The Pharmacological Effects and Pharmacokinetics of Active Compounds of Artemisia capillaris

Artemisia capillaris Thunb. (A. capillaris, Yin-Chen in Chinese) is a traditional medicinal herb with a wide spectrum of pharmacological properties ranging from effects against liver dysfunction to treatments of severe cirrhosis and cancer. We used relevant keywords to search electronic databases, including PubMed, Medline, and Google Scholar, for scientific contributions related to this medicinal herb and the pharmacokinetics of its components. The pharmaceutical effects of A. capillaris contribute to the treatment not only of viral hepatitis, cirrhosis, and hepatocellular hepatoma, but also metabolic syndrome, psoriasis, and enterovirus in the clinic. The bioactive compounds, including scoparone, capillarisin, scopoletin, and chlorogenic acid, exhibit antioxidant, anti-inflammatory, antisteatotic, antiviral, and antitumor properties, reflecting the pharmacological effects of A. capillaris. The pharmacokinetics of the main bioactive compounds in A. capillaris can achieve a maximum concentration within 1 hour, but only chlorogenic acid has a relatively long half-life. Regarding the use of the A. capillaris herb by health professionals to treat various diseases, the dosing schedule of this herb should be carefully considered to maximize therapeutic outcomes while lessening possible side effects.

Safety and Efficacy of Direct Oral Anticoagulants in Patients With Moderate to Severe Cirrhosis

Background: Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. Objective: To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. Methods: This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. Results: A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group ( P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population ( P = 0.55). No fatal bleeding or thromboembolic events occurred. Conclusion and Relevance: DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

Severe Aplastic Anemia in a Patient with Erythropoietic Protoporphyria Successfully Treated by Avatrombopag

Erythropoietic protoporphyria (EPP) is a rare autosomal recessive disease presented with protoporphyrin deposition, photosensitivity and even liver damage. Avatrombopag, a thrombopoietin receptor agonists, has been applied for immune thrombocytopenia and periprocedural thrombocytopenia in patients with chronic liver disease. Here, we reported the first case of a 19-year-old man with acquired aplastic anemia associated with congenital EPP. EPP has led to a severe cirrhosis and liver dysfunction in this patient, which limited hematopoietic stem cell transplantation and immunosuppressive therapy to cure aplastic anemia. We administered Avatrombopag as the first-line therapy. After 8 months, we observed that avatrombopag induced complete response of aplastic anemia safely.

Colonization with multidrug-resistant organisms impairs survival in patients with hepatocellular carcinoma

Introduction MDRO-colonization has been shown to impair survival in patients with hematological malignancies and solid tumors as well as in patients with liver disease. Despite the increasing spread of multidrug-resistant organisms (MDRO), its impact on patients with hepatocellular carcinoma (HCC) has not been studied. We conducted this retrospective study to analyze the impact of MDRO-colonization on overall prognosis in HCC patients. Materials and methods All patients with confirmed HCC diagnosed between January 2008 and December 2017 at the University Hospital Frankfurt were included in this study. HCC patients with a positive MDRO screening before or within the first 90 days after diagnosis of HCC were defined as colonized HCC patients, HCC patients with a negative MDRO screening were defined as noncolonized HCC patients. Results 59 (6%) colonized and 895 (94%) noncolonized HCC patients were included. Enterobacterales with extended-spectrum β-lactamase-like phenotype with or without resistance to fluoroquinolones (ESBL/ ± FQ) were the most frequently found MDRO with 59%, followed by vancomycin-resistant Enterococcus faecium with 37%. Colonized HCC patients had more severe cirrhosis and more advanced HCC stage compared to noncolonized HCC patients. Colonized HCC patients showed an impaired survival with a median OS of 189 days (6.3 months) compared to a median OS of 1001 days (33.4 months) in noncolonized HCC patients. MDRO-colonization was identified as an independent risk factor associated with survival in multivariate analysis. Conclusion MDRO-colonization is an independent risk factor for survival in patients with HCC highlighting the importance of regular MDRO screening, isolation measures as well as interdisciplinary antibiotic steward-ship programs to guide responsible use of antibiotic agents.

