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Sasaki-Tanaka R, Kanda T, Yokoo T, Abe H, Hayashi K, Sakamaki A, Kamimura H, Terai S. Hepatitis A and E Viruses Are Important Agents of Acute Severe Hepatitis in Asia: A Narrative Review. Pathogens 2025; 14:454. [PMID: 40430774 PMCID: PMC12114595 DOI: 10.3390/pathogens14050454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/25/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025] Open
Abstract
Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are severe hepatitis that occur in patients with and without chronic liver diseases and/or cirrhosis, respectively, and both often result in death. Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can cause these severe conditions. We reviewed the role of HAV and HEV, which infect humans through the fecal-oral route, in ALF and ACLF in Asian countries. This narrative review was the derived from a traditional non-systematic review. Hepatitis A should be recognized as one of the sexually transmitted infections, especially among men who have sex with men. HAV genotype IIIA infection seems to present a more severe clinical manifestation. Acute HEV-1 infection is associated with ALF in pregnant women in India. HEV-4, rather than HEV-3, was found in severe hepatitis in Japan. HEV also plays a role as a cause of acute insult and/or chronic liver disease in immunocompromised patients with ACLF. Further studies are needed for the development of vaccines and antivirals against HAV and HEV infections. Despite the limitations of the recording of cases and the extent of specific vaccinations, multidisciplinary cooperation, involving hepatologists, virologists, experts in public health, etc., may improve the treatment of HAV and HEV infection.
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Affiliation(s)
- Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
- Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Uonuma Kikan Hospital, Minami-Uonuma, Niigata 949-7302, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Kazunao Hayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8520, Japan; (R.S.-T.); (T.Y.); (H.A.); (K.H.); (A.S.); (H.K.); (S.T.)
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Roy A, Kumar K, Premkumar M, Sree A, Gupta A, Sharma M, Alla M, Iyengar S, Venishetty S, Ghoshal UC, Goenka M, Rao PN, Saraswat VA, Reddy ND, Kulkarni AV, Reddy RK. Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres. Indian J Gastroenterol 2025; 44:47-56. [PMID: 39112909 DOI: 10.1007/s12664-024-01634-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 06/12/2024] [Indexed: 02/23/2025]
Abstract
BACKGROUND AND AIMS Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. METHODS A multicentre retrospective study across four major tertiary care centres. RESULTS As many as 183 ALF patients (median age, 23 years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen per cent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. CONCLUSIONS Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.
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Affiliation(s)
- Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Karan Kumar
- Department of Hepatology, Mahatma Gandhi Medical College, Jaipur, 302 022, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Amarthya Sree
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Anand Gupta
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Mithun Sharma
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Manasa Alla
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Sowmya Iyengar
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Shantan Venishetty
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Uday C Ghoshal
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Mahesh Goenka
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Padaki Nagaraja Rao
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Vivek Anand Saraswat
- Department of Hepatology, Mahatma Gandhi Medical College, Jaipur, 302 022, India
| | - Nageshwar Duvvur Reddy
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India
| | - Anand V Kulkarni
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, 500 032, India.
| | - Rajender K Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
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Biswas S, Shalimar. Definitions, etiopathogenesis and epidemiology of ALF. Best Pract Res Clin Gastroenterol 2024; 73:101959. [PMID: 39709214 DOI: 10.1016/j.bpg.2024.101959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/22/2024] [Indexed: 12/23/2024]
Abstract
Acute liver failure (ALF) is a rare but preventable cause of acute hepatic dysfunction which is associated with significant mortality, unless treated appropriately. There are significant regional variations in the etiologies of ALF globally and this determines the outcomes of the disease as well as the long-term survival in patients receiving liver transplantation for management. Improvements in understanding of disease pathophysiology and critical care medicine have led to better outcomes over the last few decades. Despite this, the burden of indeterminate ALF and the pathogenesis of many etiological agents are yet to be fully known. Improvements in diagnostic and prognostic modalities are expected to decrease the morbidity and mortality associated with ALF. Changes in vaccination programs and stronger legislative practices regarding over-the-counter sale of acetaminophen and non-proprietary drugs are expected to reduce the burden of disease globally.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
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Biswas S, Kumar R, Shalimar, Acharya SK. Viral hepatitis-induced acute liver failure. Indian J Gastroenterol 2024; 43:312-324. [PMID: 38451383 DOI: 10.1007/s12664-024-01538-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 01/18/2024] [Indexed: 03/08/2024]
Abstract
Viral hepatitis-induced acute liver failure (ALF) is a preventable cause for liver-related mortality worldwide. Viruses are the most common cause for ALF in developing nations in contrast to the west, where acetaminophen is largely responsible. Viruses may be hepatotropic or affect the liver secondary to a systemic infection. In tropical countries, infections such as leptospirosis, scrub typhus and malaria can mimic the symptoms of ALF. Differentiating these ALF mimics is crucial because they require etiology-specific therapy. Treatment of viral hepatitis-induced ALF is two-pronged and directed towards providing supportive care to prevent organ failures and antiviral drugs for some viruses. Liver transplantation (LT) is an effective modality for patients deteriorating despite adequate supportive care. Early referral and correct identification of patients who require a transplant are important. Liver support devices and plasma exchange have evolved into "bridging modalities" for LT. Preventive strategies such as hand hygiene, use of clean and potable water and inclusion of vaccines against viral hepatitis in the national program are simple yet very effective methods focusing on the preventive aspect of this disease.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, 801 507, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India.
