Patients Underwent Liver Biopsy Research Articles

Normal transaminases in obese patients with metabolic associated steatohepatitis (MASH): a cohort of Peruvian patients

Introduction: Metabolic associated steatohepatitis (MASH) is one of the most frequent causes of chronic liver disease. Liver transaminases are important biomarkers to measure liver injury, however, a proportion of patients with MASH may present with normal levels of transaminases. The levels of serum transaminases may not correlate with the severity of histopathological changes. Objective: We aimed to identify the frequency of normal transaminases in obese patients with MASH, as well as to describe the clinical, biochemical and histological characteristics in this specific group of patients. Materials and methods: A retrospective cross-sectional study was conducted in the bariatric surgery service of a private clinic. Obese patients older than 18 years with a body mass index (BMI) >30Kg/m2 and 2 co-morbidities undergoing a gastric sleeve surgery were included. Measurement of biochemical routine laboratory exams was performed. Insulin resistance was calculated using the homeostasis evaluation model (HOMA-IR). All patients underwent liver biopsies prior to surgery and the diagnosis of MASH was based on the Brunt criteria. Results: 159 obese patients with MASH were included, of which 47.2% had normal transaminases and 52.8% elevated transaminases. Factors associated with alteration in transaminases were: being male OR=4.02 (95% CI: 2.03-7.96; p<0.01), diagnosis of type 2 diabetes mellitus OR=4.86 (95% CI: 1.97- 11.95; p<0.01) and levels of GGT >50 IU/L OR=7.50 (95% CI: 3.40-16.56; p<0.01). The values of HOMA-IR and GGT were significantly higher in the group of high transaminases (p<0.01). Differences in the degree of fibrosis were not associated with transaminases levels. Conclusion: In conclusion we found that the frequency of normal transaminases was 47.2% in obese patients with MASH. Factors associated with elevation in liver enzymes were being male, diagnosis of diabetes mellitus and elevation in GGT levels. The degree of fibrosis was not associated with elevations in liver transaminases. These findings suggest that transaminases levels alone are not accurate markers to assess liver injury, as they do not necessarily correlate with histological liver damage.

Hepatitis B core-related antigen serum levels are associated with significant liver fibrosis in treatment-naive chronic HBV infection patients.

Several hepatitis B virus (HBV) serum markers have been identified as risk factors for liver fibrosis in patients with chronic HBV infection, and several noninvasive fibrosis tests based on serum indexes are now used to identify the severity of liver fibrosis. We aimed to identify the relationship between hepatitis B core-related antigen (HBcrAg) serum levels and liver fibrosis in treatment-naive chronic HBV infection patients. A total of 246 treatment-naive chronic HBV infection patients were enrolled in this study. All of the patients underwent liver biopsies at baseline. Using the METAVIR fibrosis stages, there were 15, 140, 50, 26 and 15 patients in the F0, F1, F2, F3 and F4stages (METAVIR scoring system), respectively. The biochemical, serological and virological parameters were measured using standard laboratory procedures. The HBcrAg serum levels of the patients were examined via ELISA. HBcrAg serum levels of F2, F3 and F4stage patients were significantly higher than those of nonsignificant liver fibrosis patients (METAVIR F0-F1), but there were no significant differences among F2, F3 and F4stage patients. Serum HBcrAg (OR, 2.18; 95% confidence interval [CI], 1.51-3.16), albumin (ALB) (OR, 0.60; 95% CI, 0.41-0.87), prothrombin activity (PTA) (OR, 0.58; 95% CI, 0.40-0.83) and platelet (PLT) counts (OR, 0.38; 95% CI, 0.25-0.57) were associated with significant liver fibrosis (METAVIR F2-F4). The serum HBcrAg value enabled the correct identification of patients with significant fibrosis, with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.75-0.88). The APRI, FIB-4 index and ALBI score can identify significant liver fibrosis with an area under the ROC curve of 0.74 (95% CI, 0.66-0.81), 0.73 (95% CI, 0.65-0.80) and 0.63 (95% CI, 0.55-0.72), respectively. Compared with these three indexes, the accuracy rate of diagnosis of significant fibrosis based on HBcrAg was higher than that of the FIB-4 index (p=0.0479) and ALBI score (p=0.0030). HBcrAg, ALB, PTA serum levels and PLT counts were associated with significant liver fibrosis in treatment-naive chronic HBV infection patients. HBcrAg serum levels enabled the correct identification of patients with significant fibrosis (METAVIR F2-F4), and HBcrAg was moreeffective than the FIB-4 index and ALBI score.

