Family History Of Liver Disease Research Articles

A286 MYO5B MUTATIONS AS A CAUSE OF CHOLESTASIS IN A CHILD WITHOUT MICROVILLOUS INCLUSION DISEASE

Abstract Background Biallelic Myosin Vb (MYO5B) mutations are identified in the majority of patients with microvillus inclusion disease (MVID) that requires life-long parenteral nutrition and eventually cholestatic liver disease. Biallelic MYO5B mutations have also been reported in a few children with predominant early-onset cholestatic liver disease. Aims To report on a patient with MYO5B mutations and progressive familial intrahepatic cholestasis PFIC-like phenotype and normal serum GGT without intestinal disease. Methods We describe a 2-year and 8-month-old girl, who is the first child of healthy non- consanguineous parents from the Phillipines with no family history of liver disease. She presented at the age of 10 months for evaluation of mild jaundice, which was noticed at the age of 6 months. Other symptoms included pruritus, slowly weight gain, intermittent pale stools and dark urine. Laboratory investigations revealed AST 99, ALT 87, GGT 27, conjugated bilirubin 13 and INR 0.8. Fasting abdominal ultrasound was normal apart from a possibly hypoplastic gallbladder and mild splenomegaly. Additional investigations revealed normal thyroid-stimulating hormone, cortisol, galactosemia screening and sweat chloride, but bile acids were elevated 391.6 umol/L. A liver biopsy was performed and a cholestasis genetic panel sent. The patient was started on ursodiol, hydroxyzine, rifampicin and vitamin D. Results Liver biopsy revealed moderate hepato-canalicular cholestasis, bile duct injury without prominent ductopenia, small caliber bile ducts with no features of obstructive cholangiopathy, mild periportal and pericentral fibrosis stage 1-2/ 4. Electron microscopy demonstrated cytoplasmic and canalicular bile accumulation. The bile canaliculi were variably distended by coarse granular bile. Immunohistochemical staining for BSEP and MDR3, showed canalicular staining in zones 1 and absence of staining in zones 2 and 3. Genetic analysis revealed one pathogenic variant and one variant of uncertain significance in MYO5B. No mutations in ABCB11 or ATP8B1 genes were identified. On follow-up, the jaundice improved, pruritus was managed with the medications described above. Her growth has improved and she is growing on the 25th centiles. She has not developed any gastrointestinal symptoms. Conclusions We present a patient with MYO5B mutations who presented with normal GGT cholestasis and a liver biopsy consistent with PFIC, without any evidence of intestinal disease. Because MYO5B mutations disrupt the intracellular trafficking of brush border proteins in the intestine, it has been assumed that it similarly disrupts the trafficking of the canalicular bile acid transporting and bilirubin transporting proteins in the liver. This case highlights the broad phenotype associated with MYO5B variants. Funding Agencies None

Advancing diagnosis and management of liver disease in adults through exome sequencing

Whole-exome sequencing (WES) is an effective tool for diagnosis in patients who remain undiagnosed despite a comprehensive clinical work-up. While WES is being used increasingly in pediatrics and oncology, it remains underutilized in non-oncological adult medicine, including in patients with liver disease, in part based on the faulty premise that adults are unlikely to harbor rare genetic variants with large effect size. Here, we aim to assess the burden of rare genetic variants underlying liver disease in adults at two major tertiary referral academic medical centers. WES analysis paired with comprehensive clinical evaluation was performed in fifty-two adult patients with liver disease of unknown etiology evaluated at two US tertiary academic health care centers. Exome analysis uncovered a definitive or presumed diagnosis in 33% of patients (17/52) providing insight into their disease pathogenesis, with most of these patients (12/17) not having a known family history of liver disease. Our data shows that over two-thirds of undiagnosed liver disease patients attaining a genetic diagnosis were being evaluated for cholestasis or hepatic steatosis of unknown etiology. This study reveals an underappreciated incidence and spectrum of genetic diseases presenting in adulthood and underscores the clinical value of incorporating exome sequencing in the evaluation and management of adults with liver disease of unknown etiology. S.V. is supported by the NIH/NIDDK (K08 DK113109 and R01 DK131033-01A1) and the Doris Duke Charitable Foundation Grant #2019081. This work was supported in part by NIH-funded Yale Liver Center, P30 DK34989.