| | - Subrat Kumar Acharya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India
- KIIT University, Bhubaneswar, 751 024, India
- Fortis Escorts Digestive and Liver Institute, Okhla, New Delhi, 110 025, India
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Roy A, Ghoshal UC, Kulkarni AV, Lohia K, Tiwary I, Tiwari S, Tewari A, Sonthalia N, Goenka MK. Determinants, profile and outcomes of hepatitis A virus-associated severe acute liver injury in adults. Indian J Gastroenterol 2024; 43:505-512. [PMID: 38664345 DOI: 10.1007/s12664-024-01577-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 03/19/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND AND OBJECTIVES Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF. METHODS This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression. RESULTS Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18-24.5] vs. 31.5 [26-42]), arterial lactate (2.1 [1.3-3.1] vs. 6.3 [5.2-8.0]), arterial ammonia (94 [72-118] vs. 299 [188-573]), procalcitonin (0.5 [0.28-1.25] vs. 3.2 [1.2-6.1]) and ferritin (482 [213-1633] vs. 5186 [1341-11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01-1.06]) and leukocyte count (OR 1.00 [1.00-1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64-0.93) (p = 0.009) (cut-off of 144 μmol/L). Additional comorbidities did not impact overall outcomes. CONCLUSION HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies.
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Affiliation(s)
- Akash Roy
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, 500 082, India
| | - Kautuk Lohia
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Indrajeet Tiwary
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Subhash Tiwari
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Awanish Tewari
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Nikhil Sonthalia
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India
| | - Mahesh K Goenka
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, 700 054, India.
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Kanda T, Sasaki-Tanaka R, Ishii K, Suzuki R, Inoue J, Tsuchiya A, Nakamoto S, Abe R, Fujiwara K, Yokosuka O, Li TC, Kunita S, Yotsuyanagi H, Okamoto H. Recent advances in hepatitis A virus research and clinical practice guidelines for hepatitis A virus infection in Japan. Hepatol Res 2024; 54:4-23. [PMID: 37906585 DOI: 10.1111/hepr.13983] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 10/06/2023] [Accepted: 10/23/2023] [Indexed: 11/02/2023]
Abstract
In 2018, there was a hepatitis A outbreak in Japan, and hepatitis A virus (HAV) infection is considered a sexually transmitted disease. In general, patients with hepatitis A should be given attention, and this disease should be prevented more than ever. The Japan Agency for Medical Research and Development (AMED) Hepatitis A and E viruses (HAV and HEV) Study Group has worked on the project to create "Recent Advances in Hepatitis A Virus (HAV) Research and Clinical Practice Guidelines for HAV Infection in Japan". The group consists of expert hepatologists and virologists who gathered at virtual meeting on August 5, 2023. Data about the pathogenesis, infection routes, diagnosis, complications, several factors for the severities, vaccination, and current and future treatments for hepatitis A were discussed and debated for a draft version. The participants assessed the quality of cited studies. The finalized recommendations are presented in this review. The recent advances in HAV research and clinical practice for HAV infection in Japan, have been reviewed by the AMED HAV and HEV Study Group.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Koji Ishii
- Department of Quality Assurance and Radiological Protection, National Institute of Infectious Diseases, Tokyo, Japan
| | - Ryosuke Suzuki
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ryuzo Abe
- Department of Emergency Medicine, Oita University, Yufu, Oita, Japan
| | - Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tian-Cheng Li
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Satoshi Kunita
- Center for Experimental Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Department of Infectious Diseases and Applied Immunology, Hospital of the Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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Park GC, Chung JW, Jang ES, Kim JW. Association between adverse outcomes of hepatitis A and acetaminophen use: A population-based cohort study. Dig Liver Dis 2023; 55:1368-1374. [PMID: 37088594 DOI: 10.1016/j.dld.2023.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 03/24/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023]