Efficacy of ursodeoxycholic acid for primary biliary cholangitis: Experience from a tertiary care centre in Saudi Arabia.

Primary biliary cholangitis (PBC) is a progressive autoimmune cholestatic liver disease that primarily affects females more than males and may lead to end-stage liver disease. We studied baseline characteristics, and the biochemical and clinical response to ursodeoxycholic acid (UDCA), a first-line treatment option for patients with PBC, in a cohort of patients diagnosed with PBC from Saudi Arabia. A total of 30 patients meeting the diagnostic criteria of PBC who were being followed in the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, between January 1, 2008, and December 31, 2017, were enrolled in the study. The patients with autoimmune hepatitis, primary sclerosing cholangitis, and overlap syndromes were excluded. The baseline characteristics of the patients were recorded. The response to UDCA treatment was assessed according to the Barcelona, Paris I, Paris II, and Toronto criteria, and clinical outcomes, and biochemical changes were ascertained. The mean age was 46 years ± 11.7 with a female gender predominance of 93% (n = 28). Pruritus was the predominant symptom reported by 90% (n = 27) of the patients. A total of 23 (77.7%) patients underwent liver biopsy and all of them showed histological features suggestive of PBC. Cirrhosis was documented in 30% (n = 9) of the patients at baseline. Overall, 86.7% (n = 26) of the patients were positive for antimitochondrial antibodies. The biochemical response rates to UDCA based on Paris I, Paris II, Barcelona, and Toronto criteria were 73.3, 40, 56.7, and 53.3%, respectively. Over 10 years, 30 patients with PBC were diagnosed at a large referral center in Saudi Arabia. The response to UDCA treatment was inadequate.

Assessment of liver fibrosis by transient elastography and multi-parameters model in young children with chronic hepatitis B virus infection

ObjectiveThis study aimed to compare the diagnostic value of the single or combined applications of transient elastography (TE) and multivariate indicators with biopsy for the detection of liver fibrosis in children caused by chronic hepatitis B (CHB).MethodsThis study included 148 CHB children treated at Hunan Children’s Hospital from January 1st 2015 to December 31st 2018, aged from 0.83 to 14.58 years old. All patients underwent liver biopsy (LB), of which 43 patients underwent TE. Multiple clinical data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Platelet (PLT), and HBV-deoxyribonucleic acid (HBV DNA) of all patients were collected. The diagnostic values for CHB of TE and its combinations with these indicators were measured. The patients were classified in two ways: no hepatic fibrosis group (F0) versus fibrosis group (F ≥ 1), and no significant hepatic fibrosis group (F < 2) versus significant hepatic fibrosis group (F ≥ 2). The statistical assessment was performed between groups within each classification to compare the diagnostic value of different parameters.ResultsThe operating characteristic area under curve (AUC) of liver fibrosis diagnosed by liver stiffness measurement (LSM) which obtained by TE, AST-to-PLT ratio index (APRI), and fibrosis-4 index (FIB-4) were 0.740, 0.701, and 0.651, while the corresponding cut-off values were 5.9 kPa, 0.50, and 0.10, respectively. The AUC of significant liver fibrosis diagnosed by LSM, APRI and FIB-4 were 0.849, 0.701, and 0.509, while the corresponding cut-off values were 8.4 kPa, 0.76, and 0.08, respectively. While with the combinations of LSM and APRI, LSM and FIB-4, LSM and APRI and FIB-4, APRI and FIB-4, the AUC of significant liver fibrosis were 0.866, 0.855, 0.869, and 0.684, respectively. The AUC of significant liver fibrosis diagnosed by the LSM was significantly higher than APRI and FIB-4.ConclusionsThe diagnostic value of transient elastography was better than that of APRI and FIB-4 for CHB children with significant liver fibrosis. In addition, TE also has relatively high application values on the diagnosis of patients with different degrees of liver fibrosis caused by CHB.