Contribution of Aflatoxin B1 Exposure to Liver Cirrhosis in Eastern Ethiopia: A Case-Control Study.

Liver cirrhosis is a global health problem due to a large number of disability-associated life years and mortality. However, evidence is scarce on its causes in Eastern-Ethiopia, a place where there is a high prevalence of liver cirrhosis of unknown etiology. This study attempted to identify the risk factors related to liver cirrhosis in the area. A case-control study was conducted at a tertiary care hospital from January 2020 to July 2021. Following diagnoses using an ultrasound-based cirrhosis scale, a total of 127 cases were identified and compared with 253 control patients. A structured questionnaire and data abstraction form were used to collect demographic, lifestyle, and clinical information. A blood sample was also taken from each participant for clinical chemistry, hepatitis B virus (HBV), and hepatitis C virus tests as well as for an aflatoxin B1 (AFB1) albumin adduct (AF-alb) assay. Binary logistic regression analysis was used to determine predictors of liver cirrhosis. AF-alb levels were detected in 75% of the cases and 64% of the controls, with a median (IQR) level of 11 pg/mg (5.5-25) and 7.0 pg/mg (4.3-20.5), respectively (p<0.05). Moreover, the number of subjects with high AF-alb levels (≥8.6 pg/mg) was greater in cases (45%, p<0.05)) than controls (28%). Age ≥55 years (adjusted odds ratio (AOR)=0.4; 95% CI: 0.2, 0.8), being a farmer (AOR= 3.0; 95% CI: 1.5, 6.0), family history of liver disease (AOR= 2.9; 95% CI: 1.1, 7.9), HBV seropositivity (AOR=4.0; 95% CI: 1.9, 8.8), and exposure to high levels of AF-alb (AOR=2.0; 95% CI: 1.1, 3.7) were significantly associated with liver cirrhosis. This study found a strong link between AFB1 exposure and liver cirrhosis. Mitigation of aflatoxin exposure and a better understanding of additional environmental risk factors like pesticides may be necessary to reduce the disease burden in Ethiopia.

A261 SEVERE ACUTE LIVER INJURY SECONDARY TO WILSON’S DISEASE: A CASE REPORT AND REVIEW OF THE LITERATURE

Abstract Background Wilson’s disease is autosomal recessive and rare (prevalence 1/30000-1/50000) caused by mutations in the ATP7B gene involved in copper excretion. Copper deposition drives hepatic injury, along with neuropsychiatric-ophthalmologic, and hematologic symptoms. Leipzig criteria greater than 4 establishes the diagnosis. Purpose We report a case of severe liver injury secondary to probable Wilson’s disease. Method Literature review of diagnosis, management including emerging therapies was performed using PubMed. Result(s) A 29-year-old otherwise healthy male with no family history of liver disease presented with abdominal pain, jaundice, and severe acute liver injury (ALT 1534 U/L ALP 114 U/L bilirubin 113 umol/L) initially misdiagnosed as hepatitis A in community urgent care. He had worsening liver injury (ALT 1809 U/L bilirubin 411 umol/L), with normal INR and no encephalopathy over an additional 3 weeks and was admitted to our tertiary care centre for further work up. History did not reveal viral prodromes, herbals or natural remedies. CBD oil was the only potential exposure, though longstanding use of the same brand argued against this as a cause. Chronic liver disease workup was negative (viral hepatitides, SARS-CoV-2, alpha-1-antitrypsin, acetaminophen level, iron profile, and comprehensive Mitogen autoantibody panel). Patent vasculature on Doppler US. Liver biopsy showed diffuse lobular inflammation, hepatocyte necrosis, 30% parenchymal involvement, primarily lymphocytes with some eosinophils and plasma cells, and no viral inclusions suggesting acute hepatitis with drugs or viral hepatitis as etiologies. The 24-hour urine copper was elevated at 2.19 umol/d (&amp;lt;0.80). Biopsy copper dry weight 60mcg/g (N&amp;lt;50; &amp;gt;250 diagnostic). Normal ceruloplasmin 0.30g/L and serum copper 25.8 umol/L. MRI brain not suggestive of Wilson’s disease, no Kayser-Fleischer rings on Ophthalmology assessment, and no hemolysis. Given a Leipzig score of 3 suggesting possible Wilson’s disease he was started on penicillamine 1500mg daily. Five weeks later he had serologic (ALT 1061 U/L bilirubin 128 umol/L) improvement, yet elevated elastography at 22kPa IQR 5% likely due to inflammation. Given coverage issues, he was switched to compassionate trientine 500mg BID with further improvement (ALT 347 U/L bilirubin 26 umol/L). Sequencing for ATP7B gene mutations are pending (Blueprint Genetics). Conclusion(s) Wilson’s disease should be considered in those with hepatic or neuropsychiatric symptoms, transaminases in the 1000s or acute liver failure. Treatment is lifelong with typically good prognosis and is fatal if untreated. Treatment options include chelators D-penicillamine (first line, with side effects including proteinuria and worsened neurological symptoms) and trientine (fewer side effects). Zinc prevents copper absorption and can be used in asymptomatic patients. Transplant in acute liver failure and end-stage liver disease is guided by the King’s score. Several novel therapies including gene therapy are in development. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

