Summary. The pathogenesis of thrombocytopenia in chronic hepatitis is not well known. This study evaluated the relationship between liver injury, serum thrombopoietin, splenomegaly and thrombocytopenia in chronic viral hepatitis. Two hundred and nine patients were enrolled, 85 with splenomegaly and 124 without. Thrombocytopenia was present in 71% and 23% of patients with or without splenomegaly respectively. In subjects with low platelet count, those with splenomegaly showed significantly lower platelet numbers than those without splenomegaly. The spleen size correlated with portal hypertension. An inverse correlation between spleen size and platelet count was observed (r 20´54; P , 0´0001). In patients without splenomegaly, thrombocytopenia was associated with the grade of fibrosis; platelet counts were the highest in patients with fibrosis 0±2, lower in those with grade 3 (P , 0´008) and lowest in those with grade 4 (P , 0´05). These findings were independent of demographic and biochemical characteristics, hepatic necroinflammatory activity, portal hypertension and splenomegaly. Patients with normal platelet counts showed higher thrombopoietin levels than those with low platelet counts (P , 0´0001). An inverse correlation between thrombopoietin levels and fibrosis grade was observed (r 2 0´50; P , 0´0001). Median thrombopoietin levels were 58 and 27 pg/ml for fibrosis grade 0±1 and grade 4 respectively (P , 0´001). These data indicate that advanced hepatic fibrosis, causing an altered production of thrombopoietin and portal hypertension, plays the central role in the pathogenesis of thrombocytopenia in chronic viral hepatitis.

The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r ‫؍‬ 0.367; P ‫؍‬ .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 mol/L, respectively (P ‫؍‬ .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P ‫؍‬ .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR ‫؍‬ 7.1), HAI (OR ‫؍‬ 3.8), liver fibrosis (OR ‫؍‬ 4.0), and HCV genotype 3 (OR ‫؍‬ 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P ‫؍‬ .03), HAI (P ‫؍‬ .0001), and steatosis (P ‫؍‬ .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC. ( H epatic steatosis frequently occurs in hepatitis C virus (HCV) infection, more so than in subjects with hepatitis B virus. 1 The prevalence of fatty infiltration in the livers of chronic hepatitis C (CHC) has been reported to average around 50%, with a range of 30% to 70%. 2-4 For HCV genotype 3 infection, it has been suggested that the virus exerts a direct steatogenic effect, supported by correlation of steatosis with the levels of HCV RNA, and by the reversal of steatosis as the result of antiviral therapy. [5][6][7][8] Moreover, the degree of steatosis has been related to the extent of hepatic fibrosis in CHC. 5,[9][10][11][12] The mechanisms involved in HCV-associated steatosis are unknown. Several host (body mass index [BMI], insulin resistance, hypertrigliceridemia) and viral factors may be implicated. Among viral factors, at least two HCV proteins-core and NS5A-have been credited with the ability to alter lipid metabolism in infected cells, thus causing hepatic steatosis in the absence of immune response. 13,14 In the transgenic mouse model, it has also been shown that the HCV core protein induces steatosis. 15 Transgenic mice expressing HCV co...

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Summary Background : Drug‐resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. Aim : To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. Methods : Eight anti‐hepatitis B e‐positive patients with (group A) and 14 patients without clinical exacerbation (five anti‐hepatitis B e‐positive, group B1; nine hepatitis B e antigen‐positive, group B2) during lamivudine treatment were investigated. Results : ‘Polymerase region’: M204V/I variants were found in all group A patients, but in none of group B1 (P = 0.0007) and in four of nine of group B2 (44%; P = 0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. ‘Core promoter’: the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P = 0.03) of group B1 and one of nine (11%; P = 0.002) of group B2 patients. ‘Precore’: the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P = 0.004) of group B1 and one of nine (11%; P = 0.002) of group B2. Conclusions : Different mutational patterns were observed in the lamivudine‐treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation.