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.

Clinical and virological outcomes of entecavir therapy in patients with chronic hepatitis B: A real life experience.

BACKGROUND: Entecavir (ETV) is a nucleoside analogue (NA) that is effective for treatment of chronic hepatitis B (CHB) due to its low resistance rates and potent antiviral effects. We aimed to evaluate the clinical, biochemical and virological response to ETV in patients without a prior use of nucleos(t)ide (NA-naïve) vs. those who failed prior NA use (NA-experienced) in the treatment of CHB. METHODS: Patients treated between April 2012 and December 2017 were retrospectively studied. A comparison was made between patients treated with ETV in NA-naïve Vs. NA-experienced. Complete virological response (CVR) was defined as achieving undetectable HBV-DNA level, up to 15 IU/ml, partial virological response (PVR) as 15-200 IU/ml and >200 IU/ml for no virological response (NVR) after one year of therapy. RESULTS: Overall, 148 patients were included (69 NA-naïve and 79 NA-experienced). In NA-naïve group, 51%, 17% and 32% achieved CVR, PVR and NVR vs. 17%, 9% and 75% in NA-experienced group, respectively (p < 0.001). HBsAg seroconversion was achieved in 5.8% in NA-naïve group vs. 6.3% in NA-experienced group (p = 1.00). HBeAg seroconversion was 17% in NA-naïve group and 25% in NA-experienced group (p = 0.24). There was no significant difference in alanine transaminase normalization or in mortality rate between both groups; p = 0.87 and p = 1.00 respectively. CONCLUSION: ETV therapy in CHB results in a better virological response in NA-naïve patients compared to NA-experienced. There were no differences between both groups in regards to the rate of HBsAg or HBeAg seroconversions, biochemical improvements or mortality.

Acute onset autoimmune hepatitis: Clinical presentation and treatment outcomes.

INTRODUCTION AND AIM: Autoimmune hepatitis (AIH) may present acutely, which can rapidly progress to fulminant type. This pattern has been described worldwide but is generally under-reported. We aim to describe the clinical presentation and treatment outcomes of patients with acute onset AIH. MATERIALS AND METHODS: A multicenter retrospective cohort study of patients with acute onset AIH. Clinical, biochemical, and histological data were analyzed and the outcomes were reported. RESULTS: Seventy patients were included. The mean age was 33.8±1.5 years and 58.6% were female. Upon initial presentation, 94% had jaundice, 44% had fatigue, 31% had pruritus, and 29% had abdominal pain. Biochemical analysis revealed elevated alanine transaminase (733±463.6), aspartate transaminase (699±423), and total bilirubin (210±181.8). Antinuclear antibody (ANA) was positive in 61% of patients, anti-smooth muscle antibody (ASMA) in 69%, and both in 31%; immunoglobulin G (IgG) was elevated in 86% of patients. Advanced fibrosis was found in 39%. Complete remission was achieved in 74.3%, two patients required liver transplants and six died. No specific biomarkers were identified as predictive of remission; however, advanced age was associated with poor prognosis. CONCLUSION: Acute onset AIH is a disease that requires early diagnosis and management. We confirmed that elevated transaminases are the hallmark of biochemical presentation of acute AIH. High IgG, ANA and ASMA are typically present in such patients upon presentation, however, their absence does not totally exclude the diagnosis. Initial response to treatment was excellent; however, the long-term mortality was higher than the general patient population.

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.

Serum procalcitonin in cirrhotic patients with septic shock: relationship with adrenal insufficiency and clinical outcomes.