Abstract
BACKGROUND Acetaminophen (APAP) may cause acute liver injury with therapeutic doses in high-risk conditions such as chronic alcohol consumption or malnutrition. In acute hepatitis A (AHA), however, the safety of APAP has not been fully established. This study examined the potential association between APAP use and clinical outcomes of AHA in a nationwide and hospital-based cohort. METHODS Adult patients with AHA were identified from claims data of South Korean national healthcare insurance between 2008 and 2016 (n = 43,500). Logistic regression models were used to compare the risk of adverse outcomes (renal replacement therapy, hepatic encephalopathy and/or brain edema, mechanical ventilation, and liver transplantation) in patients exposed to APAP against control and patients exposed to NSAIDs. A propensity score (PS)-matched hospital-based AHA cohort (n = 146) was assessed for biochemical profiles after exposure to APAP or NSAIDs. RESULTS AHA patients were exposed to APAP or NSAIDs in 26.4% and 11.5% of cases, respectively. Compared to NSAID treatment, APAP exposure was associated with a higher incidence of hospitalization (98.8% vs. 92.4%; p < 0.0001). APAP exposure was independently associated with increased adverse outcomes (odds ratio [OR] = 5.66, p < 0.0001 against control; OR =1.67, p = 0.0015 against NSAIDs). PS-matched hospital cohort showed higher peak serum bilirubin levels (7.0 vs. 5.3 mg/dL; p = 0.03) and a longer time to recovery of jaundice after APAP use than with NSAID use. CONCLUSION APAP exposure was associated with increased adverse outcomes in a nationwide AHA cohort.
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Affiliation(s)
- Gi Chan Park
- Health Insurance Review and Assessment Service, Wonju, Republic of Korea
| | - Jung Wha Chung
- Department of Internal Medicine, Wonkwang University Sanbon Hospital, Republic of Korea
| | - Eun Sun Jang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Biswas S, Shalimar. Liver Transplantation for Acute Liver Failure- Indication, Prioritization, Timing, and Referral. J Clin Exp Hepatol 2023; 13:820-834. [PMID: 37693253 PMCID: PMC10483009 DOI: 10.1016/j.jceh.2023.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 01/17/2023] [Indexed: 09/12/2023] Open
Abstract
Acute liver failure (ALF) is a major success story in gastroenterology, with improvements in critical care and liver transplant resulting in significant improvements in patient outcomes in the current era compared to the dismal survival rates in the pretransplant era. However, the ever-increasing list of transplant candidates and limited organ pool makes judicious patient selection and organ use mandatory to achieve good patient outcomes and prevent organ wastage. Several scoring systems exist to facilitate the identification of patients who need a liver transplant and would therefore need an early referral to a specialized liver unit. The timing of the liver transplant is also crucial as transplanting a patient too early would lead to those who would recover spontaneously receiving an organ (wastage), and a late decision might result in the patient becoming unfit for transplant (delisted) or have an advanced disease which would result in poor post-transplant outcomes. The current article reviews the indications and contraindications of liver transplant in ALF patients, the various prognostic scoring systems, etiology-specific outcomes, prioritization and timing of referral.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India
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Sasaki-Tanaka R, Shibata T, Moriyama M, Kogure H, Hirai-Yuki A, Okamoto H, Kanda T. Masitinib Inhibits Hepatitis A Virus Replication. Int J Mol Sci 2023; 24:9708. [PMID: 37298659 PMCID: PMC10253910 DOI: 10.3390/ijms24119708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/12/2023] Open
Abstract
The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection.
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Affiliation(s)
- Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.S.); (M.M.); (H.K.)
| | - Toshikatsu Shibata
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.S.); (M.M.); (H.K.)
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.S.); (M.M.); (H.K.)
| | - Hirofumi Kogure
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.S.); (M.M.); (H.K.)
| | - Asuka Hirai-Yuki
- Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan;
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan;
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.S.); (M.M.); (H.K.)