Graves\u2019 disease overlapping with chronic hepatitis B and methimazole-induced liver injury and autoimmune hepatitis: a case report

BackgroundLiver injury related to Graves’ Disease (GD) includes hepatotoxicity of thyroid hormone excess, drug-induced liver injury, and changes resulting from concomitant liver disease. Methimazole (MMI) has been shown to induce several patterns of liver injury. However, the diagnosis and treatment of autoimmune hepatitis (AIH) overlapping with either GD or chronic hepatitis B are challenging.Case presentationA 35-year-old man from China presented with a two-year history of GD and a 10-day history of progressive jaundice. He had taken MMI for two months and discontinuing treatment due to liver toxicity 1 year ago and for another 6 days 20 days prior to hospitalization. The patient was diagnosed with GD overlapping with chronic hepatitis B and MMI-induced liver injury with early stage of acute-on-chronic liver failure on admission. However, the elevated aminotransferase and bilirubin levels could not be controlled after correction of liver failure and effective control of HBV replication and hyperthyroidism by daily oral entecavir and one-time oral administration of 131-iodine. The patient underwent liver biopsy on the 43rd day of hospitalization, showing HBsAg expression on the membrane of hepatocytes and typical histopathological characteristics of AIH. He was finally diagnosed with GD overlapping with chronic hepatitis B and MMI-induced liver injury and AIH. The elevated aminotransferase and bilirubin completely returned to normal by 3-month glucocorticoid therapy and continuous entecavir treatment and there was no recurrence during a 6-month follow-up, suggesting that AIH in this patient is different from classical AIH or GD-associated AIH.ConclusionsGD together with AIH is a complex and difficult subject. It needs to be clarified whether MMI or HBV can act as a trigger for AIH in this patient.

Pain levels of patients undergoing ultrasound guided biopsies and associated factors: a cross-sectional study

Aim: Patients may experience pain in minimally invasive biopsy procedures. It is important to evaluate the degree of pain and to know the factors that determine the level of pain felt by patients for adequate pain management. The aim of this study is to determine the pain levels felt by patients and socio-demographic and clinical factors associated with higher pain levels in breast and liver biopsy procedures.&#x0D; Material and Method: In this cross-sectional observational study, patients who will undergo ultrasound-guided breast and liver biopsy procedures in the study center were invited to the study. The pain level was measured with the Visual Analogue Scale (VAS). Pain measurements above 45mm were classified as moderate-to-high pain levels. The State-Trait Anxiety Scale was used to measure the anxiety levels of the patients and the radiologist. Sociodemographical (sex, age, education level, job, income) and clinical factors (biopsy site, duration, bosy mass index, anxiety level of the patient and the radiologist) that may be associated with the pain levels of the patients were analyzed.&#x0D; Results: The sample consisted of 76 patients, 62 were female (81.6%). The procedures consisted of 43 breast biopsies (56.6%), 33 liver biopsies (43.4%). The median pain level measurement determined by the VAS is 20.0mm (IQR: 9.3- 38.5). Most of the sample (59.2%) stated that they felt mild pain. It was found that patients with higher anxiety levels and patients underwent liver biopsy had statistically significantly higher moderate-to-high pain levels than patients with lower anxiety (OR: 3.683 95% CI: 1.159- 11.705, p=0.220), patients who underwent breast biopsies (OR: 3.521, 95% CI: 1.153- 10.752, p=0.023). A positive correlation was found between the level of pain and the level of anxiety (r=0.267, p=0.020).&#x0D; Conclusion: This study demonstrated that most ultrasound-guided biopsy procedures were performed with mild or no pain although higher patient anxiety levels were associated with higher pain levels during the procedures. Patients undergoing liver biopsy procedures had higher pain levels than breast biopsy procedures.

Hepatic amyloidosis: a prevalence study and clinical characterization of a rare and severe disease.

Amyloidosis is a systemic disease characterized by extracellular deposition of amyloid protein, most commonly in the heart and kidney. Hepatic amyloidosis is a rare form of presentation that ranges from mild hepatomegaly and altered liver biochemical tests to acute liver failure. The aims of this study were to evaluate the prevalence of amyloidosis in patients undergoing liver biopsy and describe its main clinical characteristics and prognostic impact. A retrospective analysis of all patients with a histological diagnosis of hepatic amyloidosis between January 2010 and December 2019 was performed. A total of 7 patients were identified from a total of 1773 liver biopsy procedures (0.4%), with a female predominance (6/7) and median age of diagnosis of 62 years. The most common clinical manifestations included hepatomegaly (4/7), jaundice (2/7) and peripheral edema (2/7), whereas 3/7 patients were asymptomatic. Every patient presented abnormalities in liver biochemical tests, more commonly cholestasis (6/7), but also cytolysis (4/7) or hyperbilirubinemia (2/7). Abnormal imaging findings included hepatomegaly, steatosis or parenchymal heterogeneity. In most patients (5/7), other organs were involved, most commonly with nephrotic syndrome (3/7) and infiltrative cardiomyopathy (3/7). The most common type was AA amyloidosis (3/7) followed by AL amyloidosis (2/7). The 1-year mortality rate was 43% and the median survival was 24 months. We report a low prevalence (0.4%) of amyloidosis among patients undergoing liver biopsy. Although rare, hepatic amyloidosis is associated with a dismal prognosis and a high index of suspicion is crucial to achieve an early diagnosis. .

