Normal ALT Research Articles

The effect of Favipiravir on liver enzyme among patients with mild to moderate COVID-19 infection: A prospective cohort study.

Teratogenicity and hyperuricemia are considered as the major adverse effects of favipiravir, but less is known about other possible side effects which includes drug-induced liver damage and renal injury. In the current research, assessment of favipiravir-induced liver injury was performed by evaluating liver enzymes among patients with mild to moderate COVID-19 infection. A prospective cohort study was conducted on 66 patients diagnosed with mild to moderate COVID-19 infection who were treated with favipiravir for 5 days. During this period, a baseline assessment of liver enzymes (aspartate aminotransferase - AST, alanine transaminase - ALT and alkaline phosphatase - ALP) in addition to bilirubin before initiation of therapy and after 1 day of completion of therapy were carried out. The comparison of all measured parameters among all patients before and after receiving the treatment showed that non-significant differences were obtained in their levels. It was noticed that COVID-19 patients demonstrated high AST levels in which only 16 patients out of the all-subjected cases (66 patients) had AST levels of less than 45 U/L whereas the majority of patients showed normal ALT, ALP, and bilirubin levels. It was concluded that 5 days administration of favipiravir in mild to moderate COVID-19 patients who had no previous liver diseases did not affect the liver enzymes significantly and only transient elevations were occurred.

Factors Affecting the Self-Isolation Monitoring Program for COVID-19 Patients at the Universitas Indonesia Hospital.

When the outbreak of the COVID-19 delta variant occurred in June 2021, there was a marked increase in Indonesia's number of self-isolated patients. The Universitas Indonesia Hospital provided a One-Stop Service (OSS) to monitor COVID-19 patients on self-isolation. This study was conducted to determine the effectiveness of the self-isolation monitoring performed by hospitals and the factors that determined the outcomes of patients on self-isolation. This study was conducted using a cross-sectional method based on secondary data from electronic medical records. Data analysis was performed by determining the relationship of patient risk factors and characteristics with COVID-19 outcomes. The study found that poorer symptoms, administration of antibiotics, absence of shortness of breath, and normal ALT levels significantly improved the outcome of OSS patients. The study also suggested that during monitoring of patients on COVID-19 self-isolation, chest/thorax radiography is necessary. The self-isolation monitoring program is essential to observe the patient's condition and evaluate the possibility of deteriorating conditions that could lead to admission decisions in the early or middle stages of the program. This will be beneficial during pandemic emergencies.

Sero-prevalence and Associated Complications of Hepatitis B Virus Infected Patients of Khyber Pakhtunkhwa

Background: Hepatitis B infection is among the most significant public health challenge worldwide. The prevalence of HBV infection is common among most populations in Peshawar, including pregnant women. Objective: The present study aims to estimate the prevalence and complications associated with clinical parameters and risk factors in patients with HBV. Methodology: A total 150 patients were reported and subjected to Enzyme linked assay (ELISA) for HBeAg test and HBs-Ag by immunochromaticgraphic assay (ICT). RT-PCR assay was used for detection of HBV DNA load. A study designed Performa was used for face-to-face interview to collect data from the study participants. Results: According to our study, highest prevalence was found in Peshawar 34% and the second highest prevalence in Waziristan 20.2%. The results showed highest prevalence in male (54%) than female (46%) and amongst female patients, 10% were pregnant. According to patient’s age, the highest prevalence was found group 26-35 years 34.2% and lowest prevalence was <= 15 years 2.6%. In our study patients were reported on the base of antigen were 94 (62.7%) of patients with HBsAg positive and 56 HBeAg positive (37.3%). Among total patients, 5.3% were co-infected with HCV and no patients were observed co-infected with HDV or HIV. In current study, the prevalence of family affected on the base of relation was found with 21.3%, amongst these 9.3% (spouse affected), 2.7% (mother affected), sibling affected patients (4%) and children affected (5.3%) were observed. The data showed patients with normal ALT 81.3% and 18.7% with elevated and the patients 9.4% and 90.6% found with elevated and normal creatinine level respectively. The normal bilirubin (93.3%), raised bilirubin (6.7%), normal ultrasound (83.7%) and 16.3% dysfunction ultrasound were reported in patients after antiviral drugs treatment. The study surveyed 64% and 36% patients reported under tenofovir and entecavir treatment with different duration and 36%. The less mortality rate of patients leading HBV infection was reported 1.3% in this study due to renal failure and diabetics. Conclusion: The male are more exposed to the environment and that is why highest frequency infected as compared to the female. The main reason of high HBV prevalence was less awareness in people and highest prevalence on the base of family history in spouse because may close contact. Keywords: HBV,Elisa, ICT, virus , antviral