BACKGROUND: Serum procalcitonin is commonly used to differentiate systemic inflammation due to infection from non-infectious causes. Limited data exist on the value of procalcitonin in predicting relative adrenal insufficiency (RAI). This study evaluated the value of procalcitonin in predicting RAI and mortality in cirrhotic patients with septic shock. METHODS: This was a post-hoc analysis of a randomized placebo-controlled trial that evaluated low-dose hydrocortisone in cirrhotic patients with septic shock. Extracted first study-day data included serum procalcitonin, baseline serum cortisol, cortisol level after 250 microg - adrenocorticotropic hormone stimulation test and 28 - day mortality. RAI was defined as a baseline serum cortisol < 10 microg/dL or cortisol not rising by > 9 microg/dL after stimulation. Procalcitonin > 0.5 ng/mL was considered high. RESULTS: Forty-five patients had serum procalcitonin measured (mean = 2.7 +/- 3.2 ng/mL, first and third quartiles were 0.3 and 3.3 ng/mL, respectively). Most (78%) patients had high procalcitonin levels. RAI was present in 34 (76%) patients. Patients with high procalcitonin were more likely to have RAI (odds ratio, 4.8; 95% confidence interval, 1.1 - 22.1). Receiver operator characteristic curve analysis showed that the best cut-off for detecting RAI was 1.0 ng/mL (sensitivity = 79% and specificity = 55%). High serum procalcitonin was not associated with 28 -day mortality (80% for normal procalcitonin and 77% for high procalcitonin, p = 0.61). CONCLUSIONS: High serum procalcitonin was highly associated with RAI in cirrhotic patients with septic shock. Procalcitonin was not associated with 28 - day mortality in this patient population.

Clinical Presentations and Risk Factors of Gastrointestinal Bleeding in the Emergency Department: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Gastrointestinal bleeding is a major healthcare burden and is associated with significant morbidity and mortality. This study aimed to assess the prevalence, clinical presentation, and risk factors of patients presenting with gastrointestinal bleeding in the emergency department. MATERIALS AND METHODS: This retrospective study was conducted in two tertiary care hospitals in Riyadh, Saudi Arabia. The medical records of patients who presented to the emergency department with gastrointestinal bleeding between January 2010 and January 2020 were reviewed. Patients aged 18 years or older, with gastrointestinal bleeding (upper or lower) regardless of underlying cause, lifestyle, location of bleeding, health status, or medication use, were included. Demographic characteristics, initial vital signs, medical history, physical examination findings, comorbidities, medications, laboratory and radiological investigations, cause and stage of liver disease, management, and complications were recorded. Endoscopic findings and management of the bleeding site were collected according to the presenting symptoms. RESULTS: A total of 760 patients were included. The mean age was 62.7 ± 17.8 years, and 61.4% were males. The most common comorbidities at presentation were hypertension (54.1%), diabetes mellitus (51.2%), and ischemic heart disease (18.2%). The origins of the bleeding were lower gastrointestinal in 52% and upper gastrointestinal in 48% of patients. CONCLUSIONS: Lower gastrointestinal bleeding was found to be more common than upper gastrointestinal bleeding. Hemorrhoids, polyps, diverticular disease, and colonic ulcers were the major risk factors for lower gastrointestinal bleeding. In contrast, upper gastrointestinal bleeding was predominantly caused by esophageal varices, gastritis, and peptic ulcers.

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.

Pegylated versus standard interferon plus ribavirin in chronic hepatitis C genotype 4: A systematic review and meta-analysis.

AIM: Treatment of hepatitis C genotype 4 (HCV-G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta-analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR). METHODS: We searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta-analysis was used to pool the risk ratio (RR) of achieving SVR across trials. RESULTS: Five RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR = 1.51, 95% confidence interval [CI] = 1.08-2.10). SVR was significantly higher in PEG IFN-α-2a compared to the -α-2b group (P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR (P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity. CONCLUSION: In treatment-naive patients with HCV-G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.

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.

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.).

The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients.

BACKGROUND: Cirrhotic patients are characterized by a decreased synthesis of coagulation and anticoagulation factors. The coagulopathy of cirrhotic patients is considered to be auto-anticoagulation. Our aim was to determine the incidence and predictors of venous thromboembolism (VTE) and examine the practice of deep venous thrombosis (DVT) prophylaxis among hospitalized cirrhotic patients. METHODS: A retrospective cohort study was performed in a tertiary teaching hospital. We included all adult patients admitted to the hospital with a diagnosis of liver cirrhosis from January 1, 2009 to December 31, 2009. We grouped our cohort patients in two groups, cirrhotic patients without VTE and cirrhotic with VTE. RESULTS: Over one year, we included 226 cirrhotic patients, and the characteristics of both groups were similar regarding their clinical and laboratory parameters and their outcomes. Six patients (2.7%) developed VTE, and all of the VTEs were DVT. Hepatitis C was the most common (51%) underlying cause of liver cirrhosis, followed by hepatitis B (22%); 76% of the cirrhotic patients received neither pharmacological nor mechanical DVT prophylaxis. CONCLUSION: Cirrhotic patients are at risk for developing VTE. The utilization of DVT prophylaxis was suboptimal.