The needle in the haystack: deciphering diagnostic data in a case of acute on chronic liver failure

The needle in the haystack: deciphering diagnostic data in a case of acute on chronic liver failure

An Unusual Manifestation of Elevated Liver Enzymes and Architecture

Question: A 68-year-old woman with a past medical history of cerebral vascular accident and chronic kidney disease underwent an outpatient anorectal examination under anesthesia for evaluation of a 6-month history of rectal bleeding and constipation. She was found to have a rectal mass involving the posterior vaginal wall. Biopsy specimens from the rectal and vaginal lesions showed invasive squamous cell carcinoma (SCC) with venous invasion (Figures A and B). The carcinoma was p16+ representing a high-risk human papilloma virus–induced SCC (Figure C). Computed tomography of the chest, abdomen, and pelvis showed the vaginal mass and a nodular liver suggestive of cirrhosis. With regard to the patient’s risk factors for liver disease, the patient had remote social alcohol consumption in her 20s without a history of intravenous drug use, family history of liver disease, autoimmune diseases, or hepatitis. In preparation for palliative chemotherapy, blood work was obtained, which was pertinent for white blood cell count of 8.8 103/μL, hemoglobin of 12.7 g/dL, platelets 257 103/μL, aspartate aminotransferase 127 U/L, alanine aminotransferase 65 U/L, alkaline phosphatase 1133 U/L, bilirubin 4.8 mg/dL, prothrombin time of 15.3 seconds, and international normalized ratio of 1.2. Serologic work-up was unremarkable for viral, autoimmune, or metabolic etiologies of liver disease, so magnetic resonance cholangiopancreatography was obtained (Figure D). Subsequently, the patient underwent transjugular hepatic hemodynamic pressure measurements with results as follows: right atrial pressure = 7 mm Hg, free hepatic vein pressure = 15 mm Hg, wedged hepatic vein pressure = 27 mm Hg, and corrected sinusoidal pressure = 12 mm Hg, followed by nontargeted liver biopsy (Figure E).

S3158 Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient’s improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion: DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient’s supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent liver transplantation. Our patient’s unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. Table 1. - The patient’s laboratory values, including total bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) improved after stopping Artemisinin/Bioperine Total bilirubin (mg/dL) ALP (U/L) AST (U/L) ALT (U/L) Initial labs with PCP 11 293 170 196 Repeat labs with PCP 5.6 143 75 98 3 weeks after stopping supplement 2.4 85 34 41

