Opportunistic infection in patients with acute liver failure

Background

Treatment with systemic corticosteroids is often used for acute liver failure (ALF), but this has increased the number of profoundly immunocompromised patients and cases of opportunistic infection.

Methods

Between January 2007 and December 2012, all patients (n = 51) referred to the Chiba University Hospital for treatment of ALF were studied. Patients with prothrombin activity of 40 % or less of the standardized values were defined as having ALF. Patient age, sex, cause of ALF, alanine aminotransferase and total bilirubin levels, prothrombin activity and total amount of corticosteroid were analyzed to determine the factors associated with the occurrence of opportunistic infection.

Results

Opportunistic infections occurred in 21.6 % (n = 11) of ALF patients. Thirty-five patients underwent systemic corticosteroid therapy, and 31.4 % of those patients showed opportunistic infections. Cytomegalovirus (n = 9, 81.8 %) and Pneumocystis jiroveci (n = 6, 54.5 %) were the microorganisms frequently suspected as the causes of opportunistic infection. In 7 (63.6 %) of the 11 cases of opportunistic infection, 2 or more species of microorganism were detected. Seven patients (63.6 %) with opportunistic infection were cured by treatment. Cox regression analysis for the patients who underwent systemic corticosteroid therapy steroid treatment revealed that age over 52 years (compared to younger patients: odds ratio = 9.62, 95 % confidence interval = 1.22–76.9) was only the predictive factor for the occurrence of opportunistic infection.

Conclusion

Opportunistic infections are not rare in ALF patients, and the appropriate diagnosis and treatment of these infections are critical during ALF treatment.     

Hepatitis C virus infection in the United States

Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States, and most infected persons are younger than 50 years old. The relative importance of the two most common exposures associated with transmission of HCV, blood transfusion and intravenous drug use (IVDU), has changed over time. Blood transfusion, which accounted for a substantial proportion of HCV infections acquired >10 years ago, rarely accounts for recently acquired infections. In contrast, IVDU has consistently accounted for a substantial proportion of HCV infections and currently accounts for 60% of HCV transmission while sexual exposures account for up to 20%. Other known exposures (occupational, hemodialysis, household, perinatal) together account for about 10% of infections. In the remaining 10%, no recognized source of infection can be identified, although most persons in this category are associated with low socioeconomic level. Case-control studies have found no association with military service or exposures resulting from medical, surgical or dental procedures, tattooing, acupuncture, ear piercing or foreign travel. Reducing the burden of HCV infection and disease in the United States requires implementation of primary prevention activities that reduce or eliminate HCV transmission and secondary prevention activities that reduce liver and other chronic diseases in HCV-infected persons by identifying them and providing appropriate medical management and antiviral therapy. Surveillance and evaluation activities also are important to determine the effectiveness of these programs in reducing the incidence of disease, identifying persons infected with HCV, and promoting healthy lifestyles and behaviors.     

Hepatitis B virus infection in patients with idiopathic liver disease

We studied 67 HBsAg-negative Israeli patients (36 negative for all HBV serological markers as group 1 and 31 positive for antibodies to HBs and HBc as group 2) with chronic liver disease and cirrhosis of unknown origin using a rapid, sensitive and specific assay for the detection of low levels of hepatitis B virus in serum. This technique uses a high-affinity monoclonal antibody to HBs against an a domain epitope of HBsAg to capture the virion, followed by hepatitis B virus DNA amplification with the polymerase chain reaction. In addition, 55 subjects without liver disease served as controls: Group 3 (n = 32) was negative for all hepatitis B virus markers; group 4 (n = 23) was positive for antibodies to HBs and HBc. We found 11 individuals in group 1 (31%) and 10 in group 2 (29%) harboring low levels of hepatitis B virus DNA in serum. In contrast, no one in group 3 or group 4 was positive by this technique (p less than 0.0001). Using polymerase chain reaction primers spanning other regions of the hepatitis B virus genome and a method of restriction-fragment analysis of polymerase chain reaction-amplified sequences, we detected significant DNA sequence heterogeneity, suggesting infection with distinct hepatitis B virus strains. DNA extracted from paraffin-embedded liver biopsy specimens of 42 patients from groups 1 and 2 was shown to contain hepatitis B virus DNA by polymerase chain reaction in 11 of 12 patients with circulating virion DNA. More important, 18 additional patients whose sera were negative by HBs-antibody capture/polymerase chain reaction amplification had hepatitis B virus DNA sequences in their livers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatitis C virus infection in patients with acute hepatitis B