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Salajegheh F, Shafieipour S, Najminejad Z, Pourzand P, Nakhaie M, Jahangiri S, Sarmadian R, Gilani A, Rukerd MRZ. HAV-induced acalculous cholecystitis: A case report and literature review. Clin Case Rep 2023; 11:e7254. [PMID: 37113636 PMCID: PMC10127462 DOI: 10.1002/ccr3.7254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 04/02/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Hepatitis A virus (HAV) has some life-threatening extrahepatic complications, such as acute acalculous cholecystitis (AAC). We present HAV-induced AAC in a young female, based on clinical, laboratory, and imaging findings, and conduct a literature review. The patient became irritable, which progressed to lethargy, as well as a significant decline in liver function, indicating acute liver failure (ALF). She was immediately managed in the intensive care unit with close airway and hemodynamic monitoring after being diagnosed with ALF (ICU). The patient's condition was improving, despite only close monitoring and supportive treatment with ursodeoxycholic acid (UDCA) and N-acetyl cysteine (NAC).
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Affiliation(s)
- Faranak Salajegheh
- Clinical Research Development Unit, School of MedicineAfzalipour Hospital, Kerman University of Medical SciencesKermanIran
| | - Sara Shafieipour
- Physiology Research Center, Institute of NeuropharmacologyKerman University of Medical SciencesKermanIran
| | - Zohre Najminejad
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology SciencesKerman University of Medical Sciences KermanKermanIran
| | - Pouria Pourzand
- School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Mohsen Nakhaie
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
| | - Samaneh Jahangiri
- Clinical Research Development Unit, School of MedicineAfzalipour Hospital, Kerman University of Medical SciencesKermanIran
| | - Roham Sarmadian
- Infectious disease research centerArak University of Medical SciencesArakIran
| | - Abolfazl Gilani
- Department of pediatric surgeryTehran university of Medical SciencesTehranIran
| | - Mohammad Rezaei Zadeh Rukerd
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
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11
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Biswas S, Kumar R, Acharya SK, Shalimar. Prognostic Scores in Acute Liver Failure Due to Viral Hepatitis. Diagnostics (Basel) 2023; 13:1035. [PMID: 36980341 PMCID: PMC10047191 DOI: 10.3390/diagnostics13061035] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023] Open
Abstract
Viral infections are among the major causes of acute liver failure (ALF) worldwide. While the role of agents such as hepatitis A, B, C, D and E viruses in precipitating ALF are well known, improvements in serological assays have led to the detection of viral agents such as Epstein Barr virus, cytomegalovirus etc. as atypical causes of ALF. Despite the plethora of literature available on viral hepatitis and ALF, there is very limited large-scale epidemiologic data on the prevalence, risk factors of progression and outcomes in ALF of viral causes. This is important as viral infections remain the leading cause of ALF in the East and in developing countries, while the impact of viral ALF in the West has largely been ameliorated by effective vaccination and sanitization programs. This review focuses specifically on the available prognostic scores that aid in the management of ALF of viral etiologies while also briefly reviewing the current literature on newer viral agents known to cause ALF, risk factors of progression, outcomes and how management algorithms can be developed by incorporation of prognostic scoring systems for referral and transplant listing.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Bihar 801507, India
| | | | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
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12
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Kim JD. [Acute Liver Failure: Current Updates and Management]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 81:17-28. [PMID: 36695063 DOI: 10.4166/kjg.2022.148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 12/25/2022] [Accepted: 12/29/2022] [Indexed: 01/26/2023]
Abstract
Acute liver failure (ALF) is a rare disease condition with a dynamic clinical course and catastrophic outcomes. Several etiologies are involved in ALF. Hepatitis A and B infections and indiscriminate use of untested herbs or supplemental agents are the most common causes of ALF in Korea. Noninvasive neurological monitoring tools have been used in patients with ALF in recent times. Ongoing improvements in intensive care, including continuous renal replacement therapy, therapeutic plasma exchange, vasopressor, and extracorporeal membrane oxygenation, have reduced the mortality rate of patients with ALF. However, liver transplantation is still the most effective treatment for patients with intractable ALF. There is a need for further research in the areas of better prognostication and precise selection of patients for emergency transplantation.