Determination of "indeterminate score" measurements in lean nonalcoholic fatty liver disease patients from western Saudi Arabia.

BACKGROUNDNoninvasive measures to estimate liver fibrosis in lieu of biopsy in nonalcoholic liver disease (NAFLD) can broadly differentiate high vs low degrees of condition extent. However, an “indeterminate score” necessitates further clinical investigation and biopsy becomes essential, highlighting the need for identification of other noninvasive factors with accuracy for this midlevel extent and its prognosis. Lean NAFLD cases are of particular interest regarding this issue, as they present as otherwise healthy, and will benefit greatly from the less invasive assessment.AIMTo estimate the agreement of two noninvasive assessment tools in lean NAFLD patients, and assess factors related to indeterminate scores.METHODSUltrasound-diagnosed NAFLD patients, without sign of other chronic liver disease (n = 1262), were enrolled from a tertiary private medical centre between 2016-2019. After grouping by body mass index (obese, overweight, and lean), each participant underwent FibroScan. NAFLD fibrosis score (NFS) was used for subclassification (lower, higher, and indeterminate). No patient underwent liver biopsy. The kappa statistic was used to assess inter-rater agreement between the three groups on liver fibrosis degree assessed via FibroScan and NFS. Indeterminate score among the three groups was assessed to identify factors that predict its determination. RESULTSThe NAFLD study cohort was composed of lean (159/1262, 12.6%), overweight (365/1262, 29%) and obese (737/1262, 58.4%) individuals. The lean patients were significantly younger (49.95 ± 15.3 years, P < 0.05), with higher serum high density lipoprotein (52.56 ± 16.27 mg/dL, P < 0.001) and lower prevalences of type 2 diabetes mellitus, hypertension and hyperlipidaemia. All groups showed a predominance of lower fibrosis degree. The lean NAFLD patients showed a significantly lower NFS (P < 0.001). Degree of agreement between FibroScan and NFS was fair between the lean and obese NAFLD categories, and moderate in the overweight category. NFS was predictive of indeterminate score. Age was a factor among all the body mass index (BMI) categories; other associated factors, but with less strength, were serum alanine aminotransferase in the overweight category and BMI in the obese category.CONCLUSIONLean NAFLD patients showed lower degree and prevalence of liver fibrosis by NFS; however, follow-up biopsy is still needed.

Community Socioeconomic Deprivation Predicts Nonalcoholic Steatohepatitis.

In order to determine the relationship between socioeconomic deprivation and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), we retrospectively reviewed the electronic medical records of 1,430 patients in a large tertiary health care network in New York. These patients underwent liver biopsy over a 10‐year period and were included in our study if they had evidence of NAFLD/NASH on liver biopsy. Zip codes were used to obtain data necessary to derive the social deprivation index (SDI) from the US Bureau of the Census. The high‐SDI group was compared to the low‐SDI group. Univariate and multivariate logistic regressions were performed to assess association between socioeconomic factors and NAFLD parameters, including presence of NASH (NAFLD activity score >4), moderate to severe steatosis (>33%), and significant fibrosis (S2‐S4). We included 614 patients with NAFLD/NASH; the median SDI was 31.5. Hemoglobin A1c values were higher in the high‐SDI group compared to the low‐SDI group (6.46 vs. 6.12, P = 0.02). Socioeconomic factors, such as private versus public health care, percentage being foreign born, percentage without a car, percentage with higher needs (<5 years old and >65 years old), and percentage currently living in renter‐occupied and crowded housing units, showed statistically significant associations in predicting NASH. After adjusting for patient age, sex, race, body mass index, and diabetes, we saw a significant association between four or more socioeconomic parameters in predicting NASH (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.099‐2.856; P = 0.0190) and six or more socioeconomic parameters in predicting severe steatosis (OR, 1.498; 95% CI, 1.031‐2.176; P = 0.0338) but no significant correlation between the number of socioeconomic parameters and significant fibrosis. Conclusion: Greater number of socioeconomic determinants (four or more) are associated with greater severity of NASH. Awareness of NAFLD/NASH needs to be raised in communities with high socioeconomic deprivation.

