS/AIMS: Postcholecystectomy syndrome represents a heterogeneous group of symptoms and findings in patients who have previously undergone cholecystectomy. It is rare and under-reported in Saudi Arabia. It can be attributed to many complications such as bile duct injury, biliary leak, retained common bile duct stones, recurrent bile duct stones, and bile duct strictures. In this study, we aimed to analyze the causes and evaluate the approach to postcholecystectomy syndrome in our local Saudi Arabian community because of the vast number of cases encountered in our hospital for gallbladder clinical conditions and its related complications. METHODS: A prospective cohort database analysis of 272 patients who were diagnosed and treated for postcholecystectomy syndrome between January 2000 and December 2013 were reviewed. RESULTS: The incidence rate of postcholecystectomy syndrome was 19.8%. The male to female ratio was 1:1.45. The mean age was 37.41±7.12 years. The most common causes were as follows: No obvious cause in 50 (18.4%) patients, Helicobacter pylori infection in 43 (15.8%), pancreatitis in 42 (15.4%), peptic ulcer disease in 41 (15.1%), recurrent common bile duct (CBD) stone in 26 (9.6%), retained CBD stone in 22 (8.1%), bile leakage in 19 (7%), stenosis of the sphincter of Oddi in 12 (4.4%), cystic duct stump syndrome in 11 (4%), and CBD Stricture in 5 (1.8%). The mortality rate was 0%. CONCLUSIONS: Any clinical presentation of postcholecystectomy should not be underestimated and be thoroughly investigated. Multidisciplinary collaboration is crucial for the best outcome and a safe approach for all the patients.

Mirizzi syndrome: necessity for safe approach in dealing with diagnostic and treatment challenges.

BACKGROUNDS/AIMS: The challenging dilemma of Mirizzi syndrome for operating surgeons arises from the difficulty to diagnose it preoperatively, and approximately 50% of cases are diagnosed intraoperatively. In this study, we analysed the effectiveness of diagnostic modalities and treatment options in our series of Mirizzi syndrome. METHODS: Patients had a preoperative or intraoperative diagnosis of Mirizzi syndrome, and were classified into three groups: Group 1: Incidental finding of Mirizzi syndrome intraoperatively (n=34). Group 2: Patients presented with jaundice, diagnosed by endoscopic retrograde cholangiopancreatography (n=17). Group 3: Patients diagnosed initially by ultrasound (n=13). Laparoscopic cholecystectomy was conducted in all 49 patients with Cendes type I disease. Partial cholecystectomy, common bile duct exploration, repair of fistula and t-tube placement was conducted on eight patients with Cendes type II and five patients with Cendes type III. Partial cholecystectomy with Roux-en-Y hepaticojejunostomy was conducted in two patients with Cendes type IV disease. RESULTS: Sixty-four patients were diagnosed with Mirizzi syndrome. Morbidity rate was 3.1%. Mortality rate was 0%. Group 3 (patients diagnosed initially by ultrasound) had the best treatment outcome, the least morbidity, and the shortest hospital stay. CONCLUSIONS: Suspected cases of Mirizzi syndrome should not be underestimated. Difficulty in establishing preoperative diagnosis is the major dilemma. As it is mostly encountered intraoperatively, the approach should be careful and logical to identify the correct type of Mirizzi by a thorough diagnostic laparoscopy and thus, provide optimum treatment for the subtype to achieve the best outcome.