S3070 Macro AST: An Uncommon Yet Benign Entity

Introduction: An isolated increase in serum aspartate aminotransferase (AST) can be attributed to many conditions, including alcoholic liver disease, myocardial injury or skeletal muscle injury. Persistent elevations in AST without an obvious source can lead to diagnostic confusion. When evaluating such a patient, one must consider macro-enzyme aspartate aminotransferase (macro-AST). Macro-AST is an uncommon, yet benign condition in which a macro-enzyme is formed from self-polymerization of AST molecules or by the formation of a complex with other serum proteins such as immunoglobulins (Ig). These macro-enzymes circulate in the blood stream and can lead to an accumulation along with decreased clearance from the blood stream. Below, is an example of a woman without suggestive symptoms found to have persistently elevated AST. Case Description/Methods: The patient is a 60-year-old Hispanic female with hypothyroidism, hypertension who presented to the emergency room with complaints of lower back pain. Initial blood work revealed an AST of 404 U/L (normal 8-34 U/L) without other significant laboratory abnormalities. A computed tomography (CT) scan of the abdomen and pelvis with intravenous (IV) contrast showed lumbar spinal stenosis without other abnormalities. A right upper quadrant abdominal ultrasound with Doppler showed a normal appearing liver, biliary tree and patent vasculature. She denied any changes in her medications or use of supplements. She denied any history of liver disease, alcohol use or a family history of liver disease. Acetaminophen, ethanol and urine drug screens were negative. Testing for viral hepatitis, autoimmune hepatitis, ceruloplasmin, alpha-1-antitrypsin, ferritin, creatinine kinase, troponin I, Celiac disease and thyroid function tests were all unremarkable. Her AST level remained persistently elevated throughout hospitalization and after discharge. Given unremarkable workup and chronic AST elevation, macro-AST was the likely diagnosis. Discussion: Macro-AST is a benign cause of persistently elevated AST. Though its prevalence is not well known, some reports suggest that they can be seen across a wide age range and have no genetic basis as relatives of the patients have normal AST levels. Some cases have suggested a means of confirming the diagnosis via polyethylene glycol precipitation or electrophoresis. As these elevations can persist for over ten years, it is important for clinicians to be aware of this entity to avoid unnecessary procedures or testing.

S2919 Bile Duct Injury Due to Ketamine Use

Introduction: Ketamine is used routinely in the hospital for anesthesia, but is also used recreationally for its hallucinogenic and dissociative side effects. Chronic recreational use has been linked to bile duct damage and ulcerative cystitis. We report a case of ketamine induced sclerosing cholangiopathy. Case Description/Methods: A 42-year-old Cantonese woman with past medical history of bilateral hydronephrosis with stents leading to chronic kidney disease presented with abdominal pain associated with abnormal transaminases. Alkaline phosphatase was high at 1,017 IU/L with gamma glutamyl transferase of 2,310 IU/L with normal bilirubin. Abdominal imaging showed diffuse dilatation of the common bile duct. Viral serologies and anti-mitochondrial antibody were negative. She reported chronically elevated liver tests of unknown etiology. Social history was notable for prior alcohol abuse. She denied family history of liver diseases. Her pain resolved and plan was for outpatient follow-up, but she re-presented with sepsis with a rise in bilirubin to 2.9 mg/dL (Table 1). Given prior abnormal imaging, a magnetic resonance cholangiopancreatography was obtained, which showed increased intra- and extrahepatic bile duct dilation with irregular appearance of the central intrahepatic ducts with possible stricture. Differential diagnoses were recurrent pyogenic cholangitis, sclerosing cholangitis, and IgG4 disease. Her IgG level was high at 2,779 mg/dL with IgG4 elevated at 213 mg/dL. Liver biopsy showed chronic cholestatic liver injury consistent with sclerosing cholangitis (Image 1). IgG4 stain was negative. Upon further investigation, patient admitted to at least a decade of daily ketamine use, which was likely the culprit of both her kidney and liver diseases. Discussion: Due to her age, race, gender and rarity of ketamine induced cholangiopathy, she was not directly asked about ketamine use. Since the early 2000s, ketamine has emerged as the illicit drug of choice in Hong Kong and has seen increased use throughout Asia. The biliary damage from ketamine has been studied by a Chinese group that found 62% of the 257 chronic ketamine users had biliary tract anomalies. The greater the alkaline phosphatase, the higher the likelihood of finding biliary tract anomalies on imaging. Ketamine cessation has resulted in normalization of liver tests and imaging, however worsening cholangiopathy has been seen despite abstinence. In patients who present with unexplained cholangiopathy, chronic ketamine use should be considered.Figure 1.: Liver biopsy: A mild lymphoplasmacytic inflammation is noted in some triads with focal and mild interface activity. The bile ducts are injured (irregular contour, unevenly distributed nuclei, intracytoplasmic vacuoles) with focal periportal cholestasis. Immunohistochemical stain for keratin 7 confirms predominantly periportal cholestatic hepatocytes. Keratin 19 shows widespread loss of canals of Hering and focal bile duct loss. Rhodanine stain confirms periportal hepatocellular copper accumulation compatible with a chronic cholestatic process. Table 1. - Patient's hepatic function panels during initial encounter, subsequent encounter, and at least 6 months after subsequent encounter Liver Tests Reference Range & Units Initial Hospitalization Subsequent Hospitalization Most Recent Liver Tests Total bilirubin 0.2 – 1.2 mg/dL 0.8 2.9 4.5 Direct bilirubin 0 – 0.5 mg/dL 0.7 1.8 3.3 Aspartate aminotransferase 5 – 34 IU/L 75 104 88 Alanine transaminase 0 – 37 IU/L 74 129 91 Alkaline phosphatase 40 – 150 IU/L 1017 1106 845 Gamma glutamyl transferase 12 – 43 IU/L 2310 2516 1897

