HBsAg-Negative, Anti-HBc–Negative Patients Still Have a Risk of Hepatitis B Virus–Related Hepatitis after Autologous Stem Cell Transplantation for Multiple Myeloma or Malignant Lymphoma

박현성,김도영,김수정,정혜림,조현수,장지은,정준원,민유홍,송재우,김진석 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose Although hepatitis B surface antigen (HBsAg)–negative, hepatitis B core antibody (anti-HBc)– negative patients are not considered to be at risk for hepatitis B virus (HBV)–related hepatitis, the actual risk remains to be elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in HBsAg-negative, anti-HBc–negative patients receiving autologous stem cell transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma. Materials and Methods We retrospectively reviewed data from 271 HBsAg-negative patients (161 anti-HBc–negative and 110 anti-HBc–positive at the time of ASCT) who received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed according to the presence of anti-HBc. HBV serology results at the time of ASCT were compared with those at the time of diagnosis of MM or lymphoma. Results Three patients (two anti-HBc–negative MMs and one anti-HBc–positive MM) developed HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not differ among patients with or without anti-HBc status (p=0.843). HBV-related hepatitis more frequently occurred in MM patients than in lymphoma patients (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who were HBsAg–negative and anti-HBc–positive at the time of diagnosis had lost anti-HBc positivity during chemotherapy prior to ASCT. Conclusion Our data suggest that HBsAg-negative, anti-HBc–negative patients at the time of ASCT for MM or lymphoma still might be at a risk for HBV-related hepatitis.

Comparing the Clinical Features and Outcomes of Acute Hepatitis E Viral Infections with Those of Acute Hepatitis A, B, and C Infections in Korea

( Hye Won Oh ),( Ra Ri Cha ),( Sang Soo Lee ),( Chang Min Lee ),( Wan Soo Kim ),( Hyun Chin Cho ),( Jin Joo Kim ),( Jae Min Lee ),( Hong Jun Kim ),( Chang Yoon Ha ),( Hyun Jin Kim ),( Tae Hyo Kim ),( 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Genotype 3/4 hepatitis E virus (HEV) is an emerging infection in developed countries. This study investigated the etiology of acute viral hepatitis, and compared the clinical features of HEV infections with those of hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in Korea. Methods: This study included 116 consecutive patients who were diagnosed with acute viral hepatitis between January 2007 and January 2016. Acute viral infections were observed in 23 patients with HEV (19.8%), 49 patients with HAV (42.2%), 28 patients with HBV (24.1%), and 16 patients with HCV (13.8%). Results: The incidence of acute HEV infection was higher among older patients (median age: 49 years) and male patients (69.6%), and was associated with the consumption of undercooked or uncooked meat 43.5%). Most acute HEV infections were associated with pre-existing liver disease (e.g., alcoholic liver disease, chronic hepatitis B, biliary stones, and autoimmune hepatitis) and frequently presented with jaundice (56.5%). HEV-infected patients exhibited significantly lower median peak alanine aminotransferase levels (525 U/L), compared to HAV-infected patients (2,413 U/L, P < 0.001) and HBV-infected patients (1,356 U/L, P = 0.001). HEV-infected patients exhibited significantly higher median total bilirubin levels (6.8 mg/dL), compared to HCV-infected patients (1.2 mg/dL, P = 0.028). Two HEV-infected patients were diagnosed with Guillain-Barre syndrome, although no patients developed fulminant hepatitis. Conclusions: Our findings indicate that HEV is no longer a rare cause of acute viral hepatitis in Korea.

HBV : PE-028 ; Prevalence of hepatitis A, B, C and D viruses among patients with acute hepatitis in Mongolia