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied using a second-generation ELISA test in 121 patients with self-limiting acute hepatitis B, including 63 intravenous drug addicts (IVDA). Within the first month after the onset of illness, 47.1% of the patients were anti-HCV positive, this figure reaching 52.1% six months later. The prevalence in the sixth month was significantly higher in the IVDA (93.6%) than in the non-IVDA (6.9%) (p < 0.00001). Among the IVDA, anti-HCV was more frequent in those with (100%) than in those without hepatitis delta virus (HDV) coinfection (84.6%) (p = 0.004). Of the 63 anti-HCV positive patients, 36 (57.1%) continued to exhibit abnormal transaminase levels for more than six months, while this was not observed in anti-HCV negative patients. These results show a high prevalence of infection by hepatitis C virus (HCV) in IVDA with acute B hepatitis. As a rule, infection by HCV occurred prior to the hepatitis B infection, although occasionally simultaneous infections were observed. HCV appears to be the agent responsible for chronic liver disease in patients with acute B hepatitis who become HBsAg negative.     

Acute liver failure in the United States

In the last 5 years the use of a multicenter approach has helped to define acute liver failure (ALF) in the United States. Drug-related hepatotoxicity comprises more than 50% of cases of ALF, including acetaminophen toxicity (40%) and idiosyncratic drugs (approximately 12%). Nearly 20% of cases remain of unknown etiology. Outcome of ALF is determined by etiology; by the degree of hepatic encephalopathy present on admission; and by complications, principally infection. More than 43% survive without a transplant, 28% die, and 29% undergo liver transplantation. Liver support machines have had no impact on this condition to date. A trial of N-acetylcysteine for the treatment of ALF not related to acetaminophen toxicity is underway. Future research in ALF in the United States should focus on limiting the number of cases related to drugs, searching for causes of the indeterminate cases, and developing more effective temporary liver support.     

Analysis the predisposing factors and clinical prognosis of Hepatitis B patients with acute on chronic liver failure

目的 分析乙型肝炎并发慢加急性肝衰竭(ACLF)的发病诱因、临床特征及其临床预后的影响因素,探讨影响慢性乙型肝炎肝衰竭患者预后的危险因素.方法 将260例乙型肝炎并发慢加急性肝衰竭患者分为治愈好转组和无效病死组,并对其发病诱因、临床特征及其临床预后的影响因素进行分析.结果 260例乙型慢加急性肝衰竭患者,治愈好转组109例,好转率为41.92％,无效病死组151例,总死亡率为58.08％;年龄和性别对病死率无明显影响.慢加急性肝衰竭最主要的诱因依次为HBV活动及变异(51.53％)、非病毒性感染(23.08％)、消化道出血(11.10％)和其他(14.29％);两组患者血清生化指标中凝血酶原活动度、低钠血症比较差异有统计学意义(P＜0.01).结论 乙型肝炎并发慢加急性肝衰竭的临床过程复杂,其预后与诱因、并发症以及反映病情程度的生化指标等改变明显相关.     

Hepatitis B immunity in United States military recruits

BACKGROUND: In 2002, the US Department of Defense (DoD) mandated hepatitis B immunization for military recruits. A DoD study reported that screening for immunity with selective immunization would be cost-effective at a prevalence of immunity of >12%. The prevalence of hepatitis B immunity in the military recruit population was unknown. METHODS: We studied a random sample of Army, Navy, and Marine Corps new recruits (2400 men and women from all 50 states, Puerto Rico, and US territories). Banked serum samples collected in 2001 were tested for antibody to hepatitis B surface antigen (anti-HBs) by AUSAB enzyme-linked immunoassay (EIA). Results were evaluated by military service branch, age, sex, race, level of education, geographic region of origin, and presence of state immunization laws. RESULTS: The overall prevalence of anti-HBs seropositivity, adjusted to the age distribution of the recruit population in 2001, was 31.5% (95% confidence interval [CI], 29.6%-33.4%). The prevalence of anti-HBs seropositivity, directly adjusted to the 18-35-year-old US population in 2000, was 23.0% (95% CI, 20.7%-25.3%). Anti-HBs seropositivity prevalence was highest among the young, decreased with increasing age, and was higher in women, recruits from the Northeast and West, and recruits from states with laws mandating hepatitis B immunization before entry into elementary and middle school. CONCLUSIONS: Screening new recruits for evidence of immunity before hepatitis B immunization is indicated. The prevalence of immunity increased with successive birth cohorts and may reflect the success of childhood immunization programs.     