S3074 Lecithin-Cholesterol Acyltransferase Deficiency From Statin-Induced Autoimmune Hepatitis

Introduction: A 65yr female presented to the hospital with complaints of pruritis and fatigue that had been ongoing for two months. Upon admission she was found to have transaminitis with AST and ALT at 392 and 400 respectively. (reference lab values AST 0-37 ; ALT 0-35) along with a total bilirubin of 25.1 mg/dL. (Ref 0-1.2). She reported that 1 month ago she went to a primary care doctor and was started on insulin, a calcium channel blocker and atorvastatin. A liver biopsy was done which revealed subacute liver injury- autoimmune pattern of injury (de novo versus secondary) +/- medication injury. This was confirmed by further positive autoimmune markers suggestive of autoimmune hepatitis. Case Description/Methods: The patient presented to the ER complaining of intense pruritis, dark urine, pale stools, and jaundice. She had recently started atorvastatin, amlodipine and insulin for newly diagnosed diabetes mellitus and essential hypertension. All home medications were stopped at admission except insulin. She had no prior history of liver disease and no family history of liver disease. She did not take any supplements and had never consumed alcohol. Initial labs revealed a transaminitis with AST and ALT at 392 and 400 IU/L respectively. (reference lab values AST 0-37 ; ALT 0-35 )along with alkaline phosphate at 2147 IU/L. (Ref 44-121). Initial imaging with a right upper quadrant ultrasound was normal. Patient continued to have a transaminitis and elevated alkaline phosphate that were not improving. A MRCP was done which showed hepatomegaly, mild periportal edema, slightly heterogenous enhancement-conglomerate of findings suggests nonspecific hepatitis. An EUS liver biopsy was performed which revealed subacute liver injury- autoimmune pattern of injury (de novo versus secondary) +/- medication injury. Additional laboratory testing revealed positive autoimmune markers; pointing to a drug induced autoimmune hepatitis as the likely diagnosis. Discussion: Patient was started on prednisone and discharged on a steroid taper once her liver function tests began to improve. She followed up in liver clinic and was noted to have developed hypercholesteremia with total cholesterol of 1,375 MG/DL (Ref 170-199 MG/DL), LDL of 1220 Mg/DL and HDL of 162 MG/DL. A cholesterol esters assay was ordered and referral for genetic testing made for likely acquired lecithin cholesterol acyltransferase deficiency in the setting of statin induced autoimmune hepatitis. Previous cholesterol tests prior to starting atorvastatin were normal.

S3315 Acute Cholestatic Hepatitis Following m-RNABNT162b2 SARS-CoV-2 Vaccination: Could It Be Genetic?