S2817 Glycopenic Hepatopathy in a Patient With Recurrent Diabetic Ketoacidosis: A Rare Complication of Poorly Controlled Type 1 Diabetes Mellitus

Introduction: Glycogenic hepatopathy (GH) is a rare condition predominately seen in patients with poorly controlled type 1 diabetes mellitus. This condition develops due to excessive accumulation of glycogen in the hepatocytes, leading to significant hepatomegaly and transient liver dysfunction with elevated liver enzymes. Case Description/Methods: A 24-year-old female with a history of poorly controlled type 1 diabetes mellitus complicated by multiple admissions for diabetic ketoacidosis (DKA) presented with acute onset abdominal pain, nausea and vomiting. Physical exam was significant for tender hepatomegaly. Admission laboratory results were significant for serum glucose 189 mg/dL, bicarbonate 5 mmol/L, anion gap 35 mmol/L, beta-hydroxybutyrate 6.5 mmol/L, and HbA1c 11.4%. Admission hepatic panel was significant for alanine aminotransferase 31 U/L, aspartate aminotransferase 56 U/L, alkaline phosphatase 138 U/L with normal bilirubin and prothrombin time. Patient was treated with insulin and intravenous fluids with resolution of her DKA. However, her clinical course was complicated by persistent abdominal pain with an acute rise in liver enzymes (alanine aminotransferase 216 U/L, aspartate aminotransferase 249 U/L, alkaline phosphatase 116 U/L with normal bilirubin and prothrombin time). Triglyceride level was elevated at 214mg/dL. Abdominal computed tomography was notable for hepatomegaly with liver size of 24 cm. Workup for hepatitis, HIV, COVID-19, autoimmune hepatitis, hemochromatosis, and Wilson's disease were negative. Patient underwent liver biopsy that demonstrated diffuse hepatocyte cytoplasmic clearing, consistent with GH. The patient was medically managed with strict glycemic control, diabetic diet and endocrinology input throughout admission. One week after hospital discharge, the patient remained asymptomatic and liver function tests returned to normal limits. Discussion: GH is a rare condition that should be considered in patients with poorly controlled diabetes mellitus who present with hepatomegaly and acute liver injury. While GH presents similarly to NAFLD, it can only be differentiated and definitely diagnosed by liver biopsy. This condition should not be overlooked as it is a favorable diagnosis with a good prognosis compared to other liver disease associated with diabetes mellitus. Further studies are needed to better understand the characteristics of this disease, and future development of non-invasive, rapid diagnostic testing could help avoid extensive and costly workups. (Figure Presented).

S1120 When Your Lab Didn’t Read the Guidelines: The Ability of Physicians in a Teaching Hospital Clinic to Identify Abnormal Alanine Aminotransferase (ALT) Values

Introduction: ACG guidelines define normal ALT as 29 to 33 for males and 19 to 25 for females. An elevated ALT, even if borderline, warrants consideration as to the cause, and monitoring for worsening. However, different laboratories use different reference values for normal, and many report ALTs greater than 25 or 33 as normal. Our hospital’s lab reports ALT 6-55 as normal. In this study, we aimed to assess physicians’ identification of abnormal ALT values, particularly in instances when the lab did not identify it as abnormal (by bolding). Methods: We reviewed the charts of 4965 patients seen in Internal Medicine (IM) and GI clinics to identify patients with elevated ALTs. Only the first instance of elevated ALT was included for each patient. We excluded patient who had a history of liver disease. We identified the patients who had ALTs that were abnormal but not marked as such by the laboratory. For each patient, we reviewed the clinic notes to find any comment or plan for work-up. Results: Results are summarized in the chart and table. 1018 patients with elevated ALT and no history of liver disease were identified and included. Elevated ALT was identified by the physician in 29.1% of patients. Of elevated ALT values that were less than 55, only 31/491 were identified. Of these 31 patients, 11 were not seen again and 5 had no additional testing. One patient underwent liver biopsy. The rest had an ultrasound and serologic testing. After work-up, two patients were presumed to have alcoholic liver disease, 5 NAFLD, one was diagnosed with choledocholithiasis, and 3 were diagnosed with DILI. Furthermore, there was a significant difference in the identification of abnormal ALTs between 50-55 (not bolded) and ALTs between 56-64 (bolded): ALT of 50-55 was identified as abnormal in 16.4% of visits, while ALT of 56-64 in 39.7% (P-value .005). Of note, GI physicians were significantly more likely to identify elevated ALT values than IM physicians (see table). Conclusion: Physicians were more likely to identify an abnormal ALT if it was bolded. In both clinics, non-bolded ALTs were largely ignored. Amongst the patients whose non-bolded elevated ALT were identified, most received additional testing and were found or presumed to have modifiable etiologies. This study demonstrates the need for physicians to better familiarize themselves with normal ranges of liver tests, and consider the need for further evaluation or monitoring when an ALT value is abnormal even if their laboratory does not identify it as such.Table 1Figure 1.: Identification of Elevated ALT as Abnormal. Blue bar shows GI clinic; Orange bar shows IM clinic; Gray bar shows Total