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Affiliation(s)
- Jin Dong Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
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13
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Wang J, Liu PH, Xu P, Sumarsono A, Rule JA, Hedayati SS, Lee WM. Hypochloremia as a novel adverse prognostic factor in acute liver failure. Liver Int 2022; 42:2781-2790. [PMID: 36203349 PMCID: PMC10668517 DOI: 10.1111/liv.15449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 09/05/2022] [Accepted: 10/06/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America. METHODS The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT). RESULTS Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28). CONCLUSIONS Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.
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Affiliation(s)
- Jiexin Wang
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Po-Hong Liu
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Pin Xu
- Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Andrew Sumarsono
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Hospital Medicine, Parkland Memorial Hospital, Dallas, Texas, USA
| | - Jody A. Rule
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - S. Susan Hedayati
- Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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14
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Jindal A, Sarin SK. Epidemiology of liver failure in Asia-Pacific region. Liver Int 2022; 42:2093-2109. [PMID: 35635298 DOI: 10.1111/liv.15328] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 02/13/2023]
Abstract
The global burden of deaths caused by liver failure is substantial. The Asia-Pacific region is home to more than half of the global population and accounted for 62.6% of global deaths because of liver diseases in 2015. The aetiology of liver failure varies in different countries at different times. Viruses (Hepatitis A, B and E), drugs (herbs and anti-tuberculous drugs), toxins (alcohol use) and autoimmune flares are mainly responsible of majority of liver failure in individuals with normal liver (acute liver failure; ALF); else these may precipitate liver failure in those with chronic liver disease (acute-on-chronic liver failure; ACLF). Concomitant increases in alcohol misuse and metabolic syndrome in recent years are concerning. Ongoing efforts to address liver failure-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. In light of the ever-changing nature of liver disease epidemiology, accurate estimates for the burden of liver failure across the countries are vital for setting clinical, research and policy priorities. In this review, we aimed to describe the current as well as changing epidemiological trends of common liver failure syndromes, ALF and ACLF in the Asia-Pacific region.
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Affiliation(s)
- Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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15
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Odenwald MA, Paul S. Viral hepatitis: Past, present, and future. World J Gastroenterol 2022; 28:1405-1429. [PMID: 35582678 PMCID: PMC9048475 DOI: 10.3748/wjg.v28.i14.1405] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 03/04/2022] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
Each hepatitis virus-Hepatitis A, B, C, D, E, and G-poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C. These therapeutic breakthroughs are transforming the fields of hepatology, transplant medicine in general, and public and global health. Most notably, there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade. While attainable, there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local, national, and international scales. Herein, we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.
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Affiliation(s)
- Matthew August Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, University of Chicago, Chicago, IL 60637, United States
| | - Sonali Paul
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, University of Chicago, Chicago, IL 60637, United States
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16
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Cao G, Jing W, Liu J, Liu M. The global trends and regional differences in incidence and mortality of hepatitis A from 1990 to 2019 and implications for its prevention. Hepatol Int 2021; 15:1068-1082. [PMID: 34345993 PMCID: PMC8514357 DOI: 10.1007/s12072-021-10232-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/01/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND PURPOSE Despite decades of improved sanitation and hygiene measures and vaccine introduction, hepatitis A has been spread through numerous outbreaks globally. We used data from the Global Burden of Disease (GBD) study to quantify hepatitis A burden at the global, regional and national levels. METHODS Annual incident cases, deaths, age-standardized incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of hepatitis A between 1990 and 2019 were derived from the GBD study 2019. Percentage changes of cases and deaths, and estimated annual percentage changes (EAPCs) of ASIRs and ASMRs were calculated to quantify their temporal trends. RESULTS Global hepatitis A incident cases increased by 13.90% from 139.54 million in 1990 to 158.94 million in 2019. ASIR of hepatitis A remained stable (EAPC = 0.00, 95% CI -0.01 to 0.01), whereas ASMR decreased (EAPC = -4.63, 95% CI -4.94 to -4.32) between 1990 and 2019. ASIR increased in low (EAPC = 0.09, 95% CI 0.04 to 0.14) and low-middle (EAPC = 0.04, 95% CI 0.03 to 0.06) socio-demographic index (SDI) regions. For GBD regions, the most significant increases of ASIR were detected in high-income Asia Pacific (EAPC = 0.53, 95% CI 0.41 to 0.66), Oceania (EAPC = 0.31, 95% CI 0.25 to 0.36), and Australasia (EAPC = 0.28, 95% CI 0.13 to 0.44). EAPC of ASIR was positively associated with SDI value in countries and territories with SDI value ≥ 0.7 (ρ = -0.310, p < 0.001). CONCLUSION There is an unfavorable trend that hepatitis A is still pending in hyperendemic regions and is emerging in low endemic regions. These highlight the need of targeted and specific strategies to eliminate hepatitis A, such as sanitation measures and a comprehensive plan for surveillance and vaccination against hepatitis A.
