Dar-In Tai

A one year trial of Lamivudine for chronic hepatitis B

BACKGROUND AND METHODSnIn preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score.nnnRESULTSnHepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of lamivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100-mg dose of lamivudine was associated with a reduced progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events.nnnCONCLUSIONSnIn a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.

Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis: A prospective study

A prospective surveillance of hepatocellular carcinoma (HCC) using serum alpha-fetoprotein and high-resolution, linear-array, real-time ultrasonography was carried out in 432 patients with clinicopathologically proven chronic type B hepatitis. During a follow-up period of 6-85 mo (median 23, mean 26.9 +/- 16.8 mo), asymptomatic HCC was identified in 8 patients, with a calculated annual incidence of 826/100,000, and 2768/100,000 for patients over age 35 yr. The relative risk of developing HCC in hepatitis B surface antigen-positive chronic hepatitis patients was 2 when compared to those that were hepatitis B surface antigen-negative, and was 5 when compared in patients over age 35 yr. Hepatocellular carcinomas detected by these methods were in a relatively early stage as most tumors were small, only 50% were associated with cirrhosis, 37.5% were positive for hepatitis B e antibody, and most were still resectable. We, therefore, recommend a combination of alpha-fetoprotein and ultrasonography surveillance in patients with chronic hepatitis in order to improve the chance of early HCC detection as well as the chance for successful resection. In addition, the low incidence of cirrhosis and hepatitis B e antibody in these patients with early HCCs and the occurrence of hepatitis B e antigen/hepatitis B e antibody seroconversion after HCC had developed suggest that the development of HCC and progression from hepatitis to cirrhosis were two independent (though related) sequelae of chronic hepatitis B virus infection.

Hepatic decompensation associated with hepatitis B e antigen clearance in chronic type B hepatitis

To examine hepatic decompensation associated with acute exacerbation preceding hepatitis B e antigen clearance in chronic type B hepatitis, 376 patients with chronic hepatitis who were hepatitis B e antigen-positive were prospectively studied for up to 7 yr (mean 25 mo). Among the 165 patients who underwent hepatitis B e antigen clearance, 4 patients experienced hepatic decompensation and one of them eventually developed hepatic encephalopathy and died. The incidence of hepatic decompensation associated with hepatitis B e antigen clearance was 2.4%. We suggest that such an event in previously unrecognized chronic hepatitis B carriers could have been erroneously interpreted as acute or subacute hepatic failure, and that it might have been the result of a stronger enhancement of the host immune response.

Long-term outcome of hepatitis B e antigen–negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time†

The baseline alanine aminotransferase (ALT) level was reported to have prognostic value in chronic hepatitis B virus (HBV) infection, during which ALT may change over time. Instead of baseline ALT, this study aimed to study the prognostic value of the height of ALT during the course of chronic HBV infection. A total of 4376 asymptomatic hepatitis B e antigen (HBeAg) negative, surface antigen (HBsAg) carriers with baseline ALT less than 2 times the upper limit of normal (ULN) were monitored with ALT measurement and ultrasonography every 3 to 12 month for over 3 years. Maximal ALT levels during follow‐up were correlated with long‐term outcomes using morbidity and mortality data from hospital records, cancer registration, and national mortality database. Baseline ALT level was normal in 3673 subjects and increased to abnormal level in 1720 (46.8%) during a mean follow‐up period of 13.4 ± 5.2 (3.0‐28.7) years. The incidence of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality increased with increasing maximal ALT level during follow‐up, especially in those with maximal ALT of at least 2 times ULN, as compared with those who maintained normal ALT. Cox regression analysis indicated that age at entry, sex, and maximal ALT level during follow‐up were significant independent factors associated with the development of cirrhosis, HCC, and mortality whereas cirrhosis was also an independent factor for HCC development and mortality. Conclusion: Persistently normal ALT was associated with excellent long‐term prognosis, whereas increasing ALT levels of at least 2 times ULN during follow‐up was associated with increasing morbidity and mortality. ALT of at least 2 times ULN is therefore an appropriate threshold for anti‐HBV therapy, whereas those with ALT 1 to 2 times ULN require liver biopsy for decision. (HEPATOLOGY 2009.)

Role of Helicobacter pylori in cirrhotic patients with peptic ulcer. A serological study.

Helicobacter pylori was found to be a promoter factor of peptic ulcer that has an incidence higher in patients with hepatic cirrhosis. To clarify the role betweenH. pylori and peptic ulcer in patients with hepatic cirrhosis, a serological test (ELISA test, HEL-p, AMRAD, Australia), was used to measure the presence ofH. pylori of patients with hepatic cirrhosis. Within two years, 108 cirrhotic patients who had received a panendoscopic examination were enrolled in this study. There were 79 males and 27 females with a mean age of 53.2 years. Sixty-four cases had positive serum HBsAg and 44 had negative serum. The results showed that the prevalence ofHelicobacter pylori in cirrhosis was 43.5% (47/108). There was no difference of HEL-p-positive rate between peptic ulcer and normal gastroduodenal mucosa (45.2% vs 46.1%,P>0.05). According to this study, there appears to be no relation between peptic ulcer andH. pylori in patients with hepatic cirrhosis. The etiology of peptic ulcer in cirrhotic patients need further study.

Hepatitis C virus infection facilitates gallstone formation.

