Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients.

BACKGROUND & AIMS: Genotypes and viremia of hepatitis D virus (HDV) and hepatitis B virus (HBV) may be associated with outcomes. This study evaluated the impact of viral genotypes and viremia on outcomes of dual HBV and HDV infection. METHODS: Viremia and viral genotypes were analyzed in 194 consecutive chronic hepatitis B patients with HDV superinfection and correlated with outcomes. RESULTS: The numbers of HBV genotype A, B, C, and nonclassified were 4, 57, 23, and 110, respectively. There were 51 genotype I HDV, 74 genotype II HDV, 8 genotype IV HDV, and 61 nonclassified HDV genotype. In a median follow-up of 135 months, 24 progressed to cirrhosis and 41 developed hepatocellular carcinoma. Patients infected with genotype I HDV had a lower remission rate (15.2% vs 40.2%; P = .007) and more adverse outcomes (cirrhosis, hepatocellular carcinoma, or mortality) (52.2% vs 25.0%; P= .005) than those with genotype II HDV. Patients infected with genotype C HBV had a lower remission rate (0 vs 32.1%; P = .005) and more adverse outcomes (70.0% vs 33.9%; P = .005) than those with genotype B HBV. The presence of HBV or HDV viremia was associated with lower remission rates compared with those negative for both (26.4% and 24.3% vs 69.2%; P < .001). In multivariate analysis, age, genotype C HBV, and genotype I HDV were independent factors associated with adverse outcomes. CONCLUSIONS: In chronic HBV and HDV dual infections, older age, genotype I HDV, and genotype C HBV correlated with adverse outcomes.

[Biliary tract in patients with chronic viral hepatitides].

AIM: To characterize motor-kinetic and inflammatory changes in extrahepatic biliary tracts and gallbladder in patients with chronic viral hepatitis (CVH). To ascertain whether there is a pathogenetic correlation between affection of the biliary system and viral infection. MATERIAL AND METHODS: The condition of the biliary tract was examined in 183 patients with CVH using fractionated duodenal tubing with biochemical tests and bacteriological investigation of bile, dynamic ultrasonic investigation. RESULTS: 69.9% patients were diagnosed to have dysfunction of the Oddi's sphyncter caused by its hypertonicity, 4.4% patients had hypotonic sphyncter. Hyper- and hypotonicity of the gallbladder were observed in 45.8 and 20.8% patients, respectively. Biliary dysfunction was associated with the process activity but not with a nosological form of the disease. Chronic acalculous cholecystitis was verified in 21.2% patients. CONCLUSION: Chronic HBV and HCV infections are accompanied with biliary dysfunctions associated with activity of inflammation in the liver. Oddi's sphincter dysfunction in CVH is a risk factor of gallbladder inflammation.

[Apoptosis of peripheral blood lymphocytes in patients with chronic viral hepatitis]. / Apoptoz limfotsytiv peryferychnoï krovi u khvorykh na khronichnyi virusnyi gepatyt.

The examined 68 patients with chronic viral hepatitis (CVH) demonstrated a high Fas/APO-1 (CD95) expression on the peripheral blood lymphocytes. It correlated with the serum level of the tumor necrosis factor alpha (TNF alpha). The above findings suggest to us the implication of apoptosis in CVH pathogenesis. Following administration of interferonotherapy treatments the number of lymphocytes in the presence of apoptosis has gotten decreased.

Changing pattern of chronic hepatitis D in Southern Europe.

BACKGROUND & AIMS: The aim of this study was to assess changes in the clinical pattern of hepatitis D virus (HDV) infection in Italy, brought about by improved control of hepatitis B and D viruses, and to establish the natural history of chronic hepatitis D. METHODS: Histological diagnosis and clinical features of 122 patients with HDV recruited from 1987 to 1996 in three Italian tertiary referral centers (Torino, northern Italy; San Giovanni Rotondo and Castellana Grotte, southern Italy) were compared with those of 162 patients collected in the same centers in the previous decade. Patients from both groups with at least 6 months of follow-up were included in a new subgroup to assess the natural history of the disease. RESULTS: Among 162 patients referred from 1977 to 1986, 9 (6%) had mild hepatitis at histology vs. 9 (8%) of 122 patients referred in the second decade; 105 (65%) vs. 21 (17%) had severe hepatitis; 46 (28%) vs. 38 (31%) had histological asymptomatic cirrhosis; and 2 (1%) vs. 54 (44%) had clinically overt cirrhosis. For 159 patients (121 men and 38 women; mean age, 34 +/- 11), a follow-up of more than 6 months was documented, and they were included in the natural history subgroup. After 78 +/- 59 months of follow-up, 112 (70%) survived free of liver transplantation: 9 underwent transplantation, 32 died of liver failure, and 6 of acquired immunodeficiency syndrome. Estimated 5- and 10-year probability of survival free of orthotopic liver transplantation was 100% and 100% for patients with mild hepatitis, 90% and 90% for severe hepatitis, 81% and 58% for histological asymptomatic cirrhosis, and 49% and 40% for clinical cirrhosis (P < 0.01), respectively. CONCLUSIONS: Occurrence of fresh and severe forms of hepatitis D has diminished greatly in Italy. Contemporary patients represent cohorts infected years ago who survived the immediate medical impact of hepatitis D. The disease has been asymptomatic and nonprogressive in a minority; in the majority, it rapidly advanced to cirrhosis but thereafter subsided with stable clinical conditions for more than a decade.