906. Characteristics of Chronic Hepatitis B Patients with Severe Outcomes in a Large Integrated Healthcare System - 2008-2019

BackgroundIt is estimated that there are 1.59 million cases of chronic hepatitis B virus (HBV) infection (CHB) in the United States. HBV infection is highest among men and non-Hispanic Asian adults. CHB can lead to liver damage, cirrhosis, hepatocellular carcinoma, or death. However, the population that is most likely to develop severe outcomes is not as well-defined.MethodsWe evaluated electronic health record data from Kaiser Permanente Southern California adult members from 2008-2019 with at least 1 year of continuous membership, and with 2 successive, positive HBV lab results (HBV DNA, or HBsAg, or HBeAg) at least 6 months apart (indicative of CHB). Severe outcomes included incident hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant and death, and prevalent and incident liver cirrhosis. For each outcome, we estimated the distribution of characteristics including age, sex, race/ethnicity, and lab values (alanine aminotransferase [ALT], alpha-fetoprotein [AFP], MELD score).ResultsOur final study population included 5,427 CHB-diagnosed patients with 411 (7.6%) cases of liver cirrhosis, 123 (2.3%) of hepatic decompensation, 65 (1.2%) of HCC, 8 (0.1%) of liver transplant, and 164 (3.0%) deaths. Compared to the total cohort, those who developed severe outcomes were older (median age for each outcome >50 years vs. 47 years in total CHB population). Among those with severe outcomes, the majority were male ( >56%) and Asian. Diabetes was more prevalent in patients with hepatic decompensation, HCC, and death versus the entire cohort (25% vs. 8%, respectively, P< 0.0001), and twice as prevalent among those with cirrhosis. All severe outcomes were associated with >2 x upper limit of normal ALT levels. ConclusionThe characteristics of those with severe outcomes were consistent with those of overall CHB, although there was a 2-3 times higher prevalence of diabetes in those with severe outcomes. Identifying characteristics that are more prevalent in those with severe outcomes can help inform screening and management of CHB.Disclosures Ana Florea, PhD MPH, Gilead Inc. (Grant/Research Support) Prabhu Gounder, MD, Gilead Inc. (Grant/Research Support) Amandeep Sahota, MD, MS, Gilead Inc (Grant/Research Support) Katherine J. Pak, MS, Gilead (Grant/Research Support) Vennis Hong, MPH, Gilead Inc. (Research Grant or Support) Theresa M. Im, MPH, Gilead Inc. (Grant/Research Support) Sara Tartof, PhD, Gilead (Grant/Research Support, Scientific Research Study Investigator)

Distinct Bile Acid Profiles in Patients With Chronic Hepatitis B Virus Infection Reveal Metabolic Interplay Between Host, Virus and Gut Microbiome.

Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications.Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis.Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients.Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.

S2409 Histoplasmosis Presenting as New-Onset Ascites in a Crohn’s Disease Patient on Adalimumab