Introduction: Given the morbidity and mortality of COVID-19, development of vaccines targeting SARs-CoV-2 was essential. Despite their overall safety and efficacy, atypical complications have been reported. We report a case of post-vaccination acute cholestatic hepatitis, consistent with drug-induced liver injury (DILI). Case Description/Methods: A 61-year-old man with no past medical history presented with 2 weeks of jaundice and pruritus, 1 month after his second dose of the m-RNABNT162b2 SARS-CoV-2 vaccine. He denied use of any medications, supplements, tobacco, alcohol, drugs, or family history of liver disease. Vital signs and physical exam were unremarkable. Admission labs included ALP 265 U/L, AST 50 U/L, ALT 68 U/L, total bilirubin 14.9 mg/dL, and direct bilirubin 12 mg/dL. Ultrasound revealed normal liver surface without ductal dilatation, confirmed by MRCP. Serologies (HIV, HAV IgM, HBV core IgM, HBV surface antigen, HCV antibody), autoimmune markers (ANA, anti-mitochondrial, anti-actin, anti-liver-kidney-microsomal), and respiratory viral panel (SARS-CoV-2, influenza A/B, RSV) were negative. Hemoglobin, platelets, INR, albumin, gamma-glutamyl transpeptidase (GGT), and immunoglobulins were normal. Percutaneous liver biopsy revealed cholestasis with mild portal lymphocytic infiltrates and lobular inflammation (Figure 1), without portal fibrosis, PAS+ globules, or iron deposition. Molecular genetic testing (Next Generation Sequencing, Prevention Genetics® 77 Gene Cholestasis Panel) was performed. No genetic variants were identified in 77 genes associated with cholestasis, though single copy variants of several autosomal recessive genes were detected. Symptoms resolved with supportive care. Labs one month later were notable for ALP 175 U/L, (AST hemolyzed), ALT 68 U/L, and total bilirubin 3.2 mg/dL. Discussion: Prior reports have described cholestasis due to immune-mediated hepatitis after COVID mRNA vaccination1, but these features were absent in this case. Given the patient’s normal GGT, we hypothesized that increased cytokine release led to cholestatic injury in an individual genetically predisposed to cholestasis by genetic variation in ATP8B1 or ABCB11. Future studies comparing genetic variants in patients with liver injury may provide insight into mechanisms of idiosyncratic DILI following mRNA vaccination against SARS-CoV-2.Figure 1.: Liver biopsy showing cholestasis in a patient who developed jaundice after COVID mRNA vaccination.

Sero-Prevalence, Infectivity, and Associated Risk Factors of Hepatitis B Virus Among Pregnant Women Attending Antenatal Care in Sankura Primary Hospital, Silte Zone, Southern Ethiopia, 2021

Background: Hepatitis B (HBV) infection causes a major public health problem around the globe. Therefore, this study aimed to assess the Seroprevalence, infectivity, and associated factors of hepatitis B virus infection among pregnant women attending antenatal care in Sankura Primary Hospital, Southern Ethiopia. Methods: A cross-sectional study design was conducted in Sankura Primary Hospital, Southern Ethiopia, from April to June 2020. A total of 338 pregnant women were recruited using systematic random sampling. Sociodemographic and associated risk factors were collected through a structured questionnaire. Blood samples and plasma analysis were performed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen (HBeAg) using the rapid test strip method. Statistical analysis was done using SPSS version 20, and P-value &lt; 0.05 was considered statistically significant. Results: The overall Seroprevalence of HBsAg was 11 (3.3%) [95% CI 1.5% - 5.0%], of whom 2 (18.2%) were positive for HBeAg. In multivariate analysis, a history of blood transfusion [AOR=4.8 95% CI (1.25-6.69)] and contact with a family history of the liver [AOR=5.7 95% CI (1.28-7.9)] was found to be significant predictors of HBV infections. Conclusion: The Seroprevalence of HBV infection among pregnant women in the study area was intermediate. Family history of liver disease and blood transfusion were risk factors associated with HBV infection. Hence, improving the screening of blood, increasing awareness about the transmission of HBV infection, and screening pregnant women for HBV infection should be implemented. The government will build efficient service delivery models equipped with an appropriate and well-trained workforce.

55-Year-Old Man Presenting With Jaundice

A previously healthy 55-year-old man presented to our outpatient clinic with several days of jaundice, pruritus, acholic stools, and dark-colored urine. Three weeks before, he had completed a course of amoxicillin-clavulanic acid for an acute upper respiratory infection. The patient denied excessive alcohol intake, foreign travel, or recent sick contacts. He did not take regular medications or herbal supplements and had no personal or family history of liver disease.

20-Year-Old Man With Elevated Liver Tests

20-Year-Old Man With Elevated Liver Tests

Focal Nodular Hyperplasia-Like Lesion in a Girl with Obesity and Fatty Liver.

Focal Nodular Hyperplasia-Like Lesion in a Girl with Obesity and Fatty Liver.

Non-Cirrhotic Hepatocellular Carcinoma with Duodenal Metastasis in Chronic Hepatitis B: Case Report

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. The extrahepatic extension is also more common in non-cirrhotic HCC. It most commonly metastases to the regional lymph nodes, bone, and lungs. Metastasis to the small bowel is rare. Further, hematogenous metastasis to the duodenum is incredibly rare. Case: A 67-year-old man was admitted with a recurrence of hematemesis melena, weight loss, weakness, and decreased appetite. There was a history of hepatitis and a family history of liver diseases. Abdominal examination revealed a palpable liver (8 cm below the right costal margin, firm, irregular, and tender). Laboratory studies revealed Hb 5.2 g/dL, SGOT 301.1 u/L, SGPT 244.7 u/L, albumin 2.7 g/dL, HbsAg was reactive with HBV DNA 2.01 x 104 IU/ml. EGD showed that esophageal varices were not visible, the duodenum showed an irregular mass, bleeding on touch, and many blood clots. Abdominal USG revealed hepatomegaly with suspicion of multifocal hepatoma, while a CT scan suggested the appearance of HCC and no local invasion into the small bowel. The result of the fibro scan was severe fibrosis, not cirrhosis. At laparotomy, a hepatic tumor and duodenum were discovered. The histopathological study of the tumor revealed a well-differentiated HCC. The resection of the tumor could not be done. He was given palliative and symptom treatment HCC on non-cirrhotic liver remains an exceptional condition. Conclusion: We report a non-cirrhotic HCC in chronic hepatitis B infection.

S2441 Mesalamine-Induced Autoimmune Hepatitis in Patient With Ulcerative Colitis: Case Report

Introduction: Mesalamine is widely considered to be first-line therapy for patients with mild to moderate ulcerative colitis. It is generally well tolerated with usually minor side effects. Mesalamine-induced liver injury is very rarely reported, commonly in the context of multiorgan disease. Isolated mesalamine-induced autoimmune hepatitis has not been reported. Case description/methods: A 53-year-old female with one-month history of bloody diarrhea, decreased appetite, and 10-lb weight loss underwent colonoscopy that confirmed mild to moderate left-sided ulcerative colitis. Blood counts, renal function, and liver function (LFT) were normal and hepatitis B serology was negative. She was started on standard dosing of oral and rectal mesalamine and achieved clinical remission at three months. Five months later, she had abnormal LFT on routine evaluation; alanine aminotransferase (ALT) was 122 IU/L and aspartate aminotransferase (AST) was 44 IU/L, with normal total bilirubin and alkaline phosphatase. She was asymptomatic and denied personal and family history of liver disease. On repeat investigation, ALT peaked at 359 IU/L and AST at 210 IU/L (Figure 1). Serologic evaluation was notable for positive anti-nuclear antibody at 1:640 and positive anti-mitochondrial antibody of 0.5 U. Anti-smooth muscle antibody, acute viral hepatitis panel, and metabolic liver disease markers were normal. Magnetic retrograde cholangiopancreatography (MRCP) noted no abnormalities. Liver biopsy revealed inflammatory infiltrate of lymphocytes and macrophages with scattered eosinophils and plasma cells, consistent with autoimmune hepatitis. One month after discontinuation of mesalamine, liver tests normalized (AST 24 IU/L, ALT 36 IU/L). She maintained a clinical remission and normal at one year follow up after switching to adalimumab. Discussion: A recent UK audit revealed 3.2 cases of mesalamine-induced-liver-injury per million prescriptions, which included asymptomatic transaminitis, cholestatic hepatitis, and granulomatous hepatitis, mostly in the context of systemic, multiorgan disease. This is the first report, to our knowledge, of an isolated mesalamine-induced autoimmune hepatitis in a patient with ulcerative colitis. The diagnosis is strongly supported by characteristic histological findings, positive autoimmunity markers, resolution of injury with discontinuation of drug, and exclusion of other causes. It may be prudent to monitor LFT in ulcerative colitis patients treated with mesalamine.Figure 1.: Trend of transaminases following initiation and discontinuation of mesalamine.

