Global epidemiology of hcv infection

The prevalence of hepatitis C virus (HCV) infection is estimated to be 3% worldwide. Regional variation is related to differences in risk factors, health care practices, economic issues, and societal norms. In recent years, blood screening programs and improved public awareness have led to a reduction in new cases of HCV in western countries. Despite these advances, new infections continue to occur, particularly in the developing world. An understanding of the global epidemiology of HCV provides the basis for generating public health initiatives to address this growing problem.     

The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers

The presence of antibodies to HTLV-III and markers of active hepatitis B virus replication was examined in a longitudinal study of 33 consecutive male homosexual HBsAg carriers. The mean follow-up time was 37 months (range = 4 to 109 months). All patients were initially hepatitis B virus DNA-positive and HBeAg positive. Antibodies to HTLV-III were detectable in eight patients while they were positive for both of these markers. One of them cleared hepatitis B virus DNA and seroconverted from HBeAg to anti-HBe. This corresponds to an annual clearance/seroconversion rate of 4% (95% confidence limits = 0 to 15%). In two patients, antibodies to HTLV-III appeared after clearance of hepatitis B virus DNA and HBeAg, and in one of them, hepatitis B virus DNA reappeared. Among the 25 patients negative for HTLV-III antibodies, the annual hepatitis B virus DNA clearance rate was 20% and HBeAg to anti-HBe seroconversion rate was 11% (95% confidence limits = 11 to 31% and 4 to 20% respectively). The observed hepatitis B virus DNA clearance rates in the two groups were significantly different (p less than 0.05). Disease activity, as determined by transaminase levels, was significantly lower in HTLV-III-infected individuals as compared to individuals without HTLV-III infection (p less than 0.05). Infection with HTLV-III may extend the period of active viral replication or even reactivate hepatitis B virus replication and seems to diminish inflammatory disease activity in chronic HBsAg carriers.     

The natural history of chronic HBV infection

Chronic hepatitis B (CHB) is a disease of worldwide importance that carries considerable morbidity and mortality. The natural course of CHB is characterized by an initial hepatitis B e antigen (HBeAg)-positive phase marked by immunologic tolerance, high-level viremia, and histologic quiescence, followed by an immune elimination phase of variable duration that is associated with less viremia but increased disease activity, usually resulting in HBeAg clearance. The ensuing HBeAg-negative phase is characterized by even lower or undetectable viremia with biochemical and histologic quiescence. This inactive carrier state may be of short or lifelong duration and occasionally results in hepatitis B surface antigen clearance. Alternatively, the HBeAg-negative phase may demonstrate intermittent or continuous disease activity, resulting in progressive liver fibrosis, leading to cirrhosis and portal hypertension. Compensated or decompensated cirrhosis is associated with considerable mortality due to complications of portal hypertension and, most importantly, with the development of hepatocellular carcinoma, which is frequent in patients with CHB.     

The natural history of hepatitis C viral infection

Although early data suggested that chronic hepatitis C virus infection carried little risk, studies with longer duration of infection have reported concerning results. Of patients with acute infection, approximately 80% will develop chronic infection. The greatest risk of morbidity comes with cirrhosis and the resulting increased risk of hepatocellular carcinoma. The true risk of progression to cirrhosis, however, has emerged as an area of controversy. Both host and viral factors seem to impact susceptibility to chronic infection, cirrhosis, and hepatocellular carcinoma. Hepatitis C virus has become the most common indication for liver transplantation, but the infection routinely recurs and may have a more aggressive course after transplantation. Given that current treatment options for hepatitis C virus infection are clearly not optimal, informed decisions regarding treatment require an in depth understanding of the natural history.     

The natural history of human immunodeficiency virus infection

Although much is known about the natural history of HIV infection, many issues remain unresolved and require additional study. At least four major questions require further investigation. (1) Current data suggest that most HIV-infected persons will eventually develop AIDS. The proportion of all infected persons who will eventually develop AIDS, as well as the average and maximum incubation periods, have not yet been conclusively defined. (2) Certain clinical signs (such as oral candidiasis) or laboratory test results (such as a depressed T4 count) may indicate a poorer prognosis. However, the predictive value of such indicators for a specific patient and in an individual situation varies. Combinations of clinical and laboratory data may help refine estimates of the likelihood of developing AIDS or other HIV-related diseases. (3) Why some HIV-infected persons develop disease and others do not is not completely understood. The role of cofactors for disease progression needs additional investigation. There may be no one universal cofactor for progression but, rather, various agents that cause immune stimulation and reactivation of latent HIV. Therefore, exposure to a variety of infectious or environmental agents (such as through sexually transmitted diseases or injection of iv drugs) may accelerate progression to disease in HIV-infected persons. (4) It is not established whether antiviral agents will prevent or reduce the likelihood of disease progression in asymptomatic HIV-infected persons. If beneficial, should they be given to all HIV-infected persons or only to those whose clinical and laboratory evaluation suggests an increased likelihood of progression? Given these uncertainties, how should the physician or other health care worker evaluate, treat, and counsel the HIV-infected patient? Such patients should receive a comprehensive medical evaluation for both diagnostic and staging purposes; the details of such an evaluation are beyond the scope of this review and have been well described. A few brief points, however, should be emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)     