Introduction: Histoplasma capsulatum is the most frequently diagnosed endemic mycosis in the United States. The majority of cases are self-limiting but infections in immunocompromised patients may result in severe pulmonary or disseminated disease. We report a rare case of disseminated histoplasmosis presenting as new- onset ascites due to granulomatous hepatitis in a patient with perianal Crohn’s Disease on Adalimumab. Case description/methods: A 39-year-old white female with perianal but no intraluminal Crohn’s Disease currently on adalimumab and azathioprine presented with cyclical fevers and rapid onset ascites. In the preceding weeks she was noted to have uptrending alkaline phosphatase (600s) with isoenzymes consistent with liver etiology, GGT 162, mildly elevated AST (53) with normal ALT and total bilirubin. Further workup included positive anti-smooth muscle (1:160) and F-actin antibodies. Anti-nuclear and anti-mitochondrial antibodies both returned negative. MRCP demonstrated a circumferential 1.9 x 1.3cm peribiliary mass with segmental biliary duct dilation. Paracentesis with peritoneal fluid analysis demonstrated a low serum-ascites albumin gradient, lymphocytic predominance, and negative cytology, acid-fast stain, tuberculosis PCR, and adenosine deaminase. Transjugular liver biopsy revealed multiple non-necrotizing granulomas surrounded by chronic inflammation, consisting predominantly of lymphocytes and eosinophils. Grocott’s methenamine sliver stain was positive for narrow-based budding yeast, with morphology suggestive of Histoplasma species. Additionally, a quantitative serum Histoplasmosis antigen returned positive at 2.53 ng/ml. Following these findings, a course of IV Amphotericin B was started with eventual transition to PO Itraconazole for 1 year. Discussion: Histoplasmosis capsulatum is a dimorphic fungus that is endemic to the United States, specifically the Ohio and Mississippi River valleys. The majority of infections are subclinical, but when diagnosed are primarily in immunocompromised patients. A high degree of clinical suspicion is required to facilitate early treatment and prevent poor outcomes. Pulmonary histoplasmosis is by far the most common clinical presentation. Progressive disseminated disease is rare, but may involve the liver, skin, adrenals, gastrointestinal tract, central nervous system, and bone marrow. With the use of immunomodulating therapies on the rise, it is important to consider opportunistic infections in patients with atypical presentations.Figure 1.: A: H&E staining at 200x magnification of liver biopsy demonstrating non-caseating granulomas. B: Liver biopsy shows narrow-based budding yeast with positive silver stain suggestive of Histoplasma.

S1127 Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) in Virally Suppressed Chronic Hepatitis B (CHB) Patients With Renal Impairment: Week 48 Results From a Phase 2 Open-Label Study

Introduction: Switching to TAF, a novel tenofovir prodrug, has shown maintenance of viral suppression with stable or improved bone and renal safety at Week 24 in CHB patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault [eGFRCG] < 60 mL/min) and ESRD patients on HD. We evaluated the safety and efficacy in these virally suppressed patients with renal impairment 1 year after switching to TAF in a Phase 2 study. Methods: CHB patients with renal impairment receiving TDF and/or other OAVs for ≥48 weeks and virally suppressed for ≥6 months with HBV DNA < 20 IU/mL at screening were enrolled into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG 15 to < 60 mL/min) and 2) ESRD (eGFRCG < 15 mL/min) on chronic HD. All patients were switched to TAF 25 mg QD for 96 weeks (given post-HD on days of dialysis for ESRD patients). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed in all patients at Week 48. Results: 93 patients (moderate-severe impairment 78; ESRD 15) were enrolled from 26 sites in 8 countries; 89% of patients remained on study at Week 48. At baseline, 74% were male, 77% Asian, 68% ≥60 y, 83% HBeAg-negative and median ALT was 17 U/L. Up to 25% overall (both cohorts) had osteoporosis at hip and/or spine, and a high proportion had comorbidities (60% HTN, 24% DM). Key efficacy/safety results at Week 48 are summarized in the Table. Efficacy (HBV DNA< 20 IU/mL) was maintained in nearly all patients on treatment at Week 48 and a high proportion had normal ALT levels. Five patients discontinued study drug early (withdrew consent) with last available HBV DNA < 20 U/mL; 1 patient had HBV DNA ≥20 IU/mL and 1 patient died. Relative to baseline levels, switching to TAF resulted in stable hip/spine BMD in moderate to severe renal impairment patients, with a slight decrease in hip BMD in ESRD patients. Slight improvements were observed in renal parameters including eGFRCG and markers of renal tubular function in moderate to severely impaired patients. TAF was well tolerated, with no Grade 3/4 or serious adverse events related to study drug. Conclusion: In renally-impaired CHB patients, including ESRD patients on HD, viral suppression was well maintained, and the bone and renal safety were stable or improved 48 weeks after switching to TAF.Table 1.: Study outcomes comparing EUS-guided liver biopsy and percutaneous liver biopsy.

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3months and all within 1year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Role of hepatosteatosis in HBsAg seroconversion in HBeAg-negative chronic hepatitis B patients.