Sorafenib plus partial splenic embolism for treatment of hepatocellular carcinoma Barcelona stage C combined with hypersplenism: a case series

Background Sorafenib is mainly used to treat patients with hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage C, many of whom also have severe cirrhosis. However, hypersplenism and digestive tract hemorrhage are common complications of cirrhosis, which increase the risk and difficulty of treatment. Methods Nineteen patients with HCC BCLC stage C with hypersplenism were treated with sorafenib plus partial splenic embolism at Chongqing University Cancer Hospital, Chongqing, China, between January 2015 and June 2018. We analyzed the therapeutic effect and clinical safety of this treatment in these patients. Result Hypersplenism was rectified in all patients. The incidence rates of hemorrhage and myelosuppression were 0%, and the mean survival time was 11.2 months. Conclusion Sorafenib plus partial splenic embolism could relieve hypersplenism and prolong survival in patients with BCLC stage C HCC.

Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report

Background Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma. Case presentation A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis. Conclusions This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.

Association between osteoporosis and hepatitis B cirrhosis: a case-control study

Background and aims: Hepatitis B virus (HBV)-related cirrhosis is associated with decreased bone mineral density (BMD); however, the mechanism is yet unknown. To assess the incidence of osteoporosis in patients with HBV-associated cirrhosis and relevant mechanisms. Methods: A total of 80 hospitalized patients with HBV-associated cirrhosis and 80 healthy controls were enrolled. The levels of serum osteocalcin, total procollagen type 1 amino-terminal propeptide, β-C-terminal telopeptide of type I collagen (β-CTX), and 25-hydroxy vitamin D3 (25(OH)D3) was evaluated in the cirrhosis group. Results: The BMDs of the lumbar spine (P<0.001) and hip joints (P=0.015) in the cirrhosis group were significantly lower than those in the controls. The incidence of osteoporosis in the cirrhosis group was significantly higher than that in the con- trol group (P<0.001). Compared to the patients of the Child-Pugh grade A and B, the BMD of lumbar spine and 25(OH)D3 was significantly decreased in patients of grade C, while β-CTX was elevated. Patients in the cirrhosis group faced a higher risk of osteoporosis as compared to the controls(P<0.001). Conclusion: Enhanced bone resorption accounted for increased risk of osteoporosis in severe cirrhosis. Thus, HBV-asso- ciated cirrhosis was a risk factor for osteoporosis. Keywords: Liver cirrhosis; bone density; osteoporosis; osteopenia; hepatitis B, chronic.

Abstract P136: Non-alcoholic Fatty Liver Disease Fibrosis Score Predicts The Development Of Carotid Atherosclerosis: The Strong Heart Family Study

Introduction: About 30% of all U.S. adults and 70-80% of those with Type 2 diabetes mellitus (T2DM) have non-alcoholic fatty liver disease (NAFLD). Atherosclerotic cardiovascular disease (CVD) is more common among NAFLD patients, albeit with limited evidence from large prospective studies. Hypothesis: American Indians (AI) with NAFLD would be more likely to develop carotid atherosclerosis given their high prevalence of obesity and T2DM. Methods: The Strong Heart Family Study (SHFS) is a population-based family study of CVD and its risk factors in AI. Participants (n=2786; 59.6% female, mean age 40.8 ±17.3 y) were recruited from 12 tribes in 3 regions: Arizona, North/South Dakota, and Oklahoma. Carotid ultrasound-assessed plaque and plaque score were obtained at the baseline examination in 2001-03, and again in surviving participants (n=2406) from 2006 to 2009. NAFLD prevalence was estimated using hepatic steatosis index (HSI). NAFLD fibrosis score was used to separate NAFLD patients with or without advanced fibrosis. HSI is calculated using serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), BMI, diabetes status, and sex, while the NAFLD fibrosis score is derived from age, BMI, diabetes status, ALT, AST, platelet count, and serum albumin. Plaque progression was defined as any increase in plaque score (0 to 8 carotid segments with plaque) from baseline to the second examination. Frailty model was used in data analyses to account for the relatedness among family members. Results: Mean BMI of participants was 31.3 ± 7.5 kg/m 2 , 19% had T2DM, 32.6% were hypertensive, and 36.3% were current smokers. NAFLD prevalence (HSI > 36) was 78%, while 6% did not have NAFLD (HSI < 30) and 16% participants were in an intermediate category (HSI 30-36). Among participants with NAFLD (n=2096), three fibrosis classes were defined by NAFLD fibrosis scores: 1 no to moderate fibrosis (61%, fibrosis score < -1.455), 2 indeterminate (31%, -1.455 ≤ fibrosis score ≤ 0.676), and 3 cirrhosis or severe cirrhosis (8%, fibrosis score > 0.676). About 31% of participants had carotid atherosclerosis (plaque score ≥ 1) at baseline. About 14% of the 2252 participants who had two carotid ultrasound evaluations had plaque progression and 19% of those without carotid atherosclerosis at baseline (n=1571) had incident plaque at the second visit. Compared to those with no to moderate fibrosis, those who had cirrhosis or severe cirrhosis had higher risks of plaque progression with a hazard ratio (HR, 95% CI) of 1.8 (1.1-2.9, P=0.026), and of incident plaque with a HR (95% CI) of 2.6 (1.5-4.6, P=0.0009), adjusted for sex, smoking, hypertension, albuminuria, LDL-C, and HDL-C. Similar results were found among participants with intermediate fibrosis scores. Conclusions: The prevalence of HSI-defined NAFLD is high in AI. NAFLD fibrosis score predicts both incident and progressive carotid atherosclerosis.