Elevation of microRNA-214 is associated with progression of liver fibrosis in patients with biliary atresia.

MicroRNAs (miRNAs) play an important role in regulating fibrogenesis in the liver. The current study examined the ability of microRNA-214 (miR-214) level in liver and serum samples obtained from patients with BA to predict progressive liver fibrosis in patients with biliary atresia (BA). We examined miR-214 level in relation to conventional markers of liver fibrosis, with liver and serum samples from BA patients. Fifty-two patients with BA who underwent Kasai portoenterostomy and four control patients underwent liver biopsy. In 28 patients with BA, blood samples were collected to analyze circulating serum miR-214. MiR-214 levels in liver tissue were significantly upregulated in patients with BA who had severe liver fibrosis (F3-4) compared to those with none to mild fibrosis (F0-2), whereas suppressors-of-fused homolog (Sufu) mRNA levels were significantly suppressed in F3-4. Serum miR-214 levels were significantly higher in patients with F3-4 compared with F0-2. Area under the curve analysis showed that the serum miR-214 cut-off level for predicting F3-4 was 0.805 (p = 0.0046). Hepatic overexpression of miR-214 is associated with progression of liver fibrosis in patients with BA, and the circulating miR-214 level may serve as a non-invasive predictor of liver fibrosis.

O-24 A CASE SERIES OF CHLOROQUINE MONOTHERAPY TO INDUCE BIOCHEMICAL REMISSION IN PATIENTS WITH RELAPSED AUTOIMMUNE HEPATITIS

Azathioprine (AZA) and prednisone (PD) are the standard treatment (ST) for the onset or relapse of autoimmune hepatitis (AIH). Antimalarials were effective for maintenance of remission of AIH after immunosuppression withdrawal. Our aim is to describe a series of patients who relapsed after antimalarial withdrawal and achieved biochemical remission after reintroduction of chloroquine in monotherapy. Eight patients received chloroquine diphosphate (DCQ) 250mg/d or hydroxichloroquine (HCQ) 400-800mg/d in monotherapy for biochemical remission after relapse. The schedule is described below: histological remission (HR) with ST → ST withdrawal and antimalarial use for maintenance of remission for 1-3y → antimalarial withdrawal → relapse of AIH → reintroduction of antimalarial instead of ST, at the request of patient due to corticosteroids side effects (SE). Four out of 8 patients underwent liver biopsy to evaluate HR after at least 18mo of biochemical remission. Mean age at diagnosis of AIH of 36.2 ± 20.4y; 6 type-1, 2 anti-SLA/LP (5 reactive in 7 tested); 3 with cirrhosis at diagnosis. Mean doses of AZA/PD at HR were, respectively, 84.4 ± 18.6 and 9.4 ± 2.2mg/d. Mean interval between antimalarial withdrawal and relapse was 20.5 ± 34.1mo. Mean ALT at relapse was 139.7 ± 54.2 U/L. Three patients received DCQ and 5 HCQ. During HCQ intake 1 patient needed further adjustment of drug to 800 mg/d for 15 days due to worsening of ALT from 130 to 246 U/L, with subsequent reduction to the initial dose. Seven patients achieved biochemical remission, in a mean time of 14.2 ± 19.9mo; 3/4 had histological remission. The drug was well tolerated and there were no serious SE. CQ monotherapy was safe and effective for induction of remission in this subgroup of AIH. This finding raises arguments to include this drug as an option for treatment of AIH, not necessarily in monotherapy.