In chronic Hepatitis B virus (HBV) infection, certain individual and viral characteristics such as advanced age, presence of hepatic steatosis (HS), normal ALT levels, initially negative HBeAg and HBV DNA, and genotype of the virus are associated with HBsAg seroclearance and seroconversion. Herein, we report the results of our study evaluating the association between hepatosteatosis and HbsAg seroconversion. The clinical and biochemical data of patients with CHB and hepatosteatosis (HS) (HBsAg seroconversion, n:52, and non-HbsAg seroconversion, n:352), and the rate of development of HBsAg seroconversion were evaluated. We collected data from 404 patients with HBeAg negative CBH (mean age ± SD: 36.2±11years; 223 [55.2%] men, 181 [44.8%] women). The mean age at diagnosis of disease was 36.2±11years. The mean duration of the disease was 10.6±7years. Seroconversion developed in 52 patients (12.8%) with serum HBsAg positive (mean ± SD: 12.7±5.8). Elderly age and the duration of disease time were significantly associated with seroconversion (P<.001). The presence of serum HBsAg seroconversion was significantly associated with hepatosteatosis (OR: 3.06, 95% CI 1.64-5.71, P<.01). Serum HBsAg seroconversion was more frequent in patients with mild HS than patients with moderate-severe HS (P=.04). In multivariate regression analysis, the presence of HS was found to be an independent factor predicting the development of HBsAg seroconversion (OR: 2.07 95% GA:1.07-4.0 P=.03). The presence of mild HS in HBeAg negative chronic hepatitis B patients contributes to HBsAg seroconversion. Further studies are required to better understand the relationship between steatosis and HBsAg seroconversion.

Association Analysis of Genetic Variants of Sodium Taurocholate Co-Transporting Polypeptide NTCP Gene (SLC10A1) and HBV Infection Status in a Cohort of Egyptian Patients

Background: Single nucleotide polymorphisms (SNPs) in the SLC10A1 gene, coding for a functional receptor of hepatitis B virus (HBV), sodium taurocholate co-transporting polypeptide (NTCP), may influence the susceptibility, outcome, and disease course of HBV infection in some populations. Aim: to determine the prevalence of SNPs of the NTCP gene, rs2296651 and rs943277, and their relationship with chronic HBV infection in a group of Egyptian patients. Methods: One hundred and thirty seven patients with HBV and 65 healthy controls were enrolled, and the patients were divided into two groups; group I chronic HBV infection (68 patients with normal ALT and minimal or no liver necroinflammation or fibrosis) and group II chronic hepatitis B (69 patients with elevated ALT and moderate or severe liver necroinflammation). They were subjected to full history taking, clinical examination, laboratory investigations, abdominal ultrasound, and liver stiffness measurement using both Echosens® Fibroscan and acoustic radiation force impulse (ARFI). A real time PCR TaqMan 5′ allelic discrimination assay was applied to detect the SNPs in the NTCP gene, rs2296651 and rs943277. Results: On studying the rs2296651 variant, all controls and patients had genotype GG without any significant association with HBV infection or disease progression. However, the rs943277 variant in all controls and 98% of patients had genotype GA, except for two chronic HBV infection patients who had genotype AA, but no significant difference between patients and controls was found. The non-invasive methods for liver fibrosis assessment ARFI, AST/platelet’s ratio (APRI), and fibrosis-4 score (FIB-4) could predict the stages of fibrosis in agreement with Fibroscan with AUCOR 0.8, 0.79, and 0.76, respectively. Conclusion: These findings may suggest that there is no relation between these SNPs of the NTCP gene and the susceptibility or chronicity of HBV infection in the Egyptian population. We also suggest that the use of the non-invasive methods for liver fibrosis assessment, ARFI, FIB-4, and APRI, may decrease the need for liver biopsies in the prediction of significant hepatic fibrosis in chronic HBV patients.

Antiviral Therapy for Chronic HBV Infection With Persistently Normal Alanine Aminotransferase: Controversy and Consensus.

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state. A considerable number of patients will develop active hepatitis or occult progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, whether antiviral therapy should be recommended for chronic HBV infection with normal ALT level has been a hot topic in clinical practice. In this paper, the definition of immune tolerance, the relationship between ALT and liver inflammation, and the benefits of antiviral therapy were reviewed, and we hope it will be helpful for clinicians to have a deeper understanding of whether antiviral therapy should be considered for chronic HBV infection with normal ALT.