The natural history of chronic hepatitis C virus infection

In conclusion, the natural history of chronic HCV infection has not yet been fully defined. Current data suggest that the process runs an indolent course during the first two decades after initial infection, accounting for modest morbidity and mortality. Serious sequelae are more likely to emerge as the disease process enters the third and fourth decades after infection. These sequelae will presumably be concentrated among those whose liver biopsies display features of cirrhosis, but seem less likely to effect those with liver biopsy evidence of chronic hepatitis alone unless their disease advances to cirrhosis. The frequency of progression from chronic hepatitis to cirrhosis as the disease process enters the third decade remains to be determined. Associated chronic alcoholism appears to be an important additive factor, but other factors that might promote disease progression need to be defined. It seems probable that end-stage liver disease will result in only a proportion of infected individuals. If so, the challenge is to learn how to determine for each individual during the course of their chronic illness what outcome can be expected.     

The natural history of hepatitis C virus infection.

The natural history of HCV infection remains ill-defined. The knowledge accumulated on the progression of HCV to date is important, however. It is now abundantly clear that the progression of disease is generally slow, and the development of cirrhosis and its complications is a possibility, not a probability as hitherto thought. Predicting the outcome remains a quandary for clinicians. Ultimately it will be possible to define the natural history of hepatitis C infection through a combination of research in the fields of virology, immunology, and molecular biology and by monitoring the biochemical and histologic progress of the disease. Only then will it be possible to intervene appropriately and develop new therapies to prevent the progression to cirrhosis and hepatocellular carcinoma.     

The natural history of chronic hepatitis B virus infection

Three stages of chronic hepatitis B virus (HBV) infection are recognized: the immune tolerant phase, the chronic hepatitis B phase, and the inactive hepatitis B carrier phase. Active liver disease is most often found in persons with elevated aminotransferase levels and HBV DNA levels >10(5) copies/mL. Possible risk factors for developing liver disease include older age, male gender, presence of hepatitis B e antigen (HBeAg), HBV genotype, mutations in the precore and core promoter regions of the viral genome, and coinfection with hepatitis D (delta) virus. All persons chronically infected with HBV should be followed every 6 to 12 months with aminotransferase levels. Those with elevated levels should be tested for HBeAg and its antibody (anti-HBe) as well as HBV DNA levels to determine if they are in need of further evaluation with a liver biopsy and are candidates for antiviral therapy. Future research will help clarify the outcome of chronic HBV infection.     

The impact of hepatic steatosis on the natural history of chronic hepatitis C infection

Summary.  Since patients with hepatitis C virus (HCV) often have hepatic steatosis, this retrospective analysis aimed to assess whether steatosis influences fibrosis progression. We studied 112 HCV RNA positive subjects (median age 44, IQR 39–51 years), who had two liver biopsies performed (median biopsy interval 50, 34–74 months). Fibrosis was staged using the Ishak method and steatosis by the Kleiner system (<5% steatosis = S0, 5–33% = S1, 33–66% = S2, and >66% = S3). The subjects were untreated because they had mild fibrosis ( n =  59), declined therapy ( n =  48), or had co-existing disease precluding treatment ( n  =   5). On first liver biopsy, 60 (54%) had S0, 34 (30%) had S1, 12 (11%) had S2, and 6 (5%) had S3. Steatosis was associated with genotype 3, odds ratio 4.8 (95% CI 1.3–16.7, P =  0.02). Twenty-three patients (21%) had disease progression on the second biopsy, defined as an increase in Ishak score by ≥1 stage. On univariate analysis, fibrosis progression was associated with older age ( P =  0.004), higher AST ( P =  0.04), and steatosis ( P =  0.005) but on multivariate analysis, only baseline steatosis was significant, odds ratio 14.3 (2.1–111.1, P =  0.006). Kaplan-Meier analysis demonstrated that steatosis impacted on time to progression to both significant fibrosis (Ishak ≥F3) and cirrhosis (Ishak F5-6) ( P =  0.001 and P =  0.049, respectively). The finding that steatosis was significantly associated with fibrosis progression indicates that, independent of baseline fibrosis stage, patients should be considered for anti-viral treatment if steatosis is present. Furthermore, strategies to reduce steatosis may have a beneficial effect on fibrosis progression and, therefore, patient outcome.     

Some aspects of the natural history of HIV infection

Studying factors influencing the length of the incubation period of HIV/AIDS is important to our understanding of the natural history of the disease and for the decision when to start with anti-retroviral therapy. In a multicentre study among HIV-positive homosexual men with a known date of seroconversion, we found that the median survival time after HIV infection was 12.1 years. Age is an important determinant of the survival: the older the shorter the incubation period and survival. Gender does not seem to play a role, but women appear to have higher CD4 counts than men at seroconversion, AIDS and death. HIV-positive drug users often die before they 'reach' AIDS often from HIV-related causes e.g. bacterial infections. In a multicentre study we found that such pre-AIDS mortality is now also found among homosexual men and haemophiliacs but at a much lower level. Most studies show that HIV subtype does not influence the incubation period. On the other hand genetic factors do play an important role.     