Background:u2002 Bile duct damage and hepatic steatosis are two characteristic histological findings in hepatitis C virus infection; and high prevalence of hepatitis C antibody is noted in patients with cholangiocarcinoma. The purpose of the present study was to examine the relationship between biliary diseases and hepatitis C virus infection.

AFP-L3 in Chronic Liver Diseases with Persistent Elevation of Alpha-fetoprotein

Background: Alpha‐fetoprotein (AFP) is an important marker for hepatocellular carcinoma (HCC). However, persistent elevation of AFP is found in patients with chronic liver diseases. The value of AFP‐L3, which is more specific than AFP, was examined in such patients. Methods: We enrolled patients without image‐detectable tumor, but with transient AFP value > 900 ng/mL (group A) or with persistent AFP value > 50 ng/mL for longer than 6 months (group B). Forty‐one patients with HCC and AFP value > 50 ng/mL were included as the HCC control group (group C). AFP‐L3 measurement was done by lectin‐affinity electrophoresis coupled with antibody‐affinity blotting. The study patients were followed with AFP, liver biochemistry and abdominal ultrasound at 3‐ to 6‐month intervals. Additional studies were done when a tumor was suspected. Results: One of 17 patients in group A and 13 of 39 patients in group B developed HCC within 2 years. When the cutoff value of AFP‐L3 ratio was 15%, both the sensitivity and specificity were 71% for prediction of HCC during the next 2 years in all patients. Ninety percent of tumors larger than 5 cm had AFP‐L3 > 15%, compared with only 60% for tumors smaller than 2 cm. Three patients in group A had AFP‐L3 ratio > 17.5%. One patient developed HCC 10 months later; the other 2 patients were associated with hepatic failure. Conclusion: AFP‐L3 provides a clue in HCC detection in patients with persistent elevation of AFP. However, AFP‐L3 could be highly elevated in severe hepatitis.

Septic Acute Cholecystitis

BACKGROUNDnBacteremia occurs frequently in cholangitis, but the incidence of bacteremia in acute cholecystitis has not previously been examined.nnnMETHODSnSeventy-eight cases (46 men and 32 women; mean age, 63 +/- 10 years) of acute cholecystitis with positive blood cultures were analyzed for clinical manifestation, bacteriology, and what consequences ensued. Seventy-eight non-bacteremic cholecystitis patients, matched for age and sex, served as the control group.nnnRESULTSnThe prevalence of bacteremia in acute cholecystitis was 7.65% (78 of 1020). A single microorganism was isolated from the blood and bile in 87.2% and 27.3%, respectively. The commonest organisms were Escherichia coli and Klebsiella pneumoniae. The source of bacteremia could be identified from the infected bile in 80% of cases. Compared with the non-bacteremia group, significant increases in liver biochemical test results (aspartate and alanine aminotransferases and bilirubin, and so forth), more complications (acute renal failure and septic shock), and higher mortality (9.0%) were found in the bacteremic group.nnnCONCLUSIONnAcute cholecystitis is not often complicated by bacteremia, but when bacteremia is present, morbidity and death more consistently ensue.

Sequential invasions of pancreatic pseudocysts in pancreatic tail, hepatic left lobe, caudate lobe, and spleen

A 66-year-old male patient without a history of risk factors for pancreatitis suffered from pancreatitis and developed pseudocyst. During the course of treatment and follow-up, the pseudocyst was found to have migrated through the pancreatic tail, left hepatic lobe, caudate lobe, and spleen on abdominal sonography and computed tomography scan. Finally, emergent laparotomy was done for splenic abscess and removal of infected pseudocyst in the spleen and lesser sac of the abdomen. The patient made a full recovery after operation.

Endoscopic injection sclerotherapy with 1.5% Sotradecol for bleeding cardiac varices

The authors retrospectively studied the efficacy of endoscopic injection sclerotherapy (EIS) with 1.5% Sotradecol (STD) in patients with bleeding cardiac varices (CV). Case histories of 27 patients with large, isolated, bleeding CVs were reviewed. Case records of another 27 patients with isolated esophageal varices (EV), matched for age, sex, and year EIS was performed, were selected from a computer data bank as controls. Using a small volume (2-4 ml) of injection per vessel, the rate of immediate control of bleeding was 66.7% (18 of 27) in the CV group and 70.4% (19 of 27) in the EV group. The early rebleeding rate was higher for patients in the EV group (48.1%, 13 of 27) than for those in the CV group (18.5%, 5 of 27) (p = 0.0209). On the other hand, it was more difficult to control the rebleeding from CV (p = 0.00494). In terms of mortality, there was no statistically significant difference between the CV and EV groups (33.3 versus 29.6%) within 1 week after EIS, but the 1-month post-EIS mortality rate was significantly higher (p = 0.0278) in the CV group (18 of 27, 66.7%) than in the EV group (10 of 27, 37.0%). Among those in the CV group who died of late complications within 1 month after EIS, three died of recurrent hemorrhage, five of infection, and one of viscus perforation. In the EV group, only two patients died of infection. Thus, it was concluded that EIS with small volumes (2-4 ml) of 1.5% STD was equally effective in controlling immediate bleeding from CV and EV. However, it was more difficult to control early rebleeding from CV, and the mortality and complications within 1 month after EIS were significantly higher in patients with CV. These observations are currently under careful study and evaluation.