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Affiliation(s)
- Guiying Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China.
| | - Wenzhan Jing
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China
| | - Jue Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China
| | - Min Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China.
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17
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Torre P, Aglitti A, Masarone M, Persico M. Viral hepatitis: Milestones, unresolved issues, and future goals. World J Gastroenterol 2021; 27:4603-4638. [PMID: 34366625 PMCID: PMC8326259 DOI: 10.3748/wjg.v27.i28.4603] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.
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Affiliation(s)
- Pietro Torre
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
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Hofmeister MG, Xing J, Foster MA, Augustine RJ, Burkholder C, Collins J, McBee S, Thomasson ED, Thoroughman D, Weng MK, Spradling PR. Factors Associated With Hepatitis A Mortality During Person-to-Person Outbreaks: A Matched Case-Control Study-United States, 2016-2019. Hepatology 2021; 74:28-40. [PMID: 33217769 PMCID: PMC11017379 DOI: 10.1002/hep.31645] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 10/19/2020] [Accepted: 11/05/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A. APPROACH AND RESULTS To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (P < 0.05) higher odds of mortality were associated with preexisting nonviral liver disease (adjusted odds ratio [aOR], 5.2), history of hepatitis B (aOR, 2.4), diabetes (aOR, 2.2), and cardiovascular disease (aOR, 2.2), as well as initial Model for End-Stage Liver Disease (MELD) score ≥ 30 (aOR, 10.0), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 2 (aOR, 10.3), and platelet count < 150,000/μL (aOR, 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex). CONCLUSIONS Preexisting liver disease, diabetes, cardiovascular disease, and initial MELD score ≥ 30, AST/ALT ratio ≥ 1, and platelet count < 150,000/μL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the recommendation of the Advisory Committee on Immunization Practices to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered.
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Affiliation(s)
- Megan G. Hofmeister
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Jian Xing
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Monique A. Foster
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Ryan J. Augustine
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Cole Burkholder
- Division of Communicable Diseases, Michigan Department of Health and Human Services, Lansing, MI
| | - Jim Collins
- Division of Communicable Diseases, Michigan Department of Health and Human Services, Lansing, MI
| | - Shannon McBee
- Bureau for Public Health, West Virginia Department of Health and Human Resources, Charleston, WV
| | - Erica D. Thomasson
- Bureau for Public Health, West Virginia Department of Health and Human Resources, Charleston, WV
- Career Epidemiology Field Officer Program, Division of State and Local Readiness, Centers for Disease Control and Prevention, Atlanta, GA
| | - Douglas Thoroughman
- Career Epidemiology Field Officer Program, Division of State and Local Readiness, Centers for Disease Control and Prevention, Atlanta, GA
- Kentucky Department for Public Health, Frankfort, KY
| | - Mark K. Weng
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Philip R. Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
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19
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Chen H, Li L, Qin P, Xiong H, Chen R, Zhang M, Jiang Q. A 4-gene signature predicts prognosis of uterine serous carcinoma. BMC Cancer 2021; 21:154. [PMID: 33579221 PMCID: PMC7881619 DOI: 10.1186/s12885-021-07834-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 11/19/2020] [Indexed: 12/29/2022] Open
Abstract
Background Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Methods USC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets. Results We uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4-gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC. Conclusions Our findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-07834-4.