( O. Baatarkhuu ),( Do Young Kim ),( B Bayarmagna ),( N Khorolsuren Baigal ),( R Ouyngerel ),( D Enkhsaikhan ),( Y Dahgwahdorj ),( Sang Hoon Ahn ),( Kwang Hyub Han ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background and Aims: Mongolia is an endemic area of acute and chronic viral hepatitis. To determine the prevalence of HAV, HBV, HCV and HDV infections among patients with acute hepatitis in Mongolia during outbreaks. Methods: A total of 624 patients (353 males and 271 females; age, 18.6±8.1 years; range 2-66 years) who were clinically diagnosed with acute hepatitis during outbreak from October 2011 to March 2012 in Ulaanbaatar, Mongolia have been studied. The prevalence of hepatitis virus infections was determined by testing of serum for the IgM class of antibodies against HAV, HBV, HCV, HDV, and HBsAg. Results: Acute hepatitis A (AHA) (IgM anti-HAV positive) was diagnosed in 284 patients (45.5%). Acute hepatitis B (AHB) (IgM anti-HBc positive) was diagnosed in 191 patients (30.6%) and 22 patients (3.5%) was diagnosed as co-infection of B and D. Acute hepatitis C (AHC) (IgM anti-HCV positive) was diagnosed in 33 patients (5.3%). There were 52 (8.3%) HBV carriers who had detectable HBsAg and anti-HDV but who were negative for both IgM anti-HAV and IgM anti-HBc, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. Forty-two (6.5%) patients were found to be infected by various combinations of dual viruses such as HAV/HBV (2.8%), HAV/HDV (0.6%), HBV/HCV (2.5%), and HCV/HDV (0.6%). AHA was the most prevalent in subjects aged 1-19 years, AHB and HBV+HDV superinfection were the first and second most prevalent in the age group of 20-29 years, and AHC was the most common type in 40-49 years. Conclusion: Dual hepatitis viral infection was detected in approximately 6.5% among patients with acute hepatitis in Mongolia.

만성B형 간염 환자에서 발생한 A형 간염에 의한 다발성 장기부전 1예

윤한결,김나영,김자선,이기종,연재우,백소야,박영민 대한내과학회 2011 대한내과학회지 Vol.80 No.-

Hepatitis A virus is a major cause of viral hepatitis worldwide. The prevalence of hepatitis A in young adults has recently been increasing in Korea. Hepatitis A infection rarely complicates fulminant hepatitis, acute pancreatitis, and acute renal failure. We experienced a case of multiple organ failure involving fulminant hepatitis, acute pancreatitis, and acute renal failure complicating a hepatitis A superinfection in a chronic hepatitis B patient. The patient was a 38yearold man who presented with febrile sense and myalgia. He was initially alert, but became confused and developed acute renal failure and acute pancreatitis. He received continuous renal replacement therapy and conservative treatment and completely recovered from the multiple organ failure. It is important to consider a variety of potential complications in hepatitis A patients, especially in those with underlying chronic liver disease. (Korean J Med 2011;80:S111-S116) A형 간염 바이러스는 세계적으로 바이러스성 간염의 주요한 원인이다. 최근 우리나라에서는 젊은 성인에서의 A형 간염이 증가하고 있다. A형 간염은 드물게 전격성 간염, 급성 췌장염, 급성 신부전을 일으킨다. 저자들은 만성 B형 간염 환자가 A형 간염 바이러스 중복감염에 의해 전격성 간염, 급성 췌장염, 급성 신부전의 다발성 장기 부전을 보인 증례를 경험하였다. 38세 남자 환자가 열감, 근육통이 있어 내원하였다. 초기에 의식이 명료하였으나 의식이 혼탁해지고 급성 신부전, 급성 췌장염이 발생하였다. 환자는 지속적 신대체 요법과 보존적 치료를 받았으며, 다발성 장기 부전에서 완전히 호전되었다. 특히 기저 간 질환이 있는 환자에서 A형 간염의 여러 합병증에 대한 주의를 기울여야 할 것으로 생각된다.

Original Article : Factors influencing the severity of acute viral hepatitis A

( Joo Il Kim ),( Yun Soo Kim ),( Young Kul Jung ),( Oh Sang Kwon ),( Yeon Suk Kim ),( Yang Suh Ku ),( Duck Joo Choi ),( Ju Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3

Background/Aims: Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods: We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results: The incidence of fulminant hepatitis was 1.4 % (10/713) in patients with acute hepatitis A. Thirty-three (4.6 %) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions: While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection. (Korean J Hepatol 2010;16:295-300)

HBV : PE-028 ; Prevalence of hepatitis A, B, C and D viruses among patients with acute hepatitis in Mongolia

