aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. METHODS: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). RESULTS: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%. CONCLUSIONS: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. LAY SUMMARY: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.

THE ROLE OF VIRAL HEPATITIS IN THE MECHANISM OF LIVER CANCER FORMATION AMONG THE FAR NORTH INDIGENOUS INHABITANTS.

INTRODUCTION: Yakutia is a region of high prevalence of viral hepatitis B, C and D. The rating and ranking of risk factors for the formation of cirrhosis and primary liver cancer in patients with chronic viral hepatitis (CVH) B, C and D in the Republic of Sakha (Yakutia) (R S(Y)), it is a serious medical problem. AIM: Studying of the main reasons for the progression of chronic viral hepatitis B, C and D to cirrhosis and liver cancer in the Far North. MATERIALS AND METHODS: Materials of official statistics of theTerritorial Rospotrebnadzor and official registration of the Ministry of Health of RS (Y); serological and molecular biological research methods to the studying of HCV genotype B, C, D. RESULTS: On the basis of long-term morbidity of chronic viral hepatitis B, C and D and their outcomes in Yakutia defined a role in the progression to cirrhosis and primary liver cancer, ethnicity and genotype of HBV and HDV. Established fact of viral replication in cirrhosis and primary liver cancer under adverse social and environmental factors, genetically determined increased concentration of acetaldehyde due to impaired activity of alcohol dehydrogenases (ADH) and aldegiddegirogenases (AIDG) at the indigenous inhabitants of the republic proves the need for targeted therapy of complex events. CONCLUSIONS: The regions of Yakutia are the most affected by the virus of hepatitis B, C and D with progressive course of the disease to cirrhosis and cirrhosis liver cancer, defined by genotype hepatitis B & D, in which significantly usually occurs primary liver cancer, also noted that the combined mixed-replicating virus hepatitis is a risk factor for primary liver cancer.

THE PREVALENCE OF CHRONIC VIRAL HEPATITIS IN CHILDREN AND ADOLESCENTS IN YAKUTIA.

UNLABELLED: Chronic hepatitis in children represents a serious health and social problem. Under the conditions of the high prevalence of viral hepatitis in Yakutia epidemiological process has a number of peculiarities. In children chronic hepatitis often occurs with minor clinical manifestations, which complicate diagnosis. The study of the epidemiological, clinical and laboratory data is an important task.The aim of the study was to investigate the epidemiological characteristics of chronic hepatitis in children and adolescents living in hyper-endemic region. MATERIALS AND METHODS: The study included 1568 patients'data, registered in the dispensary with a diagnosis of chronic hepatitis in the period from 2000 to 2012. Epidemiological history data of 304 patients with chronic hepatitis were analyzed. The data from official statistics were used for epidemiological analysis. Processing of clinical and laboratory studies was performed using the statistical package IBM SPSS STATISTICS 19. RESULT: CH epidemiological features were identified, including the prevalence of HBV-infection in etiological structure, the high incidence of the disease among the indigenous population, a high risk of intra-familial infection with hepatitis B virus , high frequency of perinatal infection with hepatitis C virus. It was proposed to maximize screening tests for markers of viral hepatitis and to improve quality control of vaccination. CONCLUSIONS: The epidemic process of viral hepatitis in children and adolescents in Yakutia is characterized by domination of HBV-infection in the structure of chronic hepatitis. The predominance of the indigenous nationalities among patients with chronic hepatitis B and the leading role of family contact in the routes structure of infection transmission indicates the importance of ethnic and social factors in contraction of the disease.

High prevalence of reflux esophagitis among upper endoscopies in Chinese patients with chronic liver diseases.

