Scrub typhus, a rare of cause of fulminant hepatic failure: A common disease with uncommon presentation

Scrub typhus (bush typhus) is a potentially lethal mite-borne, acute febrile infectious illness caused by Orientia tsutsugamushi, reported precipitating frequent outbreaks in the Asia-pacific belt. Usual presentation after a median incubation period of 10–14 days, stretches from pathognomonic eschar, high-grade fever, centrifugal skin rash, jaundice, regional lymphadenopathy to frontal headache, nevertheless complicated at times with myocarditis, acute respiratory distress syndrome, acute kidney injury, encephalitis, and shock. Although patients with scrub typhus invariably do display mild liver injury, fulminant hepatic failure (FHF) is rarely reported. We describe herein, a case of FHF in an elderly male that responded well to antibiotics. Early diagnosis and sensitive antibiotic administration aids in mortality prevention of the former.

Investigation of Inherited Chromosomally Integrated Human Herpesvirus-6A+ and -6B+ in a Patient with Ulipristal Acetate-Induced Fulminant Hepatic Failure

Inherited chromosomally integrated (ici) human herpes virus 6 (HHV-6) is estimated to occur in 0.6–2.7% of people worldwide. HHV-6 comprises two distinct species: HHV-6A and HHV-6B. Both HHV-6A and HHV-6B integration have been reported. Several drugs are capable of activating iciHHV-6 in tissues, the consequences of which are poorly understood. We report herein a case of a woman with iciHHV-6A+ and iciHHV-6B+, who developed ulipristal acetate (a selective progesterone receptor modulator)-induced fulminant hepatic failure that required liver transplantation. We confirmed the presence of ~one copy per cell of both HHV-6A and HHV-6B DNA in her hair follicles using multiplex HHV-6A/B real-time PCR and demonstrated the Mendelian inheritance of both iciHHV-6A and iciHHV-6B in her family members over three generations. Because of the rarity of this presentation, we discuss herein the possible links between reactivated HHV-6 from iciHHV-6A and/or iciHHV-6B and adverse drug reactions, suggesting that iciHHV-6 could be screened before the introduction of any hepatotoxic drugs to exclude HHV-6 active disease or combined idiosyncratic drug-induced liver injury in these patients.

GPR120 induces regulatory dendritic cells by inhibiting HK2-dependent glycolysis to alleviate fulminant hepatic failure

Fulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. Using Propionibacterium acnes (P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn’t directly target T cells, but dramatically induced a distinct population of CD11c+MHC IIlowCD80lowCD86low regulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.

A successful initiation of treatment of Hodgkin's lymphoma with adriamycin-bleomycin-vinblastine-dacarbazine dose reduction in a patient with fulminant hepatic failure and co-infection with human immunodeficiency virus and hepatitis B

Introduction Hodgkin lymphoma is a highly curable lymphoproliferative malignancy with an overall relative survival rate of 87.4%. It is characterized by multinucleated Reed–Sternberg cells which are mostly derived from B cells in the germinal center. Case report We present a case of a 40-year-old gentleman with acquired immunodeficiency syndrome who presented with Stage 4b Hodgkin lymphoma complicated with fulminant hepatic failure and direct hyperbilirubinemia. The initial presentation of Hodgkin lymphoma as cholestatic jaundice is extremely rare. Management and outcome Though the survival rate with chemotherapy is high, the fulminant hepatic failure made the situation challenging with the use of chemotherapeutic regimens that require hepatic excretion. He received dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen [doxorubicin 12.5 mg (6.75 mg/m2), bleomycin 18 units (10 units/m2), vinblastine 3 mg (1.5 mg/m2), dacarbazine 380 mg (190 mg/m2)] as well as bictegravir/emtricitabine/tenofovir alafenamide since admission for treatment of human immunodeficiency virus and hepatitis B. He started responding with the first cycle of dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen with bilirubin levels trended down and normalized as well as his clinical condition improved. He received the full dose of adriamycin-bleomycin-vinblastine-dacarbazine on day 15. Discussion Our case report emphasizes that the early usage of dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen can restore hepatic function and can achieve improvement in hepatic function allowing the delivery of full-dose chemotherapy.