慢加急性乙型肝炎肝衰竭患者发生感染和急性肾损伤危险因素分析

目的 探讨慢加急性乙型肝炎肝衰竭(HBV-ACLF)患者发生感染和急性肾损伤(AKI)的危险因素.方法 2017年9月～2019年9月我科收治的HBV-ACLF患者102例,发生感染48例,发生AKI 32例,应用Logistics回归分析影响患者并发感染和AKI的相关影响因素.结果 感染组住院天数≥15 d、存在侵入...     

Hepatitis C virus infection in United States correctional institutions

In the United States, over 6 million people are under correctional supervision and over 2 million are in custody and receiving health care. Prisoners are overrepresented by individuals with high risk for hepatitis C virus (HCV) infection, including injection drug users, the sexual partners of injection drug users, and people living with HIV or AIDS and mental illness. As such, it is estimated that approximately 30% of all prisoners are infected with HCV. Despite this high prevalence, little has been done to implement effective therapy for treating this potentially curable infection in this setting. Correctional settings, with their structured environment and managed care approach, are ideal settings to screen, evaluate, and provide treatment and promote risk reduction interventions that will contribute to society’s improved public health.     

Hepatitis type C virus infection in patients with type B chronic liver disease

Anti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAgpositive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.     

Hepatitis B virus infection and liver function in patients with systemic lupus erythematosus

One hundred patients with systemic lupus erythematosus (SLE) were investigated for serological markers of hepatitis B virus (HBV) and had liver function evaluated. One patient had hepatitis B surface antigen and 25 had antibodies to HBsAg which is not significantly different from normal blood donor controls. Minor liver function abnormalities were found in 35 patients and there was no difference between those with and without anti-HBs. A single patient without HBV markers had more severe liver enzyme elevation. Our data do not show a relationship between SLE and HBV and support the contention that liver diseases in lupus is mild.     

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.     

Hepatitis type C virus infection in patients with type B chronic liver disease.

Anti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAg-positive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.     

Hepatitis B virus infection among household contacts of patients with acute HBsAg-positive hepatitis

Summary Sixty-seven household contacts of 31 index cases with acute HBsAg-positive hepatitis were investigated forHepatitis B virus (HBV) markers. Follow-up findings in 50 household contacts revealed that six spouses and/or sexual partners had developed acute clinical hepatitis B. Three of these six contacts were drug addicts. A further seven contacts showed serological changes compatible with exposure to HBV, but had no signs of acute clinical hepatitis. Six of these seven contacts were spouses and/or sexual partners of their index case. Possible prophylactic or post-exposure measures only seem to be necessary in the spouses and/or sexual partners of patients with acute hepatitis B.

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Hepatitis-B-Virus-Infektion bei Personen mit Familienkontakt zu Patienten mit akuter HBsAg-positiver Hepatitis

Zusammenfassung Siebenundsechzig Personen, die in häuslichem Milieu Kontakt zu 31 Fällen mit akuter HBsAg-positiver Hepatitis hatten, wurden auf Hepatitis-B-Virus (HBV) Marker untersucht. In Verlaufskontrollen bei 50 Personen mit Kontakt zu den Hepatitis-Kranken zeigte sich, daß sechs Ehegatten und/oder Geschlechtspartner eine klinisch akute Hepatitis B entwickelt hatten. Weitere sieben Kontaktpersonen wiesen serologische Veränderungen auf, die mit einer Exposition gegenüber HBV vereinbar waren; doch hatten diese Personen keine klinisch manifeste Hepatitis. Sechs dieser sieben Kontaktpersonen waren Ehegatten und/oder Geschlechtspartner des jeweiligen Hepatitisfalles. Prophylaktische oder therapeutische Maßnahmen nach Exposition scheinen nur bei Ehegatten und/oder Geschlechtspartnern von Patienten mit akuter B-Hepatitis erforderlich zu sein.

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Other members of the group:P. Christoffersen, O. Dietrichson, V. Faber, C. Gluud, G. Høybye, K. Iversen, E. Juhl, P. Kryger, L. R. Mathiesen, P. Petersen, H. Poulsen, P. Schlichting, P. Skinhøj, T. I. A. Sørensen.