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(s): 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 livertransplantation. 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 Presented).

Hepatocellular Carcinoma Presenting as a Clival Mass

Introduction: Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancer and has a poor prognosis. Clivus metastasis is rare with only a few reported cases in the medical literature. We report a case of a patient who presented with clival mass found to have metastatic HCC. Case Description/Methods: A 63-year-old woman presented for neurosurgical evaluation after she was found to have a skull base mass on computerized tomography (CT) of the head at an outside hospital. She endorsed dysphagia for three months, however denied headaches or visual disturbances. A magnetic resonance imaging (MRI) revealed a 5.4 cm by 2.9 cm by 3.6 cm mass in the clivus, which was deemed as the cause of dysphagia (Figure 1a). The patient subsequently underwent an endoscopic transsphenoidal resection of the clival mass. Histopathology from the tissue revealed a hepatoid carcinoma, concerning for metastatic HCC (Figure 1b and 2c). Immunohistochemical strains were positive for hepatocytic marker arginase-1 (Figure 1d). Laboratory studies revealed alpha fetoprotein (AFP) of 56,344 ng/mL, CA-125 of 376 ng/mL, normal B-HCG and carcinoembryonic antigen (CEA). Thereafter, a triple phase CT of the liver revealed two LI-RADS 5 lesions suggestive of HCC as the primary malignancy. Patient's case was discussed at multidisciplinary tumor board with recommendations for systemic immunotherapy with atezolimumab plus bevacizumab and radiation therapy to the clivus. Discussion(s): The incidence of HCC has almost tripled since the 1980s making it the fastest rising cause of cancer related deaths. Metastasis to the brain comprises 0.26% to 2.2% of cases and the skull base is the most rarely affected anatomical site. Although CNS presentation is rare, we may see more neurological manifestations of metastatic HCC with the persistence of chronic hepatitis infections, the rise of metabolic diseases such as NASH, and an increase in alcohol-related liver disease during the COVID-19 pandemic. Although exceedingly rare, metastasis to the clivus should be considered in the differential diagnosis of skull base masses. Despite detection and treatment, prognosis remains poor and emphasis should be placed on consistent HCC surveillance. This case emphasizes that skull masses must be evaluated diligently as they can be the first sign of underlying liver malignancy. Given the morbidity and mortality associated with HCC, recognition of atypical manifestations of HCC can lead to a prompt diagnosis and initiation of life-saving treatment. (Figure Presented).

PREDICTORS OF OUTCOMES OF COVID-19 INFECTION IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)

Introduction COVID-19 has been shown to disproportionately affect patients with metabolic syndrome-associated conditions. Although a few small studies have reported an increased frequency of severe COVID-19 infection in patients with NAFLD, little is known regarding the factors portending adverse outcomes in this group. Given the high and rising prevalence of NAFLD, it is important to identify the predictors of adverse outcomes in this diverse group of patients which was the aim of our study. Study Design We retrospectively studied patients with NAFLD diagnosed with COVID-19 at Community Medical Centers in Fresno, California between March 1 and September 30, 2020. Baseline demographics, medications, laboratory values during COVID-19, and baseline liver fibrosis scores prior to admission along with measured outcomes of severity were collected. Scores studied were NAFLD Fibrosis Score (NFS), AST to Platelet Ratio Index (APRI), fibrosis-4 (FIB-4), and MELD-Na. To assess correlations and associations, Chi-square tests, Independent sample t-tests and Pearson correlation testing were used. Results Patients over 18 years of age with NAFLD and PCR-confirmed COVID-19 were included in the study (n=298). Demographics: 71% Hispanic, 52% male, 72% government insurance, mean age 55 years. Outcomes: 83% hospitalized, 74% required supplemental oxygen, 30% required non-invasive positive pressure ventilation (NIPPV), 25% admitted to the intensive care unit (ICU), 15% required intubation and 13% required vasopressors. COVID-19 related mortality rate was 14%. Risk factors for adverse outcomes: Peak AST, ALT, and total bilirubin levels during COVID-19 had statistically significant positive correlations with ICU admission, intubation, and death. Albumin and platelet levels had statistically significant negative correlations with ICU admission, intubation, and death. Albumin had the strongest correlation of-0.431 to -0.497. Chronic proton pump inhibitor (PPI) use had a statistically significant positive correlation with intubation and ICU admission and chronic ACE-inhibitor use with the outcome of death. (Figure 1). Increasing baseline liver fibrosis scores (NFS, APRI, FIB-4) were associated with worse outcomes for hospitalization, oxygen requirement, NIPPV, ICU admission, intubation and death (Figure 2). Discussion Based on our study, patients with NAFLD with elevated baseline liver fibrosis scores, elevated ALT, AST, total bilirubin, and decreased albumin and platelets during COVID-19 are at a significantly elevated risk for adverse outcomes. NFS, APRI, and FIB-4 scores appeared superior to MELD-Na in predicting outcomes. Chronic PPI and ACEinhibitor use are associated with adverse outcomes, and thus should be used with caution in patients with NAFLD during COVID-19 pandemic. Clinicians should be aware of these risk factors while evaluating patients with COVID-19 and NAFLD. $Φgure

Unprecedented rise in alcohol-related hepatitis during COVID-19 pandemic

Background: The third leading preventable cause of death in the United States is excessive alcohol use. Our study sought to assess the impact COVID-19 has had on hospitalizations for alcohol-related hepatitis at a community hospital system. We hypothesized an increase in cases of alcohol-related hepatitis requiring inpatient management in parallel with the economic strain imposed by the COVID-19 pandemic. Methods: The third leading preventable cause of death in the United States is excessive alcohol consumption. Our study sought to assess the impact of the COVID-19 on hospitalizations for alcohol-related hepatitis at a community hospital system. We hypothesized an increase in cases of alcohol-related hepatitis requiring inpatient management in parallel with the strain on the economic and societal norms imposed by the COVID-19 pandemic. Results: There was a 51% increase in the overall incidence of alcohol-related hepatitis requiring hospitalization between 2019 and 2020 (p=0.003), and 69% increase(p<0.001) after implementation of the stay-at-home orders. Additionally, 94%(p=0.028) increase in re-hospitalizations was noted in 2020 (p=0.028), a 100% increase in patients under the age of 40 (p=0.0028) as well as a trend towards a 125% increase (p=0.06) of female patients admitted with this diagnosis during the COVID-19 . Conclusion: Our study revealed drastic increases in severe alcohol-related hepatitis requiring inpatient management specifically in patients under the age of 40 and in females during the COVID-19 pandemic. Given the high morbidity and mortality associated with severe alcohol-related hepatitis, these findings have far reaching and lasting implications for our already strained healthcare system extending beyond the COVID-19 pandemic timeframe. Urgent public health interventions are needed to combat the rising misuse of alcohol and its consequences.