Etomidate and mortality in cirrhotic patients with septic shock.

BACKGROUND: Clinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone. METHODS: This is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome. RESULTS: Sixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality. CONCLUSIONS: In this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.

Uveitis and autoimmune hepatitis, a real entity? A case report with review of the literature.

A 63-year-old man presented with a 10-day history of severe pain, redness of the right eye, and reduced vision in both eyes. In addition, he had been diagnosed incidentally with liver cirrhosis and splenomegaly 1 week before he was admitted to our center. The patient was found to have severe intraocular inflammation that initially involved the right eye and then progressed to bilateral panuveitis. The presenting visual acuity was 20/60 for the left eye and lumbar puncture (LP) for the right eye. Vitreous tap revealed a nonturbid, yellow fluid that was negative for organism culture, polymerase chain reaction (PCR), and tumor markers. Oral prednisolone significantly improved the clinical status of both ocular and hepatic inflammation. During the admission period, the patient developed several medical comorbid complications that temporarily altered the management of our case. After a full evaluation of uveitis causes, the patient was diagnosed with biopsy-proven autoimmune hepatitis. In addition to a high-dose oral steroid, azathioprine was given for 3 months before the patient developed decompensated liver failure, which was successfully managed with a liver transplant. The patient was stable for 1 year following the transplant but eventually developed blindness of the right eye and visual acuity of 20/30 in the left eye.

Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial.

BACKGROUND: Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. METHODS: We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 µg/dL from baseline after stimulation with 250 µg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. RESULTS: The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98-2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92-1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04-6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08-8.36, p = 0.02). INTERPRETATION: Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.).

Principles of Care for Patients with Liver Disease During the Coronavirus Disease 2019 (COVID-19) Pandemic: Position Statement of the Saudi Association for the Study of Liver Disease and Transplantation.

In December 2019, a novel coronavirus was identified in patients in Wuhan, China. The virus, subsequently named severe acute respiratory syndrome coronavirus-2, spread worldwide and the disease (coronavirus disease 2019 or COVID-19) was declared a global pandemic by the World Health Organization in March 2020. Older adults and individuals with comorbidities have been reported as being more vulnerable to COVID-19. Patients with chronic liver disease (CLD) have compromised immune function due to cirrhosis and are more susceptible to infection. However, it is unclear if patients with CLD are more vulnerable to COVID-19 and its complications than other populations. The high number of severe cases of COVID-19 has placed an unusual burden on health systems, compromising their capacity to provide the regular care that patients with CLD require. Hence, it is incredibly crucial at this juncture to provide a set of interim recommendations on the management of patients with CLD during the current COVID-19 outbreak.

Hepatitis B care pathway in Saudi Arabia: Current situation, gaps and actions.

Hepatitis B virus (HBV) infection remains a public health problem worldwide. In this review, we aim to assess the current situation of the HBV care pathway in the Kingdom of Saudi Arabia (KSA), identify gaps/barriers therein, and recommend initiatives to be taken to improve the management of such patients. Towards this end, a literature search was conducted in PubMed and free Internet searches. Interviews with individuals and focus group discussions were held with HBV experts in KSA. Although significant improvements have been made in the past 30 years in KSA in terms of the decline in prevalence (currently estimated to be around 1.3%), the morbidity and mortality related to the disease have not shown a parallel decline. This makes HBV an important public health concern. Furthermore, poor disease awareness, low diagnosis rates, and nonadherence to therapy amplify the disease burden. There are several mandated national screening structures present; however, established protocols for those who test positive and subsequent linkage-to-care are inadequate. In the absence of a virologic cure, a concerted effort should be made to provide safe and effective lifelong treatment. This review provides recommendations to reduce the HBV disease burden in the Saudi population.