( O Baatarkhuu ),( Do Young Kim ),( B Bayarmagnai ),( N Khorolsuren ),( B Baigal ),( R Ouyngerel ),( D Enkhsaikhan ),( Y Dahgwahdorj ),( Sang Hoon Ahn ),( Kwang Hyub Han ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background and Aims: Mongolia is an endemic area of acute and chronic viral hepatitis. To determine the prevalence of HAV, HBV, HCV and HDV infections among patients with acute hepatitis in Mongolia during outbreaks. Methods: A total of 624 patients (353 males and 271 females; age, 18.6±8.1 years; range 2-66 years) who were clinically diagnosed with acute hepatitis during outbreak from October 2011 to March 2012 in Ulaanbaatar, Mongolia have been studied. The prevalence of hepatitis virus infections was determined by testing of serum for the IgM class of antibodies against HAV, HBV, HCV, HDV, and HBsAg. Results: Acute hepatitis A (AHA) (IgM anti-HAV positive) was diagnosed in 284 patients (45.5%). Acute hepatitis B (AHB) (IgM anti-HBc positive) was diagnosed in 191 patients (30.6%) and 22 patients (3.5%) was diagnosed as co-infection of B and D. Acute hepatitis C (AHC) (IgM anti-HCV positive) was diagnosed in 33 patients (5.3%). There were 52 (8.3%) HBV carriers who had detectable HBsAg and anti-HDV but who were negative for both IgM anti-HAV and IgM anti-HBc, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. Forty-two (6.5%) patients were found to be infected by various combinations of dual viruses such as HAV/HBV (2.8%), HAV/HDV (0.6%), HBV/HCV (2.5%), and HCV/HDV (0.6%). AHA was the most prevalent in subjects aged 1-19 years, AHB and HBV+HDV superinfection were the first and second most prevalent in the age group of 20-29 years, and AHC was the most common type in 40-49 years. Conclusion: Dual hepatitis viral infection was detected in approximately 6.5% among patients with acute hepatitis in Mongolia.

바이러스간염의 예방과 예방접종

송병철 ( Byung Cheol Song ),조유경 ( Yoo Kyung Cho ) 대한내과학회 2012 대한내과학회지 Vol.82 No.2

Hepatitis viruses are most important cause of acute and chronic hepatitis. In past, hepatitis B virus was one of the major causes of acute hepatitis. Recently, around 60-70% of acute hepatitis is attributed to hepatitis A virus infection. In this article, we will discuss the route of hepatitis virus infection, how to prevent transmission of viral hepatitis and who should be immunized to each hepatitis viruses. (Korean J Med 2012;82:123-133)

Current and future strategies for the treatment of chronic hepatitis C

( Omar Alshuwaykh ),( Paul Y. Kwo ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

Chronic hepatitis C infection is a major cause of liver disease and hepatocellular carcinoma worldwide. While hepatitis C has been treated for decades with some success, the introduction of direct acting antiviral agents has revolutionized the treatment of hepatitis C with finite, highly effective, well-tolerated therapy and there are few populations that cannot be successfully treated now or are complicated to manage. The World Health Organization has released elimination targets in an effort to eliminate viral hepatitis and reduce dramatically the morbidity and mortality caused by both viral hepatitis. While hepatitis C is straightforward to treat, it remains problematic to eliminate on a global scale. Diagnosis of hepatitis C remains the major gap in the cascade of care and numerous screening strategies will be required to reduce this gap. While historically, treatment of hepatitis C has been centralized, decentralized approaches will be required to diagnose, evaluate, and link to care the large population of individuals worldwide with hepatitis C across low-, middle-, and high-income countries. With the introduction of multiple pangenotypic treatment options and reduced cost for these therapies, assessment and treatment for those with hepatitis C has been simplified and made more accessible worldwide. There are multiple populations for whom care models are being developed and refined, including those when inject drugs, those who are incarcerated, those who present with sexually transmitted disease including the men who have sex with men population, amongst many others. While a vaccine for hepatitis C remains elusive these efforts continue. Multiple successful elimination efforts have been reported. (Clin Mol Hepatol 2021;27:246-256)

HCV, Acute, LT : Expression of PD-1 and CTLA-4 is Increased during Symptomatic Phase of Acute Hepatitis A