BACKGROUND: Reflux esophagitis (RE) is increasing in prevalence in China. There are very few studies on the prevalence and factors related to RE in patients with chronic liver diseases. The aims of this study were to determine the prevalence of RE by endoscopy in patients with chronic liver diseases and the possible related predictors of RE. METHODS: A total of 1,280 patients with chronic liver disease and 29 patients with acute hepatitis A or E were prospectively evaluated. There were 879 and 401 patients with liver cirrhosis or chronic hepatitis, respectively. RE was classified by endoscopy according to the Los Angeles classification scheme. RESULTS: RE was diagnosed in 36.4% (469/1280) of the chronic liver disease patients, which was significantly higher than in the acute hepatitis patients (10.3% [3/29], P < 0.001). RE accounted for 43.0%, 9.7%, and 60.2% of patients with liver cirrhosis, chronic hepatitis(mild and medium), and liver failure, respectively. A high prevalence of RE existed in patients with liver failure and/or Child B and C liver cirrhosis, with typical symptoms of RE in 21.3% of the patients (100/469). There was a significant relationship between gender, age, ascites, and RE. CONCLUSIONS: The high prevalence of RE among upper endoscopies of patients with severe chronic liver disease was demonstrated. Asymptomatic RE was more common in cirrhotic and liver failure patients. The role of RE in variceal bleeding, however, needs to be demonstrated.

Risk factors for proteinuria in HIV-infected and -uninfected Hispanic drug users.

BACKGROUND: Proteinuria may be an early marker of chronic kidney disease in human immunodeficiency virus (HIV)-infected patients with coexisting chronic hepatitis and/or drug use. Minorities are at greater risk of chronic kidney disease. Data are limited about risk factors for proteinuria in Hispanic drug users with and without HIV infection. STUDY DESIGN: A cross-sectional study. SETTING & PARTICIPANTS: A community-recruited Hispanic cohort to study the role of drug use in HIV-associated malnutrition composed of 4 groups (106 HIV-infected drug users, 96 HIV-uninfected drug users, 38 HIV-infected non-drug users, and 47 healthy controls). Patients on renal replacement therapy were excluded. PREDICTORS: HIV infection, chronic hepatitis, history of hypertension or diabetes, and intravenous drug use (never, prior, or current). OUTCOMES & MEASUREMENTS: The presence of proteinuria was defined as urine dipstick result of 1+ or greater. Multivariable logistic regression was used to identify independent risk factors for proteinuria. RESULTS: Of 287 patients with available data, 24 (8.4%) had proteinuria. In univariate analyses, those with HIV infection; prior, but not current, intravenous drug use; and a history of hypertension or diabetes were more likely to have proteinuria. In multivariate analyses, significant risk factors for proteinuria were HIV infection (odds ratio, 9.2; 95% confidence interval, 1.9 to 45.8; P = 0.007); prior, but not current, intravenous drug use (odds ratio, 4.7; 95% confidence interval, 1.4 to 15.3; P = 0.01); and history of hypertension or diabetes (odds ratio, 8.2; 95% confidence interval, 3.1 to 21.7; P < 0.001). LIMITATIONS: The cross-sectional study design makes it difficult to establish the temporal relationship. The number of outcomes in relation to the number of predictors is small. CONCLUSIONS: HIV and prior intravenous drug use, but not chronic hepatitis or current intravenous drug use, were independently associated with proteinuria in this Hispanic population. Longitudinal studies to assess the development of proteinuria and chronic kidney disease in this high-risk population are warranted.

Prevalence rates of viral hepatitis infections in refugee Kurds from Iraq and Turkey.

