Kentaro Yoshioka

Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis B virus infection for the fiscal year 2008 in Japan

In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35u2003years and those aged 35 years or older. Even for patients with chronic hepatitis who are negative for hepatitis e antigen (HBeAg), but who harbor HBV DNA in titers of 7u2003log copies/mL or more, a “drug‐free state” is aimed for by sequential treatment with interferon (IFN) plus entecavir as the first line. For patients with chronic hepatitis B aged 35u2003years or older, who are HBeAg‐negative and carry HBV DNA in titers of less than 7u2003log copies/mL, long‐term IFN for 24–48u2003weeks is adopted anew. To HBeAg‐negative patients who have either or both platelet counts of less than 150u2003×u2003103/mm3 and less than 7u2003log copies of HBV DNA, also, long‐term IFN for 24–48u2003weeks is indicated.

Liver stiffness measured by transient elastography correlates with fibrosis area in liver biopsy in patients with chronic hepatitis C

Aim:u2002 Liver stiffness (LS) measured by transient elastography (TE) has been reported to correlate with liver fibrosis, which is usually semiquantitatively assessed. In the present study, the fibrosis area was measured by image analysis software in liver biopsy specimens and its correlation with LS was assessed.

Efficacy of peginterferon-α-2b plus ribavirin in patients aged 65 years and older with chronic hepatitis C.

Objectives: The aim of this study was to evaluate the efficacy and indication of combination therapy with ribavirin plus peginterferon‐α‐2b in chronic hepatitis C virus (HCV) patients aged 65 years and older.

Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C

Aim:u2002 To assess the regression of liver fibrosis after interferon (IFN) treatment in patients with chronic hepatitis C, liver stiffness (LS) was measured repeatedly and the factors associated with reduction of LS were assessed.

Reduction of liver stiffness by antiviral therapy in chronic hepatitis B

BackgroundLiver stiffness (LS) has been reported to correlate with fibrosis stage (F). The correlation between LS and fibrosis stage and the reduction of LS by antiviral therapy were examined in patients with hepatitis B infection.MethodsLS was measured by FibroScan in 212 patients infected with hepatitis B virus. Liver biopsies were done in 51 patients. Changes of LS were assessed in 29 patients treated with nucleotide or nucleoside analogs and 52 patients without antiviral therapy.ResultsLS was significantly correlated with fibrosis stage (ρxa0=xa00.686, Pxa0<xa00.0001). The optimal cut-off values of LS were 7.1xa0kPa for Fxa0≥xa02, 10.7xa0kPa for Fxa0≥xa03, and 16.0xa0kPa for F4. LS was significantly reduced by antiviral therapy, from 12.9 (range 6.2–17.9) kPa to 6.6 (4.4–10.3) kPa measured at an interval of 512 (range 366–728) days (Pxa0<xa00.0001). Eleven of 19 (58%) patients with baseline fibrosis stages of F3-4 deduced from LS had 2-point or greater reductions of deduced stage at the last LS measurement. The change ratio of hyaluronic acid (Pxa0=xa00.0390) was associated with a 2-point or greater reduction of deduced fibrosis stage. Without antiviral therapy, LS tended to increase, increasing from 6.1 (range 3.9–8.5) kPa to 6.3 (range 4.4–9.7) kPa at an interval of 422 (range 358–709) days (Pxa0=xa00.0682).ConclusionsLS was significantly correlated with fibrosis stage in patients with chronic hepatitis B. The reduction of LS by antiviral therapy was significantly correlated with the reduction of hyaluronic acid. Thus, we conclude that LS can be useful to assess the progression and regression of liver fibrosis stage noninvasively.

Transient elastography: Applications and limitations

Transient elastgraphy with use of FibroScan is one of most accurate methods for assessment of liver fibrosis. FibroScan can be readily used with an operator with a short training. In many different studies, liver stiffness measured by transient elastgraphy correlates well with fibrosis stages, and cutoff values of liver stiffness for fibrosis staging are similar even among different diseases. However there is wide variation of stiffness values in the same fibrosis stage, and some overlap between the adjacent stages. In addition, inflammatory activity and size of nodule of cirrhosis affect the liver stiffness values. The reproducibility may be reduced by age, obesity, steatosis, narrow intercostal space and lower degrees of hepatic fibrosis in patients. Thus the estimation of fibrosis stages from liver stiffness should be cautiously done. To improve the accuracy of liver fibrosis staging, the combination of transient elastography with other noninvasive methods such as FibroTest should be required.

Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders

BackgroundIron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes.MethodsWe measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography–tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis.ResultsOne patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes.ConclusionDetermining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.

Efficacy of ribavirin plus interferon-α in patients aged ≥60 years with chronic hepatitis C

Background:u2002 In Japan, patients with hepatitis C virus (HCV)‐associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of combination therapy in such patients.

Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated‐interferon‐alpha 2b and ribavirin combination therapy

Summary.u2002 Mutations in two regions of hepatitis C virus (HCV) have been implicated in influencing response to interferon (IFN) therapy. Substitutions in the NS5A region of HCV have been associated with response to IFN therapy, and this region has been known as the IFN sensitivity‐determining region (ISDR). The mutations in the core region of HCV have also been reported to predict IFN response. The aim of this study was to investigate whether amino acid substitutions in the core region and ISDR among patients with HCV genotype 1b affect the response to IFN therapy. A total of 213 patients who completed IFN treatment were randomly selected. All patients received pegylated‐IFN‐alpha 2b once each week, plus oral ribavirin daily for 48u2003weeks. Of the 213 patients, 117 (54.9%) showed early virologic response (EVR), with HCV‐negativity, at 12u2003weeks. Factors related to EVR on multivariate analysis were non‐Gln70 and Leu91 in the core region, and ISDR mutant‐type. One hundred and two (47.9%) showed a sustained virologic response (SVR). SVR occurred more frequently in patients without Gln70 (55.4%) than in those with Gln70 (21.3%) (Pu2003<u20030.0001). SVR was achieved in 43.6% of patients with wild‐type ISDR and 62.5% of patients with mutant‐type (Pu2003=u20030.0227). Of the 34 patients who simultaneously had non‐Gln70 and mutant‐type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on multivariate analysis were non‐Gln70 and ISDR mutant‐type. In conclusion, amino acid substitutions in the core region and ISDR were useful for predicting the response to IFN in patients with HCV genotype 1b.

Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy

Background and aims: Mutations in the core and NS5A region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. Genome‐wide association studies have revealed that the single‐nucleotide polymorphism (SNP) of interleukin 28B (IL28B) contributes to IFN response. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the core and NS5A region affect the response to IFN therapy.