Fulminant hepatic failure during pregnancy.

Objective: To observe clinical characteristics, etiology and maternal outcome in fulminant hepatic failure during pregnancy. Study Design: Descriptive Case Series. Setting: Department of Medicine, Nishtar Hospital Multan. Period: January 2013 to December 2017. Material & Methods: Twenty nine consecutive patients with fulminant hepatic failure during pregnancy were included in the study. Results: Mean age of patients was 27.06±6.92 years. 65.51% patients were from urban areas. Mean duration of gestation was 24.80±6.03 weeks. Jaundice and altered consciousness were observed in 100% cases, pallor in 79.31%, hepatomegaly in 20.68%, flapping tremors in 10.34%, ascites in 10.34% and splenomegaly in 6.89% cases. Complications observed were cerebral edema in 44.82%, renal failure in 24.13%, bleeding in 20.68% and hypoglycemia in 3.44%. Most common cause was acute hepatitis E (75.86%) followed by hepatitis B (13.79%) and hepatitis A (3.44%). No cause was found in 6.89% cases. Overall maternal mortality was 37.93% and fetal mortality was 72.41%. In 17.24% cases pregnancy was terminated therapeutically, 44.82% cases had spontaneous expulsion and in 37.93 % cases pregnancy continued. Maternal mortality was highest (45.45%) in patients who remained pregnant as compared to 20% when pregnancy was terminated therapeutically. Conclusion: Jaundice and altered conscious level is the most common clinical presentation. Hepatitis E is the most common cause of FHF in pregnancy. Maternal mortality in FHF during pregnancy is very high.

Fulminant hepatic failure in pregnancy: challenges, management strategies, prognosis and outcomes

Fulminant hepatic failure is defined as a sudden, severe impairment of hepatic function leading to an encephalopathy, which occurs within eight weeks of appearance of first symptoms in the absence of pre-existing liver disease. The spectrum of liver disease in pregnancy may range from mild asymptomatic transaminitis to fatal and irreversible deterioration in liver function leading to significant morbidity and even mortality. Hepatic dysfunction in pregnancy may be categorized into Pre-eclampsia-associated liver diseases such as pre-eclampsia/eclampsia, the HELLP syndrome and Acute fatty liver of pregnancy (AFLP), and other causes of hepatic dysfunction namely Hyperemesis gravidarum (HG) and Intrahepatic cholestasis of pregnancy (IHCP). For this review, a search was conducted for published articles, case reports and clinical trials in MEDLINE/Pubmed from 1970 to 2020 with the keyword’s fulminant hepatic failure, acute liver failure in pregnancy, pre-eclampsia, HELLP and AFLP. We concluded that fulminant hepatic failure is one of the most dreaded complications in pregnancy in obstetrical units worldwide. Mandatory screening for etiology, early diagnosis and initiation of supportive management as soon as possible are absolutely essential to ensure better maternal and fetal outcomes. Effective communication with the obstetrician regarding timely delivery/termination of pregnancy ensures a favourable prognosis in the majority of cases. Liver transplant is a definitive life-saving option for cases of severe fulminant hepatic failure in pregnancy, and management has to be suited to each patient individually, keeping in mind the well-being of both the mother, and the child.

Progesterone-Mediated Enhancement of Hepatitis E Virus Replication in Human Liver Cells

Hepatitis E is usually a self-limiting acute disease; however, during pregnancy, a severe form of fulminant hepatic failure and high mortality rate are associated with hepatitis E virus (HEV) infection. Increased levels of progesterone and HEV RNA are observed in pregnant women with fulminant hepatic failures.