"Treat All" is not recommended in chronic HBV infection patients with normal ALT

"Treat All" is not recommended in chronic HBV infection patients with normal ALT

Review of Clinical Guidelines in the Diagnosis of Pediatric Nonalcoholic Fatty Liver Disease.

Review of Clinical Guidelines in the Diagnosis of Pediatric Nonalcoholic Fatty Liver Disease.

Diagnostic Accuracy of Serum Hyaluronan for Detecting HCV Infection and Liver Fibrosis in Asymptomatic Blood Donors.

Background: The disease caused by hepatitis C virus (HCV) is asymptomatic, silent, and progressive liver disease. In HCV-infected patients the increase in serum HA is associated with the development of hepatic fibrosis and disease progression. Methods: HCV-RNA detection was performed in all serological samples of blood donors that tested positive using HCV Ultra ELISA. Determination of hyaluronan (HA) was performed in positive HCV samples using ELISA-like fluorometric method. The HA content was compared to HCV viral load, genotype of the virus, liver fibrosis as well as ALT and GGT liver biomarkers. Results: Persistently normal ALT (<40 U/L) and GGT (<50 U/L) serum levels were detected in 75% and 69% of the HCV-Infected blood donors, respectively. Based on ROC analysis, the HA value < 34.2 ng/mL is an optimal cut-off point to exclude HCV viremia (specificity = 91%, NPV = 99%). Applying HA value ≥34.2 ng/mL significant liver fibrosis (≥F2) can be estimated in 46% of the HCV-infected blood donors. HA serum level (≥34.2 ng/mL) associated with a high ALT level (>40 U/mL) can correctly identify HCV infection and probable liver fibrosis (sensitivity = 96% and specificity = 90%) in asymptomatic blood donors. Conclusions: A high level of HA (≥34.2 ng/mL) in association with ALT (≥40 U/L) in serum can provide a good clinical opportunity to detect HCV-infected asymptomatic persons that potentially require a liver biopsy confirmation and antiviral treatment to prevent the development of advanced liver fibrosis or cirrhosis.

Histological activity despite normal ALT and IgG serum levels in patients with autoimmune hepatitis and cirrhosis

Background & AimsIn autoimmune hepatitis (AIH), normal levels of transaminases and IgG define biochemical remission and are considered the best surrogate markers for histological remission. This study assessed whether this also applies to patients with AIH cirrhosis.MethodsIn this European multicentric study, we included 125 biopsies from 113 patients with AIH and histologically proven cirrhosis; 105 biopsies from 104 patients with AIH without cirrhosis served as controls. Biochemical parameters were available within 4 weeks of biopsy. AIH activity was graded according to the modified Hepatitis Activity Index (mHAI), with mHAI ≥4/18 considered to indicate risk of disease progression.ResultsIn total, 47 out of 125 liver biopsies were obtained from patients with AIH cirrhosis and normal ALT levels at time of biopsy. Only 26% (12/47) of those livers showed histological remission (mHAI <4/18), whereas 36% (17/47) showed moderate to high histological activity (mHAI ≥6/18). In patients with noncirrhotic AIH, 88% (46/52 biopsies) of cases with normal ALT levels had histological remission and only 4% (2/52) had an mHAI ≥6/18 (p <0.001). The addition of IgG to define complete biochemical remission only slightly improved the association with histological remission in the limited number of patients with AIH cirrhosis available for analysis [29% (5/17) of biopsies with mHAI <4/18]. ALT correlated closely with mHAI in AIH without cirrhosis but poorly in AIH with cirrhosis.ConclusionsIn contrast to patients with noncirrhotic AIH, in patients with AIH cirrhosis, who are at risk of disease progression, normal ALT levels and potentially also complete biochemical remission are poor surrogate markers of histological remission. Thus, new biomarkers are needed to monitor disease activity and progression in patients with AIH cirrhosis.Lay summaryAutoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually responds to immunosuppressive therapy. Serum transaminases and IgG levels within the normal ranges define complete biochemical remission and are considered as surrogate markers for histological disease activity. Here, we show that those biochemical markers are not sufficient to indicate low disease activity in patients with AIH and already established cirrhosis. Consequently, until better biomarkers for disease activity are found, only liver biopsy can reliably indicate disease activity in the presence of cirrhosis. Additional investigations, such as measurements of liver stiffness, should be undertaken to monitor non-invasively for disease progression in patients with AIH and established cirrhosis.

Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life.

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex® ) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real-life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2mg/d in subcutaneous injection) and pegylated interferon (PEG-IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1log10 and 3/3 of 2log10 of HDV-VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV-VL relapse was notified 24weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV-VL during the therapy (<100IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV-VL by 1log10 at 8 weeks and 1/1 by 2log10 at 28 week on-treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long-term clinical benefit (fibrosis reversibility and reduction in hepato-cellular carcinoma [HCC]).

The needs of surveillance of metabolic associated fatty liver disease in Taiwan

The needs of surveillance of metabolic associated fatty liver disease in Taiwan

Modelling the cost effectiveness of non-alcoholic fatty liver disease risk stratification strategies in the community setting.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Identifying high-risk patients is critical to best utilize limited health care resources. We established a community-based care pathway using 2D ultrasound shear wave elastography (SWE) to identify high risk patients with NAFLD. Our objective was to assess the cost-effectiveness of various non-invasive strategies to correctly identify high-risk patients.MethodsA decision-analytic model was created using a payer’s perspective for a hypothetical patient with NAFLD. FIB-4 [≥1.3], NAFLD fibrosis score (NFS) [≥-1.455], SWE [≥8 kPa], transient elastography (TE) [≥8 kPa], and sequential strategies with FIB-4 or NFS followed by either SWE or TE were compared to identify patients with either significant (≥F2) or advanced fibrosis (≥F3). Model inputs were obtained from local data and published literature. The cost/correct diagnosis of advanced NAFLD was obtained and univariate sensitivity analysis was performed.ResultsFor ≥F2 fibrosis, FIB-4/SWE cost $148.75/correct diagnosis while SWE cost $276.42/correct diagnosis, identifying 84% of patients correctly. For ≥F3 fibrosis, using FIB-4/SWE correctly identified 92% of diagnoses and dominated all other strategies. The ranking of strategies was unchanged when stratified by normal or abnormal ALT. For ≥F3 fibrosis, the cost/correct diagnosis was less in the normal ALT group.ConclusionsSWE based strategies were the most cost effective for diagnosing ≥F2 fibrosis. For ≥F3 fibrosis, FIB-4 followed by SWE was the most effective and least costly strategy. Further evaluation of the timing of repeating non-invasive strategies are required to enhance the cost-effective management of NAFLD.

Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone.

A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the 'grey zone (GZ)'. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty-nine consecutive treatment-naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106 IU/ml (GZ-A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2×104 IU/ml (GZ-B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2×103 IU/ml (GZ-C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2×103 IU/ml (GZ-D). The distributions of different immune states were: 233 (4.90%) patients in immune-tolerant phase, 941 (19.77%) patients in HBeAg-positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg-negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ-B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg-positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ-B had advanced fibrosis or even cirrhosis.

The frequency of non-alcoholic fatty liver disease in non-obese young medical professionals.

This cross-sectional study was conducted in Mayo Hospital, Lahore, from July 16, 2018 to January 15, 2019 to observe the frequency of occurrence of non-alcoholic fatty liver disease in non-obese young medical professionals. One hundred and fifty-three subjects were selected using Simple Random Sampling Technique. SPSS version 25.0 was used to analyse the data. Out of a total of 153 medical professionals, 67 (43.8%) were males and 86 (56.2%) were females, median age was 23 years (inter-quartile range of 5 years), mean BMI was 22.79 ± 1.57 kg/m2, 122 (79.7%) subjects had normal texture of liver on ultrasonography and normal ALT levels, 21 (13.7%) had fatty liver with normal ALT levels, and 10 (6.5%) had fatty liver and elevated ALT levels (NASH). NAFLD and NASH are common ultrasonographic findings in seemingly healthy young adults with normal BMI. Awareness programmes should be carried out at the national level to educate the general public about the prevention and treatment of this disease through lifestyle and dietary modifications.