The influence of host factors on the natural history of chronic hepatitis C viral infections

The natural history of hepatitis C is variable, with some patients progressing rapidly to cirrhosis and others showing no significant fibrosis over many decades. A number of studies have examined the factors that influence disease progression. Age at time of infection, gender, alcohol abuse and, perhaps, route of transmission, appear to have the greatest influence on the natural history of the hepatitis C virus with the possible exception of alcohol, the mechanism whereby these factors influence disease progression has yet to be determined.     

The changing epidemiology and natural history of hepatitis C virus infection

Injection drug use remains the predominant mode of transmission of hepatitis C virus (HCV) infection. Growing numbers of persons who have been chronically infected with HCV for 20 or more years are coming to medical attention and are at risk for serious complications of chronic infection, including cirrhosis and hepatocellular carcinoma. Factors linked with the development of advanced fibrosis and cirrhosis include age at infection, duration of infection, heavy alcohol use, coinfections with HIV or hepatitis B virus, and male sex. Emerging risk factors for disease progression include steatosis, insulin resistance (and factors associated with the metabolic syndrome), and host genetics.     

Influence of extrahepatic viral infection on the natural history of hepatitis C

HCV is primarily hepatotropic, but there is mounting evidence pointing to infection and replication of extrahepatic sites. Here we evaluated the occurrence of HCV infection of peripheral blood mononuclear cells (PBMC) and explored the possible association between viral extrahepatic infection and the natural history of the disease. Forty seven Chilean, HCV infected, treatment naïve patients were included in the study. HCV RNA was isolated from plasma and PBMC and subsequently reverse transcribed, amplified and sequenced. Most patients harbored HCV 1b genotype and the most common route of infection showed to be blood transfusion. HCV RNA was readily detected in PBMCs of 34 out of the 47 patients (72%). We report that HCV sequences found in PBMC differ from those in plasma of the same subjects strongly suggesting HCV compartmentalization. In addition, we found that patients with detectable HCV RNA in PBMC had a tendency for being more likely cirrhotic [OR 3.8 (95% CI: 0.98 to 14)]. In conclusion, this study provides further arguments for the existence of HCV infection of extrahepatic sites and suggests that extrahepatic infection could be a factor influencing the natural history of the disease.     

The natural history of portal hypertensive gastropathy: influence of variceal eradication

OBJECTIVE: The natural history and likelihood of bleeding from portal hypertensive gastropathy (PHG) present in patients with portal hypertension before endoscopic variceal obliteration may differ from that in patients who develop PHG during or after variceal eradication. METHODS: A total of 967 variceal bleeders who had achieved variceal eradication by endoscopic sclerotherapy in the recent past were prospectively studied. In all, 88 (9.1%) patients (cirrhosis in 54, noncirrhotic portal fibrosis in 18, and extrahepatic portal vein obstruction in 16) had distinct mucosal lesions. PHG alone was present in 78, PHG with gastric antral vascular ectasia (GAVE) in eight, and GAVE alone in two patients. PHG was graded as mild or severe and according to whether present before (group A) or after endoscopic intervention (group B). Patients underwent regular endoscopy at follow-up to see if the PHG was transitory (disappearing within 3 months), persistent (no change), or progressive. Bleeding from PHG lesions was defined as acute or chronic. RESULTS: Twenty-two (26%) patients had PHG before (group A) and 64 (74%) developed PHG after variceal eradication (group B). During a mean follow-up of 25.1 +/- 14.2 months, PHG lesions disappeared in group A in only two patients (9%), but in group B in 28 (44%) patients (p < 0.05). PHG lesions more often progressed in the former as compared to the latter (18% vs 9.4%, p = NS). The incidence of bleeding was higher in group A than group B (32% vs 4.7%, p < 0.02). Bleeding from PHG occurred in 10 patients (11.6%); seven of them were from group A, and all had either progressive (n = 3) or persistent (n = 4) lesions. CONCLUSIONS: PHG developing after variceal eradication is often transitory and less severe. If PHG is pre-existing, endoscopic therapy for varices could worsen the PHG, with a likelihood of bleeding. Such patients may be benefited by concomitant beta-blocker therapy.     

HBV感染自然史研究进展

病毒复制与宿主免疫之间的动态平衡在HBV感染自然史进展和发病机制中起重要作用。多数免疫能力正常的成人感染HBV后呈自限性,而在婴幼儿则多发展成为慢性HBV感染。慢性HBV感染分为4期：免疫耐受期、HBeAg阳性慢性肝炎期、非复制的HBsAg携带期和HBeAg阴性慢性肝炎期。HBVDNA水平、HBeAg的状态以及ALT水平可以预测HBV感染的长期结局如肝硬化或肝细胞癌。本文对HBV感染自然史分期、慢性HBV感染的结局和预后进行了综述。