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Affiliation(s)
- Hui Chen
- Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.,Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Lingjun Li
- Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ping Qin
- Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Hanzhen Xiong
- Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ruichao Chen
- Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Minfen Zhang
- Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qingping Jiang
- Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
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20
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Li Y, Zhang Y, Fang Q, Zhang X, Hou P, Wu H, Wang X. Radiomics analysis of [ 18F]FDG PET/CT for microvascular invasion and prognosis prediction in very-early- and early-stage hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2021; 48:2599-2614. [PMID: 33416951 DOI: 10.1007/s00259-020-05119-9] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 11/15/2020] [Indexed: 12/16/2022]
Abstract
As a reliable preoperative predictor for microvascular invasion (MVI) and disease-free survival (DFS) is lacking, we developed a radiomics nomogram of [18F]FDG PET/CT to predict MVI status and DFS in patients with very-early- and early-stage (BCLC 0, BCLC A) hepatocellular carcinoma (HCC). METHODS Patients (N = 80) with BCLC0-A HCC who underwent [18F]FDG PET/CT before surgery were enrolled in this retrospective study and were randomized to a training cohort and a validation cohort. Texture features from patients obtained using Lifex software in the training cohort were subjected to LASSO regression to select the most useful predictive features of MVI and DFS. Then, the radiomics nomogram was constructed using the radiomics signature and clinical features and further validated. RESULTS To predict MVI, the [18F]FDG PET/CT radiomics signature consisted of five texture features from the PET and six texture features from CT. The signature was significantly associated with MVI status in the training cohort (P = 0.001). None of the clinical features was independent predictors for MVI status (P > 0.05). The area under the curve value of the M-PET/CT model was 0.891 (95% CI: 0.799-0.984) in the training cohort and showed good discrimination and calibration. To predict DFS, the [18F]FDG PET/CT radiomics nomogram (D-PET/CT model) and a clinicopathologic nomogram were built in the training cohort. The D-PET/CT model, which integrated the D-PET/CT radiomics signature with INR and TB, provided better predictive performance (C-index: 0.831, 95% CI: 0.761-0.900) and larger net benefits than the simple clinical model, as determined by decision curve analyses. CONCLUSION The newly developed [18F]FDG PET/CT radiomics signature was an independent biomarker for the estimation of MVI and DFS in patients with very-early- and early-stage HCC. Moreover, PET/CT nomogram, which incorporated the radiomics signature of [18F]FDG PET/CT and clinical risk factors in patients with very-early- and early-stage HCC, performed better for individualized DFS estimation, which might enable a step forward in precise medicine.
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Affiliation(s)
- Youcai Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Yuexiu District, Guangzhou, 510000, Guangdong, China
| | - Yin Zhang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong Province, China
| | - Qi Fang
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Yuexiu District, Guangzhou, 510000, Guangdong, China
| | - Xiaoyao Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Yuexiu District, Guangzhou, 510000, Guangdong, China
| | - Peng Hou
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Yuexiu District, Guangzhou, 510000, Guangdong, China
| | - Hubing Wu
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong Province, China.
| | - Xinlu Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Road, Yuexiu District, Guangzhou, 510000, Guangdong, China.
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Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease. Int J Mol Sci 2020; 21:ijms21176384. [PMID: 32887515 PMCID: PMC7504211 DOI: 10.3390/ijms21176384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 08/23/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes acute-on-chronic liver failure (ACLF) and non-ACLF. In this review, we searched the literature concerning the association between HAV infection and chronic liver diseases in PubMed. Chronic liver diseases, such as metabolic associated fatty liver disease and alcoholic liver disease, coinfection with other viruses, and host genetic factors may be associated with severe hepatitis A. It is important to understand these conditions and mechanisms. There may be no etiological correlation between liver failure and HAV infection, but there is an association between the level of chronic liver damage and the severity of acute-on-chronic liver disease. While the application of an HAV vaccination is important for preventing HAV infection, the development of antivirals against HAV may be important for preventing the development of ACLF with HAV infection as an acute insult. The latter is all the more urgent given that the lives of patients with HAV infection and a chronic liver disease of another etiology may be at immediate risk.
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Hepatitis A: Epidemiology, Natural History, Unusual Clinical Manifestations, and Prevention. Gastroenterol Clin North Am 2020; 49:191-199. [PMID: 32389358 PMCID: PMC7883407 DOI: 10.1016/j.gtc.2020.01.002] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis A virus (HAV) is a positive-strand RNA virus that is transmitted feco-orally through person-to-person contact. Outbreaks are often linked to poor sanitation, overcrowding, or food and water contamination. Infection is often asymptomatic in children, but adults present with jaundice, abdominal pain, hepatitis, and hyperbilirubinemia. Diagnosis is through detection of immunoglobulin M antibodies against HAV, and treatment is supportive. Vaccination is the mainstay of prevention and should be given before exposure whenever possible.
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Improvement of mesenchymal stromal cells and their derivatives for treating acute liver failure. J Mol Med (Berl) 2019; 97:1065-1084. [DOI: 10.1007/s00109-019-01804-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 04/28/2019] [Accepted: 05/23/2019] [Indexed: 02/07/2023]
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