( Chang Wook Kim ),( Hyo Sun Cho ),( Hee Yeon Kim ),( Sung Won Lee ),( Jeong Won Jang ),( Jong Young Choi ),( Seung Kew Yoon ),( Young Sok Lee ),( Chang Don Lee ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Inhibitory molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with antiviral effector T-cell dysfunction, which influences on T-cell exhaustion and persistent viral infection. These PD-1 and CTLA-4 are up-regulated in chronic viral infection such as chronic hepatitis C, chronic hepatitis B and human immunodeficiency virus infection but there is no report about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A. We investigated the expression of PD-1 and CTLA-4 during symptomatic and convalescent phases of acute hepatitis A. Methods: Seven patients with symptomatic acute hepatitis A, 5 patients with non-viral acute toxic hepatitis were enrolled for detection of PD-1 and CTLA-4 on T-cell subset of peripheral blood mononuclear cells (PBMC) isolated from these subjects during symptomatic and convalescent phases by flow cytometry. Five as healthy control were also examined for comparison with these patients. Results: Symptomatic acute hepatitis A showed significant increase of PD-1 and CTLA-4 expression compared to non-viral acute toxic hepatitis or healthy control (PD-1; 18.3±15.7% vs. 3.7±3.0% vs. 1.6±1.8%, P<0.05, CTLA-4; 23.5±12.0% vs. 6.1±1.2% vs. 5.9±1.2%, P<0.05)(median±SD). In addition, highly expressed PD-1 and CTLA-4 were dramatically decreased in convalescent phase of acute hepatitis A. Conclusions: In acute hepatitis A, PD-1 and CTLA-4 are upregulated during symptomatic phase then down-regulated after recovery. This changing pattern of PD-1 and CTLA-4 expression was not seen in non-viral acute toxic hepatitis. Our findings suggest that PD-1 and CTLA-4 have protective effect as inhibitory molecules to suppress cytotoxic T-cells which induce destruction of viral infected hepatocytes in acute hepatitis A.

Isolation of hepatitis E virus genotype 4 from patients with acute cryptogenic hepatitis in Korea

Jeong, Sook-Hyang,Park, Byung-Joo,Kim, Yong-Hyun,Choi, Yun Suk,Ahn, Hee-Seop,Han, Sang-Hoon,Choi, In-Soo Elsevier 2017 Journal of clinical virology Vol.89 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Autochthonous hepatitis E occurs sporadically in developed countries. The consumption of undercooked pork containing hepatitis E virus genotype 3 (HEV-3) or 4 (HEV-4) is the major risk factor for infection. The serological diagnostic kits currently used in hospitals sometimes produce false-negative or −positive results. Therefore, detection of both HEV RNA and antibodies to the virus is required for confirmative diagnosis of hepatitis E.</P> <P><B>Objectives</B></P> <P>We aimed to detect HEV in serum samples from patients with cryptogenic hepatitis and to determine the origin of HEV.</P> <P><B>Study design</B></P> <P>A nested polymerase chain reaction (PCR) method was developed for detection of HEV-3 and HEV-4 in patients with hepatitis. A total of 23 serum samples, deposited in 2006–2012, from patients with acute cryptogenic hepatitis who were serologically negative for hepatitis A, B, C, and E were examined using this method. The amplified PCR products were genetically analyzed.</P> <P><B>Results</B></P> <P>Four HEV-4 isolates were detected from the 23 serum samples. Phylogenetic analysis indicated that three of the four isolates were closely related to HEV-4 isolates found in pigs in Korea and in patients with hepatitis E in Japan.</P> <P><B>Conclusions</B></P> <P>The newly developed nested PCR method was useful for detection of HEV in patients with cryptogenic hepatitis. The close relationship between the human HEV-4 isolates identified in this study and swine isolates implied that zoonotic transmission of HEV might be a source of infection in patients with hepatitis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A nested PCR method was developed for detection of HEV-3 and HEV-4. </LI> <LI> HEV-4 isolates were identified in serum of patients with cryptogenic hepatitis. </LI> <LI> These isolates were closely related to swine and Japanese HEV-4 strains. </LI> </UL> </P>