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.

Clinicopathologic characteristics andoutcomes of hepatocellular carcinoma associated with chronic hepatitis B versus hepatitis C infection.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver malignancy and one of the most common cancers worldwide. Few studies in Saudi Arabia have compared the clinicopathologic characteristics of HCC caused by hepatitis B virus (HBV) versus hepatitis C virus (HCV) and their effect on patient survival and prognosis. OBJECTIVES: Identify differences in clinicopathological characteristics and outcomes of hepatocellular carcinoma (HCC) caused by HBV versus HCV. DESIGN: A retrospective medical records review. SETTING: Tertiary medical center in Riyadh. PATIENTS AND METHODS: We included all new cases of HCC with underlying HBV and HCV infection diagnosed between January 2013 and September 2017 that met inclusion criteria. MAIN OUTCOME MEASURES: Clinical, biochemical, pathological and radiological characteristics, and survival differences were compared between HCC that developed in HBV- and HCV-infected patients. SAMPLE SIZE: Of 253 patients evaluated, 172 patients were included in the study. RESULTS: Of the 172 patients, 110 (64%) had HCV-associated HCC and 62 (36%) had HBV-associated HCC. More patients with HBV infection were males (P=.003) and were younger (P=.015) than HCV patients. HCV-infected patients who developed HCC had more advanced cirrhosis (P=.048). The prevalence of comorbidities and pre-existing cir.rhosis was similar in both groups. Seven patients (6.8%) with underlying HCV developed HCC in the absence of cirrhosis. Patients with HBV-associated HCC were less likely to meet Milan criteria at initial diagnosis than those with HCV-associated HCC (33.9% vs. 52.7%, respectively, P=.017). HBV-associated HCC occurred at a more advanced Barcelona Clinic Liver Cancer stage. The overall median survival and treatment outcome for each modality was comparable. CONCLUSIONS: HBV- and HCV-associated HCC have distinct clinical and pathological characteristics, necessitating different screening policies to optimize HCC surveillance and management. However, viral etiology did not affect the treatment outcome and long-term survival. LIMITATIONS: Conducted in a single-center, retrospective and lacks information about the use of antiviral treatment. CONFLICT OF INTEREST: None.

The Role of Urinary Neutrophil Gelatinase-Associated Lipocalin in Predicting Acute Kidney Dysfunction in Patients With Liver Cirrhosis.

BACKGROUND: Early detection of acute kidney dysfunction (AKD) in cirrhotic patients is crucial. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been identified as an early marker of AKD. The aim of the study was to evaluate serial uNGAL as a marker and predictor of AKD in liver cirrhosis patients. METHODS: Serial uNGAL and serum creatinine (sCr) levels were measured daily during the first 6 days of admission. Furthermore, sCr levels and the estimated glomerular filtration rate (eGFR) were measured after 3 - 6 weeks. The uNGAL levels in patients with and without abnormal sCr were compared. RESULTS: Fifty-seven consecutive cirrhotic patients were enrolled in the study. Eight of 14 patients (57%) who developed abnormal uNGAL level also had abnormal sCr level (odds ratio (OR) = 3.4, 95% CI: 0.99 - 12.03, P = 0.05). After 6 weeks, 41% of patients exhibited an abnormal uNGAL level and abnormal sCr (OR = 6.7, 95% CI: 1.55 - 28.85, P = 0.01). Area under the curve (AUROC) and the best cut-off point for highest NGAL in 6 days were 0.64 and 72.55 ng/mL, respectively. CONCLUSIONS: There is a modest association between highest uNGAL in the first 6 days of admission and sCr at week 6 in all participants. This may indicate that in cirrhotic patients, uNGAL level during the first 6 days of admission has a potential predictability for the development of high sCr and low eGFR 6 weeks later. The AUROC of 0.64 quantifies the overall ability of uNGAL to discriminate between those individuals who will have a raised sCr levels and those who will not.