P-31 NORMAL TRANSAMINASES IN OBESE PATIENTS WITH METABOLIC ASSOCIATED STEATOHEPATITIS

Metabolic associated fatty liver disease (MAFLD) and metabolic associated steatohepatitis (MASH) are the most frequent causes of chronic liver disease. Measurement of transaminases may not correlate with the severity of histopathological changes. We aimed to identify the frequency of normal and elevated transaminases in obese patients with MASH, as well as their clinical, biochemical and histological characteristics. A retrospective cross-sectional study was conducted in the bariatric surgery service of a private clinic. Obese patients older than 18 years with a body mass index (BMI) >30Kg/m 2 and 2 co-morbidities undergoing a gastric sleeve surgery were included. Measurement of biochemical routine laboratory exams was performed. Insulin resistance was calculated using the homeostasis evaluation model (HOMA-IR). All patients underwent liver biopsies prior to surgery and the diagnosis of MASH was based on the Brunt criteria. 159 obese patients with MASH were included, of which 47.2% had normal transaminases and 52.8% elevated transaminases. Factors associated with alteration in transaminases were: being male OR=4.02 (95% CI: 2.03-7.96; p<0.01), diagnosis of type 2 diabetes mellitus OR=4.86 (95% CI: 1.97-11.95; p<0.01) and levels of GGT >50 IU/L OR=7.50 (95% CI: 3.40-16.56; p<0.01). The values of HOMA-IR and GGT were significantly higher in the group of high transaminases (p<0.01). Differences in the degree of fibrosis were not associated with transaminases levels. In conclusion we found that 47.2% of obese patients with MASH had normal transaminases. The degree of fibrosis was not associated with transaminases levels.

Pentraxin-3: A Novel Marker for Indicating Liver Fibrosis in Chronic Hepatitis B Patients?

PTX-3 is an important marker that plays a role in suppressing inflammation and tissue repair. The aim of this study is to investigate the diagnostic and prognostic characteristics of PTX-3 in CHB patients and the relationship between PTX-3 levels and fibrosis. A total of 52 CHB patients and 40 healthy subjects were included in the study. All of the CHB patients underwent liver biopsy and were then scored using a Ishak histologic scoring system. Blood samples were collected to evaluate the PTX-3 levels. Of the subjects who participated in the study, 53% were female. PTX-3 levels were determined as 5.63ng/mL in the control group, and as 0.88ng/mL in the CHB patient group. PTX-3 levels were found to be 1.19ng/mL in stage 1, 0.89ng/mL in stage 2, 0.68ng/mL in stage 3 and 0.55ng/mL in stage 4. Of the CHB patients, 44.2% had significant fibrosis, while 55.7% were identified as not having significant fibrosis. PTX-3 values were 0.64 and 1.0ng/mL in patients with and without significant fibrosis, respectively. The cut-off value for PTX-3 in predicting the absence of significant fibrosis was estimated as 0.9ng/mL. CHB patients were found to have lower serum PTX-3 levels compared to the control group, and these levels decreased even further as the fibrosis stage progressed in these patients. In addition, the significant decrease in PTX-3 levels in patients with stage 1 fibrosis compared to the control group shows that PTX-3 can be used as a non-invasive marker for the early detection of fibrosis (p<0.001).

Usefulness of New Shear Wave Elastography Technique forNoninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study.

To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis. This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated. Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05). STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.

Non-invasive diagnostic imaging tests largely underdiagnose cardiac cirrhosis in patients undergoing advanced therapy evaluation: How can we identify the high-risk patient?

Patients with liver cirrhosis are generally considered ineligible for isolated cardiac transplantation or left ventricular assist device (LVAD) implantation. The aim of this retrospective study is to explore the diagnostic value of abdominal ultrasound, computed tomography scan (CT scan) and liver-spleen scintigraphy to detect the presence of cirrhosis in patients with advanced heart failure. Among 567 consecutive patients who underwent pre-transplantation or LVAD evaluation, 54 had a liver biopsy to rule out cardiac cirrhosis; we compared the biopsy results with the imaging investigations. In about 26% (n=14) of patients undergoing liver biopsy, histopathological evaluation identified cirrhosis. The respective sensitivity of abdominal ultrasound, CT scan and liver-spleen scintigraphy to detect cirrhosis was 57% [29-82], 50% [16-84], and 25% [3-65]. The specificity was 80% [64-91], 89% [72-98], and 44% [20-70], respectively. Ultrasonography has the best-combined sensitivity and specificity for the diagnosis of cirrhosis. However, more than a third of patients with cirrhosis will go undiagnosed by conventional imaging. As liver biopsy is associated with a low rate of complication, it should be considered in patients with a high-risk of cirrhosis or with evidence of portal hypertension to assess their eligibility for heart transplantation or LVAD implantation.