Natural history of chronic viral hepatitis in childhood.

Chronic Hepatitis B virus (HBV) infection in children is commonly associated with Hepatitis B e antigen (HBeAg) seropositivity and histologic features of minimal to moderate hepatitis. Remission of liver disease is the rule following HBeAg to antiHBe seroconversion and clearance of HBV DNA from serum. In intermediate and low endemicity areas chronic HBV infection is usually acquired postnatally, and more than 80% of children are likely to achieve stable remission during the pediatric age. Severe sequelae, namely cirrhosis and HCC, have been observed only in less than 4% of children followed over two decades. In all cases cirrhosis was an early complication. Chronic HCV infection is usually silent in children. The chronicity rate seems to be high (50-80%) in post-transfusion hepatitis C as well as in perinatally acquired infection. HCV-associated liver disease is characterized by fluctuations of ALT which remain below two times the normal in about half of the cases. Liver histology shows minimal to mild hepatitis in the large majority of patients and cirrhosis is rare. Few patients achieve spontaneous remission and progression to a more severe liver disease might occur in adult life.

Viral induction of autoimmunity: mechanisms and examples in hepatology.

Autoimmunity may be observed in chronic viral hepatitis, in particular hepatitis C and D. The hepatitis C virus (HCV) displays numerous interactions with the immune system. Hepatitis C virus induces a number of diseases of presumed autoimmune background, like mixed cryoglobulinaemia, glomerulonephritis, panarthritis, arthritis, thyroiditis and skin lesions. On the other hand a number of autoantibodies are observed during the course of hepatitis C. Of particular interest are liver/kidney microsomal antibodies (LKM). Their occurrence in viral hepatitis may indicate an increased risk for treatment with interferons. LKM antibodies in chronic hepatitis C recognize several autoepitopes differing from those in autoimmune hepatitis. Hepatitis C-associated LKM antibodies are more heterogeneous. They recognize either conformational or several distinct linear autoepitopes on cytochrome P450 2D6; they may also react with other microsomal proteins. Apart from their molecular weight at 59 and 70 kDa these microsomal antigens are not yet identified. Another model of virus-induced autoimmunity in man is chronic hepatitis D which always requires co-infection with hepatitis B. Hepatitis D is known to be associated with a number of autoantibodies, amongst them LKM-3. LKM-3 antibodies have recently been shown to react with proteins of the UDP glucuronosyltransferase family (UGT). The main antigen is an autoepitope expressed on exon 2-5 of family 1 UGTs. Some hepatitis D sera recognize a minor second epitope on family 2 UGTs. It is interesting that hepatitis C patients recognize proteins of the cytochrome P450 family while hepatitis D sera react with UGTs. There seems to be little overlap between autoimmunity seen in hepatitis C and D as far as autoepitopes are concerned. LKM-3 antibodies against UGT 1 are also seen in a minority of patients with autoimmune hepatitis type 2. However, the autoimmune response against UGTs seen in autoimmune hepatitis differs from that observed in viral hepatitis. Autoantibodies in autoimmune liver disease are usually more homogenous and are directed against precise linear epitopes. Autoepitopes in autoimmune hepatitis usually represent conserved regions of these proteins, the antibody usually is inhibitory and antibody titres are very high. In contrast, autoantibodies in viral hepatitis are more heterogenous, recognize several linear and conformational epitopes; antibody titres are much lower. However, the major LKM autoantigen in chronic hepatitis C also is P450 2D6. Autoimmune hepatitis and autoimmunity in viral hepatitis must be distinguished clinically by all means due to the need for specific therapeutic interventions. These liver diseases may serve as models to study virus induced autoimmunity and autoimmune disease in man.