Taehan Kan Hakhoe chi = The Korean journal of hepatology最新文献

Background/aims: Impaired glucose tolerance and overt diabetes mellitus (DM) frequently occurs in patients with chronic liver disease. Hyperinsulinaemia and peripheral insulin resistance contribute to the development of DM in these patients. The clinical relevance, however, of DM to their clinical course was not determined. We investigated the prevalence of DM in patients with liver cirrhosis and their clinical characteristics and prognosis.

Methods: A total of 606 consecutive cirrhotic patients were enrolled for 5 years. We reviewed all laboratory findings, clinical courses, and mortality, retrospectively. The cirrhotic patients were divided into two groups according to the presence of DM, and their clinical characteristics and mortality were compared. DM was diagnosed in accordance with National Diabetes Data Group criteria.

Results: Among the total of 606 cirrhotic patients (M:F, 482:124), 346 (57.1%) had HBV related disease and 60 (10%) had HCV related disease. Forty-five percent of the patients had a history of habitual drinking. DM was observed in 22.4% of the cirrhotic patients. In the diabetic group, the frequency of HCV infection was significantly greater. DM did not affect survival. The DM group, however, appeared to have higher mortality in the patients with Child-Pugh class A cirrhosis during long-term follow up. Only 20.6% of the diabetic patients had normal range blood glucose levels even though most of them received medical therapy. The cases with well controlled blood glucose showed higher survival than poorly controlled cases n the DM group.

Conclusions: Cirrhotic patients have a high prevalence of DM, and more frequently are associated with HCV infection. The strict control of blood glucose and the control of infection could be important in prolonging the survival in compensated cirrhotic patients with DM.

Background/aims: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva. The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis.

Methods: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed.

Results: Female gender was dominant in the ratio of 3.4:1. Mean age was 56.4 +/- 2.6. Admission was between 23rd September and 15th November with the peak between mid October and early November. Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6. An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2). Average ALT, AST and GGTP were increased to 93.2 +/- 17.3 IU/L (18 +/- 345 IU/L), 92.5 +/- 11.7 IU/L (34-255 IU/L) and 132.2 +/- 14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal. All the patients improved with doxycycline therapy.

Conclusions: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease.

Background/aims: Screening for hepatocellular carcinoma (HCC) is a common practice in the endemic countries but its exact role has not been fully investigated. The purpose of this study was to determine whether screening can achieve early diagnosis and survival benefits.

Methods: All HCC patients diagnosed at our hospital (September 1994 April 2000) were enrolled; They were divided into two groups; a surveilled group screened with alpha-fetoprotein (AFP) and ultrasound (US) for longer than 6 months before diagnosis and a non-surveilled group. We compared the tumor size, portal vein thrombosis, and stage at initial diagnosis and survival rate between the two groups.

Results: A total of 247 patients were enrolled. 64 were in the surveilled group and 183 were in the non-surveilled group. The tumor size at initial diagnosis in the surveilled group was smaller than in the non-surveilled group (2.6 +/- 2.0 cm vs. 5.7 +/- 4.1 cm, p<0.05). The percentages of patients with stage I, II, III, and IV were 42.2%, 20.3%, 14.1%, 23.4% in the surveilled group and 8.7%, 19.7%, 36.6%, 35.0% in the non-surveilled group. A significantly higher proportion in the surveilled group had earlier stage compared with the non-surveilled group (p<0.05). Portal vein thrombosis in the surveilled group was noticed as significantly less than in the non-surveilled group (9.4% vs. 26.8%, p<0.05). Among Child-Pugh A patients, the cumulative survival rate in the surveilled group was significantly higher than in the non-surveilled group (1 year; 91.4% vs. 70.7%, 2 year; 71.5% vs. 59.9%, p<0.05).

Conclusions: Screening with AFP and US is a useful tool for early diagnosis of HCC, especially with improved survival in Child-Pugh A patients.

Background/aims: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group.

Methods: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients.

Results: 1) The genotype frequencies of ALDH2 (1*1), ADH2 (1*1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1*2) and ALDH2 (2*2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn't find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups.

Conclusions: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.

Background/aims: Lamivudine therapy is effective in inhibiting HBV replications in patients with HBeAg-negative chronic liver disease. However, the sustained response rate appears to be particularly poor, because the vast majority of patients relapse soon after cessation of therapy. The aim of this study was to evaluate the efficacy of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after response in patients with HBeAg-negative chronic liver disease.

Methods: Fifty-nine patients with HBeAg-negative chronic liver disease who have received lamivudine for at least 6 months, were studied. The mean duration of treatment was 14 months. Complete response was defined as undetectable serum HBV DNA by bDNA and normalization of ALT levels. Once HBV DNA disappearance and ALT normalization were observed, lamivudine therapy was continued for at least two additional months. The mean follow-up after cessation of treatment was 6 (1-22) months.

Results: Fifty-six patients were undetectable HBV DNA. The cumulative HBV DNA loss rates at 3 months and 5 months were 90% and 95%, respectively. The ALT normalization was observed in 52 patients. The cumulative ALT normalization rates at 6 months and 10 months were 78% and 86%, respectively. The complete response was observed in 52 patients. The cumulative rates of complete response at 10 months and 18 months were 80% and 88%, respectively. A predictive factor for complete response was only the duration of lamivudine treatment. Virological breakthrough was observed in 5 (8.5%). Thirty-four patients stopped taking lamivudine after 7.7 (2-15) months of the additional therapy. Seventeen of those patients (50%) experienced relapse. The cumulative relapse rates at 3 months, 6 months and 10 months were 24%, 47%, and 66%, respectively. The only predictive factor for relapse was the duration of additional lamivudine treatment after response.