BACKGROUND: Since little is known about the burden of viral hepatitis in Kurds, the prevalence of infection with hepatitis A virus (HAV), hepatitis E virus (HEV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was investigated in a sample of refugee Kurds from Iraq and Turkey. PATIENTS AND METHODS: A cross-sectional study was carried out. Serological markers to hepatitis viruses were determined for 1,005 subjects from all age-groups of which 36.6% were from Turkey and 63.4% from Iraq. RESULTS: Overall seroprevalence for anti-HAV was 94.4% and 14.8% for anti-HEV. A significantly higher prevalence for anti-HEV was found among Iraqis (17.5%) compared to Turkish immigrants (10.0%). The prevalence of hepatitis B surface antigen (HBsAg) and total anti-HBc (core) was 6.8% and 35.6% in Turkish Kurds and 2.2% and 12.7% in Iraqis, respectively. Only 10% of children aged up to 10 years and 2.8% of subjects aged 11-20 years had been vaccinated against HBV, the majority of them coming from Iraq. One subject was confirmed as positive for anti-HCV (0.1%) and HCV-RNA and analysis showed a 4c/4d genotype. CONCLUSION: This survey shows a high prevalence of enterically transmitted viral hepatitis in Kurds. HBV infection is moderately endemic, while the prevalence of HCV infection is low. There is a need for a universal immunization strategy for HBV in the Kurd population.

Long-term low dose interferon alpha-2b in the treatment of chronic hepatitis B in multi-ethnic patients in Hawaii.

The antiviral and immunomodulatory effects of interferon were assessed in the treatment of chronic hepatitis B in multi-ethnic patients to prevent viral replication and chronic liver damage. Five million units of recombinant interferon alpha-2b were administered three times a week for 48 weeks to a group of 18 chronic active hepatitis B patients. A complete response was defined as seroconversion to anti-HBe and/or loss of HBe antigen. Seroconversion to anti-HBe in 5 of 12 (42%) chronic active hepatitis B patients occurred after 48 weeks of therapy. HBV-DNA decreased to undetectable levels in 8 of 12 (67%) patients. This chronic low-dose interferon administration regimen demonstrated responses comparable to other studies.

Relationship between intrahepatic expression of hepatitis B viral antigens and histology in Chinese patients with chronic hepatitis B virus infection.

Hepatic cellular and subcellular expression of hepatitis B virus (HBV) antigens--HBsAg, HBcAg, and HBeAg--in 143 Chinese patients with chronic HBV infection were studied by immunohistochemical techniques. Nuclear expression of HBcAg and nuclear and cytoplasmic expression of HBeAg showed a secular trend decreasing from the carrier state and chronic persistent hepatitis (CPH), through chronic active hepatitis (CAH), to cirrhosis with or without hepatocellular carcinoma. In contrast, cytoplasmic HBcAg expression was significantly greater in patients with CPH and CAH (P < .0108). In addition, cytoplasmic HBcAg correlated significantly with lobular activity, portal inflammation, and hepatitic activity (P < or = .007). Expression of cytoplasmic HBcAg also exceeded cytoplasmic HBeAg and nuclear HBcAg in liver specimens showing significant damage (P < .038). HBsAg, however, showed no secular trend and was not related to liver histology. The authors' findings support the theory that HBcAg is also the viral target antigen for immune-mediated liver damage in Chinese patients with chronic HBV infection.

Alpha-fetoprotein glycosylation is abnormal in some hepatocellular carcinoma, including white patients with a normal alpha-fetoprotein concentration.

Lectin-affinity analyses with Lens culinaris agglutinin (LCA) and other lectins have demonstrated that the glycosylation of alpha-fetoprotein (AFP) secreted by hepatocellular carcinomas (HCC) is frequently altered when the serum AFP concentration is increased. To determine if AFP LCA-binding properties are altered in patients with HCC whose serum AFP concentration is normal, the percentage of LCA-binding AFP in serum from white newborns, white normal adults, white patients with chronic hepatitis and hereditary tyrosinemia and white and black patients with HCC were determined. The serum LCA-binding AFP fraction was low in newborns (1-4%) and normal adults (1-8%). There was a significant increase in LCA-binding AFP in patients with chronic hepatitis (10-24%) and hereditary tyrosinemia (5-35%). The AFP LCA-binding fraction was clearly abnormal (greater than 40%) in three of the white patients with an HCC and a normal serum AFP concentration, and the range of values (10-63%) in these HCC patients was similar to that seen in both white and black patients with HCC accompanied by increased AFP concentrations.

HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients.