Liver and serum adiponectin levels in non‐alcoholic fatty liver disease

Adiponectin is an adipokine that has anti-steatotic, anti-inflammatory and anti-fibrotic effects. The impact of these different activities impact on the development and progression of non-alcoholic fatty liver disease (NAFLD) is not well understood. The aim of this study was to evaluate both liver and serum adiponectin levels in patients with and without NAFLD and determine any clinical correlations. Liver tissue and serum samples were collected from patients undergoing liver biopsy between April 2014 and July 2020, and categorized based on histopathological diagnosis into hepatic steatosis (HS), non-alcoholic steatohepatitis (NASH), and hepatitis control (HC). A Luminex xMAP assay was performed on both liver and serum samples to measure adiponectin levels. Statistical analysis compared liver adiponectin (LA) and serum adiponectin (SA) levels between groups. A total of 48 participants were included in the analysis. The mean LA level was lowest in the HS group, followed by the NASH group and the HC group (P = 0.036). The mean SA level was 3.61 μg/mL for the NAFLD group and was significantly lower than that in the HC (7.51 μg/mL; P = 0.001). Adiponectin levels are lower in NAFLD compared to HC in both serum and liver tissue. LA levels in patients with HS were significantly lower than in both the NASH and HC groups, suggesting that adiponectin is related to inflammation in the liver and probably reflects its role in the pathogenesis of NAFLD.

The Utility of Liver Biopsy in the Evaluation of Liver Disease and Abnormal Liver Function Tests

We aimed to assess the value of liver biopsy in the evaluation of abnormal liver tests. We analyzed consecutive liver biopsy specimens performed for evaluation of unexplained abnormal liver tests from 2014 to 2018. Diagnoses were categorized histologically and clinically. We determined whether histologic examination led to a specific diagnosis and whether prebiopsy laboratory variables predicted the underlying etiology. Among the 383 liver biopsy specimens included, chronic hepatitis was the most common histologic (25%) and clinical (17%) diagnosis. Liver biopsy led to a clinical diagnosis in 87% of patients. The most likely clinical diagnoses were autoimmune hepatitis, nonalcoholic fatty liver disease, and drug-induced liver injury (38, 33, and 32 patients, respectively). Using sensitivity, specificity, and positive and negative predictive values, we found that liver tests were not predictive of a specific diagnosis. In patients with no history of liver disease or clinical features of portal hypertension, biopsy specimens revealed histologic cirrhosis in 5% of patients. Histopathologic diagnoses were made in 85% of patients undergoing liver biopsy for investigation of unexplained liver tests, leading to a clinical diagnosis in 87% of patients. However, neither liver tests themselves nor their patterns were useful in predicting histologic or clinical diagnoses.

A Rare Case of Acute Liver Failure Secondary to Diffuse Hepatic Infiltration of Small Cell Neuroendocrine Carcinoma.

BackgroundMalignant liver infiltration is an uncommon cause of acute liver failure (ALF) and has rarely been reported.Case PresentationWe present a patient with progressive jaundice and dissociation of bilirubin and aminotransferases, who had no history of relevant liver diseases or tumor except the use of Chinese traditional drugs for a cold. An abdominal computed tomography (CT) scan showed ascites without hepatic focal lesions. Laboratory studies revealed no evidence of hepatitis or underlying autoimmune disorders. Following 8 days of conservative management ALF rapidly worsened. Contrast-enhanced CT revealed diffuse regenerative nodules in the liver. The patient underwent liver biopsy, which demonstrated that the liver was infiltrated by pulmonary neuroendocrine tumor classified as small cell lung cancer. The patient died 13 days after diagnosis.Discussion and ConclusionsThis case represents a rare cause of ALF induced by pulmonary neuroendocrine tumor of small cell type and illustrates the importance of prompt biopsy in an unknown cause of ALF.