Conclusions: Lamivudine was an effective treatment of HBeAg negative chronic liver disease. Relapse, however, was usually observed after cessation of lamivudine. Our results showed that long-term lamivudine therapy is required in order to decrease the high relapse rates in patients with HBeAg-negative chronic liver disease.

Background/aims: To determine the treatment modalities and the prognosis of a patient with liver cirrhosis, quantitative estimation of liver function is important. We assessed the Child-Pugh score (CPS), the common method as a severity index for the cirrhosis, the Prothrombin, gammaGT, and Apolipoprotein A1 (PGA) index and model for end-stage liver disease (MELD) score. The purpose of this study was to evaluate the correlation between these indices in the patients with cirrhosis only and hepatocellular carcinoma (PHC), according to underlying causes (HBV and alcohol).

Methods: We reviewed medical records of 339 cirrhotic patients with/without hepatocellular carcinoma and divided patient groups by disease and underlying cause: cirrhosis caused by alcohol; LC-Al, cirrhosis caused by HBV; LC-B, hepatocellular carcinoma with cirrhosis caused by alcohol; HCC-Al, hepatocellular carcinoma with cirrhosis caused by HBV; HCC-B. We assessed the CPS, PGA index and MELD score and calculated the correlation coefficient between these scores.

Results: Among the total of 339 patients, 201 patients were diagnosed on the liver cirrhosis only, and 138 patients on the hepatocellular carcinoma with cirrhosis. In each groups, mean score values were not significantly different in CPS, PGA index and MELD score. The correlation of CPS, PGA index and MELD score in all groups, except for the correlation of PGA index and MELD score in HCC-Al group, was significantly positive (p<0.05). Compared to correlation coefficients between three indices, the patients with cirrhosis only had higher tendencies than the patients with hepatocellular carcinoma. The patients by HBV had higher tendencies than by alcohol.

Conclusions: The correlations between CPS, PGA index and MELD score showed significantly positive correlations in the patients with liver cirrhosis only and hepatocellular carcinoma with cirrhosis (except in HCC-Al group). The patients with cirrhosis only had higher correlation coefficients than the patients with PHC and the patients by HBV had higher than by alcohol.

Background/aims: The prognosis of chronic liver disease is closely related to the development of hepatic fibrosis. Liver biopsy is the gold standard method to assess inflammatory activity and fibrosis stage, but this is associated with morbidity and mortality. This study aimed to evaluate the diagnostic value of serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis.

Methods: This study included 100 patients with chronic hepatitis B and cirrhosis. Liver biopsy and histopathologic classification were done. Serum hyaluronic acid and 7S domain of type IV collagen were measured by one step sandwich binding protein assay and radioimmunoassay using polyclonal antibody to 7S domain of type IV collagen, respectively.

Results: The serum concentrations of hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio in the cirrhosis group (139 +/- 98.4 ng/mL, 6.9 +/- 3.5 ng/mL, 1.6 +/- 1.5) were significantly higher (p<0.01) than those in the normal and fatty liver group (20.2 +/- 12.5 ng/mL, 3.5 +/- 0.5 ng/mL, 0.7 +/- 0.3), mild hepatitis group (32.3 +/- 52.7 ng/mL, 3.9 +/- 1.4 ng/mL, 0.7 +/- 0.4), and moderate to severe hepatitis group (68.2 +/- 72.3 ng/mL, 5.3 +/- 2.4 ng/mL, 0.8 +/- 0.4). At the cutoff value of 77 ng/mL for hyaluronic acid and 6.3 ng/mL for 7S domain of type IV collagen and 0.62 for AST/ALT ratio, the sensitivities were 81.8%, 63.6%, 90.9% and specificities were 87.3%, 88.6%, 53.1% for discriminating cirrhosis (fibrosis score: 4) from the mild to severe fibrosis (fibrosis score: 0-3).

Conclusions: Serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio measurement may be clinically useful as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis.

Background/aims: For laboratory diagnostics in liver diseases, many enzymes have been used for the assessment of hepatocellular function. Among them, two transaminases, alanine and aspartate aminotransferase, have been regarded as the most sensitive indicators of hepatocellular damage. However, the enhanced enzyme activities of the enzymes do not exactly indicate or represent the cause and progression of diseases in the patients with liver disease. To overcome such limitations, immunological methods have been suggested as one of the alternatives for the replacement or supplement of the conventional enzymatic analysis.

Methods: In the hope of developing a new assay system for measuring the AST concentration rather than its activity, we have developed a new assay using fluorescence labeled anti-AST monoclonal antibodies. Blood was obtained from a normal population of 234 patients and 43 liver disease patients. The linearity, limit of detection, and performance of the new assay system were tested and evaluated. The comparability of assay was examined with an ELISA and biochemical assays.

Results: The linearity fell in the range of 0-1 mg/L of AST (R=0.995), and the analytical detection limit was 12 microg/L of AST. The mean recovery of the control was 102.4 % in a working range. The precision of the intra- and inter-assay in a range of 50-800 microg/L was CVs < 7% and CVs < 6%, respectively. In the normal population, the mean AST concentration was 35.5 microg/L. The mean AST concentration in patients with liver disease was 266.5 microg/L. The new assay system correlated well with an ELISA and biochemical assay for quantification of AST concentration (R=0.92 and 0.88, respectively; N=43).

Conclusions: We have developed a new immunological assay using generated monoclonal antibodies to human cytosolic AST and used them for the development of a fluorescent assay measuring the enzyme mass. Cytosolic AST mass in sera could be measured reproducibly by the immunological method. In conclusion, this study has provided us with a new type of tool for an accurate measurement of the enzyme amount in circulation.