To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4 were significantly more frequent in patients with autoimmune hepatitis than in controls. HLA-DR4 was most frequently associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of Dw between the patients and the controls who were DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.

Antibodies to hepatitis C virus in autoimmune liver disease: evidence for geographical heterogeneity.

To resolve conflicting reports about the occurrence of antibodies against hepatitis C virus (HCV) in patients with autoimmune chronic active hepatitis (AI-CAH), sera from UK and Italian patients were tested with the original anti-HCV assay (Ortho) and a novel anti-HCV assay (UBI) based entirely on synthetic HCV peptides. 28 (60%) of 47 Italian patients with type-1 AI-CAH were anti-HCV-positive by Ortho ELISA, 25 of whom were also strongly positive by the UBI assay. 15 (60%) of 25 UK patients with type-1 AI-CAH were HCV-positive by Ortho ELISA but only 2 were positive by the UBI assay. Similarly, 29 (88%) of 33 Italian patients with type-2 AI-CAH, but 0 of 10 UK patients, were very strongly anti-HCV-positive with the UBI assay. Italian patients with AI-CAH appear to have a high frequency of genuine exposure to HCV, whereas seropositivity by the Ortho HCV ELISA in UK patients is likely to represent a false-positive result. These findings indicate important geographical and/or genetic influences in autoimmune liver disease among different populations.

[HLA and disease in Argentina. Serologic and genomic polymorphism]. / HLA y enfermedad en la Argentina. Polimorfismo serológico y genómico.

In this report we discuss the results of the association of chronic active hepatitis (B virus) and coeliac disease with HLA class I and class II antigens, in patients of Latin American Caucasian origin. Evidence is presented showing that the alleles involved differ from those reported in other Caucasian populations of different ethnic background. Differences were observed both at the serology and at the DNA (RFLP) level. The relevance of these findings regarding the clinical implications as well as the molecular mechanisms involved in the associations are discussed.

Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis.

Eleven patients of Chinese origin experienced spontaneous reactivation of chronic active hepatitis B. Eight HBsAg-positive patients were followed for an average of 15 months prior to, while three others presented during reactivation. Fatigue, hepatomegaly and jaundice were frequent findings. Elevation of both serum ALT (average = 1,212 units per liter) and hepatitis B virus DNA levels were noted in all patients, and reactivation lasted an average of 4.4 months. During resolution, clinical symptoms abated, serum ALT levels reverted toward normal, and in nine patients, the hepatitis B virus DNA values became undetectable. All patients lacked evidence for acute hepatitis A, Epstein-Barr Virus, cytomegalovirus or hepatitis delta virus infection. Histologic findings of liver tissue from eight patients showed piecemeal necrosis and fibrosis. Within the parenchyma, varying degrees of hepatocytolysis with cuffing, perivenular necrosis and acidophilic bodies were noted. Ground-glass cells and regenerative changes also were observed. Cirrhosis was not present in any of the liver biopsies. These findings suggest that spontaneous reactivation of hepatitis B occurs in heterosexual patients with chronic active hepatitis B and contributes to chronic inflammation and to the progression of their liver disease.

Hepatitis delta virus infection: a recently imported disease in New Zealand.

In a study of 565 hepatitis B antigen (HBsAg) positive persons from the Auckland region, antibody to the hepatitis delta virus was detected in 38. The largest number were in Samoans (61%) although the infection was present in some other Pacific Islanders. Among HBsAg positive healthy blood donors, antenatal patients and acute hepatitis patients between 3.8 and 4.8% were anti-delta positive; while 28% of chronic hepatitis patients were positive suggesting an association between this disease and delta infection. Some positive results were also found in sera from intravenous drug addicts. By contrast, anti-delta was uncommon in New Zealand born Maoris or Europeans. Delta infection can be detected in some Pacific Islanders, some European immigrants as well as intravenous drug addicts and has the potential to spread in an epidemic form to HBsAg carriers in the general community. Widespread vaccination against hepatitis B is recommended to eventually reduce the number of HBsAg carriers in New Zealand.