Rates and characteristics for hepatitis B reactivation of inactive hepatitis B carriers in rural communities

Objective: To analyze the intensity and epidemiological characteristics of hepatitis B virus (HBV) reactivation among inactive HBsAg carriers (IHC) of rural areas in Ji'nan. Methods: In 2018 and 2020, follow-up investigations were conducted on IHC identified in the population physical examination in Zhangqiu district of Ji'nan. The results of the two follow-up visits were compared to analyze the incidence and distribution characteristics of HBV reactivation in IHC at the community level. Results: A total of 424 IHC completed two follow-up visits, and 47 cases of HBV reactivation were found, the cumulative reactivation rate was 11.08%, and the incidence density was 5.46/100 person-years. Multivariate analysis showed that gender, age, smoking, drinking , family history of liver disease and chronic diseases were not associated with HBV reactivation (P>0.05), and baseline HBV DNA load was associated with reactivation (P<0.05), in the HBV DNA level ≥1 000 IU/ml group, the reactivation rate could reach 18.92%. After reactivation, the mean level of ALT increased from baseline and the abnormal rate increased, liver function tended to be abnormal in reactivated patients. 4 (8.51%) reactivators had hepatitis, and 1 (2.13%) had jaundice hepatitis. Conclusions: The incidence of HBV reactivation was higher among IHC in rural communities in Ji'nan. Most of the reactivators were asymptomatic or mildly reactivated. Follow-up of inactive HBsAg patients should be strengthened and changes in ALT and HBV DNA levels should be closely monitored.

Proportion of Nonalcoholic Steatohepatitis in Patients with Chronic Liver Disease

Aim: To determine the frequency of nonalcoholic steatohepatitis in patients with liver cirrhosis. Study Design: Retrospective/observational Place and Duration of Study: Department of Medicine, Chandka Medical College Hospital, Larkana from 1st July 2020 to 31st March 2021. Methodology: One hundred and twenty patients of both genders presented with liver cirrhosis were enrolled in this study. Patient’s detailed demographics including age, sex, body mass index, smoking status, alcohol consumption and family history of liver disease were recorded after taking written informed consent. Laboratory examination was done to examine the proportion of hepatitis B virus, hepatitis C virus and nonalcoholic steatohepatitis. Results: There were 68 (56.67%) males and 52 (43.33%) were females with mean age 45.74±10.54 years. Among all the patients hepatitis C virus was found in 62 (51.67%) patients, 15 (12.5%) had hepatitis B virus, 17 (14.17%) had hepatitis B virus + hepatitis C virus and nonalcoholic steatohepatitis was found in 26 (21.67%) patients. Conclusion: Nonalcoholic steatohepatitis was the major cause of liver cirrhosis in Pakistani population. The proportion of NASH in liver cirrhosis patients was 21.67%. Keywords: Nonalcoholic steatohepatitis (NASH), Liver Cirrhosis, Hepatitis B virus, Hepatitis C virus

Perception of Illness and Its Association with Treatment Willingness in Patients with Newly Diagnosed Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease of immense public health relevance. Understanding illness perceptions in the NAFLD population will provide sound scientific evidence for planning high-quality patient-centered care and implementing effective interventions. The Brief Illness Perception Questionnaire (BIPQ) is a robust psychometric tool to systematically assess the dimensions of illness perceptions in various chronic ailments. In a cross-sectional study enrolling patients with newly diagnosed NAFLD, the sociodemographic, anthropometric, biochemical, and radiological determinants of enhanced illness perceptions (measured by the BIPQ score) were investigated using univariate and multivariable binary logistic regression analyses. Finally, the association between individual domains of the BIPQ and willingness to participate in comprehensive medical management was explored. In total, 264 patients (mean age 53 ± 11.9years, 59.8% males) were enrolled in the final analysis. The mean and median BIPQ scores in the study population were 30.3 ± 12.8 and 31.0 (IQR, 22.0-40.0), respectively. The variables having a significant independent association with heightened perceptions (BIPQ > 31) were family history of liver disease (aOR, 5.93; 95% CI, 1.42-24.74), obesity (aOR, 3.33; 95% CI, 1.57-7.05), diabetes mellitus (aOR, 2.35; 95% CI, 1.01-5.49), and transaminitis (aOR, 2.85; 95% CI, 1.42-5.69). Patients with a higher level of illness perceptions (31.6 ± 12.9 vs 27.8 ± 12.3, p = 0.022) were more likely to express a willingness to participate in the comprehensive management plan, with 3 of the 8 domains (consequence, identity, and treatment control) mainly affecting willingness. A family history of liver disease, obesity, diabetes, and transaminitis were independently associated with increased illness perceptions. A belief in serious consequences, a strong illness identity, and higher perceived treatment control were significantly associated with the willingness to undergo comprehensive care for NAFLD.