Staging Laparoscopy in Patients with Intrahepatic Cholangiocarcinoma: Is It Still Useful?

<b><i>Background:</i></b> The role of staging laparoscopy in patients with intrahepatic cholangiocarcinoma remains unclear. Despite extensive preoperative imaging, approximately 25% of patients are deemed unresectable at laparotomy due to metastasized disease. The aim of this study was to evaluate the frequency of unresectable disease found at staging laparoscopy and to identify predictors for detecting metastasized intrahepatic cholangiocarcinoma. <b><i>Methods:</i></b> We retrospectively collected records of all patients with intrahepatic cholangiocarcinoma, presenting at our institution from 2008 to 2017. Staging laparoscopy was performed on the suspicion of distant metastases and on indication in larger tumors. The yield and sensitivity of staging laparoscopy was calculated. Reasons for unresectability at staging laparoscopy or laparotomy were recorded. <b><i>Results:</i></b> Among a total of 80 patients with potentially resectable intrahepatic cholangiocarcinoma, 35 patients underwent staging laparoscopy on the suspicion of distant metastases. Unresectable disease was found at staging laparoscopy in 15 patients. Reasons for unresectability were liver metastasis (<i>n</i> = 6), peritoneal metastasis (<i>n</i> = 4), severe cirrhosis (<i>n</i> = 2), locally advanced tumor with satellite lesions (<i>n</i> = 1), and distant lymph node metastasis (<i>n</i> = 2). Considering optimal preoperative imaging, the true yield of staging laparoscopy was 20% (7/35). Two patients did not undergo laparotomy due to progression after staging laparoscopy. Of the remaining 18 patients who underwent laparotomy, 6 patients (30%) had unresectable disease, mostly because of distant metastasis (<i>n</i> = 4). <b><i>Conclusions:</i></b> The role of staging laparoscopy to detect unresectable intrahepatic cholangiocarcinoma is highly dependent on the quality of preoperative imaging. Currently, no accurate selection criteria on imaging exist to select patients with intrahepatic cholangiocarcinoma who potentially benefit from staging laparoscopy.

Cirrhosis, Thrombosis, Finding FaXts about Doses: Dosing of Unfractionated Heparin for Venous Thromboembolism in Cirrhosis

Background: Despite known disease-specific alterations to anti–factor Xa (AXA) levels, the physiological response of patients with cirrhosis to unfractionated heparin (UFH) infusions is not well established in clinical settings. Objective: The purpose of this study was to characterize the dosing and safety profile of UFH in patients with varying degrees of cirrhosis when treated for venous thromboembolism (VTE). Methods: This retrospective observational study was conducted at a single academic medical center in the United States. Patients with a diagnosis of cirrhosis who received UFH infusions for greater than 48 hours for treatment of VTE were included. Comparisons between heparin infusion rates, AXA levels, and safety outcomes based on severity of cirrhosis were made to define differences between those groups. Results: When compared by compensation status or by Child-Turcotte-Pugh (CTP) class, patients with more severe disease trended toward lower initial AXA levels on heparin initiation and higher heparin requirements to achieve therapeutic levels and were significantly less likely to achieve therapeutic levels than patients with less severe disease ( P = 0.001 for compensation, P = 0.017 for CTP). Additionally, bleeding rates were higher in patients with more severe disease, without reaching statistical significance. Conclusion and Relevance: Patients with severe cirrhosis required higher doses of heparin to achieve the same therapeutic AXA levels, but also tended to have higher rates of bleeding compared with less severe cirrhosis. These results represent further evidence of changes in heparin response as cirrhosis severity increases and may suggest that current monitoring methods are suboptimal in this patient population.