Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy.

AIMS: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). MATERIALS AND METHODS: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of ≥100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. RESULTS: After a median follow-up of 26.7 ± 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and ≥100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of ≥100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count ≤10(5)/mm(3) (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. CONCLUSIONS: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma.

AIM: Serum alpha-fetoprotein (AFP) is the most important tumor marker for hepatocellular carcinoma (HCC). Previous reports indicated that HCC was also associated with increased levels of interleukin (IL)-6, IL-10 and hepatocyte growth factor (HGF). This study investigated the role of these cytokines as tumor markers for HCC. METHOD: A total of 128 adults were prospectively enrolled and categorized into four groups: normal subjects (n=29), chronic hepatitis B or C (n=50), non-HCC tumors (n=23) and HCC (n=26). Serum AFP, IL-6, IL-10 and HGF levels were determined in all subjects. RESULTS: The expression of IL-6 or IL-10 (> or =3 pg/ml), or high level of HGF (>1000 pg/ml) or AFP (>20 ng/ml) was observed in only 0-3% of normal subjects. Patients with HCC more frequently had higher IL-6 and IL-10 levels (p<0.05), whereas HGF levels in HCC patients were not significantly elevated compared to patients with chronic hepatitis or non-HCC tumors. Among patients with low (<20 ng/ml) AFP level, IL-6 or IL-10 expression was significantly associated with the existence of HCC (p<0.05). Patients with large (>5 cm) HCC more often had increased IL-6, IL-10 or AFP levels (p values all <0.05). CONCLUSIONS: Serum levels of IL-6 and IL-10 are frequently elevated in patients with HCC but not in benign liver disease or non-HCC tumors. IL-6 and IL-10 may help identify a subset of HCC patients with low AFP level, and may serve as complementary tumor markers in these patients.

Survival benefit of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma larger than 10 cm in diameter.

BACKGROUND: The safety and survival benefit of transcatheter arterial chemoembolization for patients with huge hepatocellular carcinoma is uncertain. AIM: To evaluate the role of embolization in unresectable hepatocellular carcinomas larger than 10 cm. METHODS: Twenty-six consecutive patients who had an unresectable hepatocellular carcinoma larger than 10 cm and refused aggressive treatment, were enrolled as the control group. Another 31 patients matching with the control cases and undergoing embolization for huge unresectable hepatocellular carcinoma served as the embolization group. Survival between the two groups was compared. RESULTS: Two patients (7%) died from embolization-related complications. Patients in embolization group had longer survival than those in control group (median survival: 9.13 vs. 2.1 months). The 1-, 3- and 5-year survival rates in embolization group were 42%, 13% and 7% respectively. The 1- and 3-year survival rates for patients in control group were 8% and 0% respectively. In multivariate analysis, embolization and prothrombin ratio < or =1.2 were two independent factors associated with a better survival. CONCLUSIONS: Embolization-related mortality is low for huge hepatocellular carcinoma, and the technique provides survival benefit in patients with unresectable hepatocellular carcinomas larger than 10 cm in diameter.

Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis.

Chronic hepatitis B virus (HBV) infection and the integration of its X gene (HBx) are closely associated with the development of hepatocellular carcinoma (HCC). The integrated HBx frequently is truncated or contains point mutations. Previous studies indicated that these HBx mutants have a diminished co-transactivational activity. We have compared the effects of wild-type (wt) HBx and its naturally occurring mutants derived from human HCCs on transcriptional co-transactivation, apoptosis and interactive effects with p53. We demonstrated that overexpression of mutant, but not wt HBx, is defective in transcriptional co-transactivation of the NF-kappaB-driven luciferase reporter. By using a microinjection technique, the HBx mutants were shown to have an attenuated pro-apoptotic activity. This deficiency may be attributed to multiple mutations in the co-transactivation domain of HBx, that leads to decreased stability of the translated product. However, wt or mutant HBx bind to p53 in vitro and retain their ability to block p53-mediated apoptosis in vivo, which has been implicated as its major tumor suppressor function. The abrogation of p53-mediated apoptosis by integrated HBx mutants may provide a selective clonal advantage for preneoplastic or neoplastic hepatocytes and contribute to hepatocellular carcinogenesis.

The role of transcatheter arterial embolization for patients with unresectable hepatocellular carcinoma: a nationwide, multicentre study evaluated by cancer stage.

BACKGROUND: Transcatheter arterial embolization is a major palliative treatment for unresectable hepatocellular carcinoma, but the survival benefit of transcatheter arterial embolization is controversial. AIM: To evaluate the role of transcatheter arterial embolization in different stage of unresectable hepatocellular carcinoma and to select patients who can get the best benefit from the treatment. METHODS: From 1991 to 1995, 476 patients who had unresectable hepatocellular carcinoma from four medical centres in Taiwan were enrolled. Among them, 425 underwent transcatheter arterial embolization, and 51 received supportive treatment alone. The survivals between the two groups were compared. RESULTS: Among the 476 patients, transcatheter arterial embolization can significantly prolong survival. The 1-, 2-, and 5-year survival rates for patients who underwent transcatheter arterial embolization were 60.2%, 39.3%, and 11.5%; and the rates for patients who underwent supportive treatment were 37.3%, 17.6%, and 2%, respectively (P = 0.0002). The survival benefit of transcatheter arterial embolization was observed in patients between Cancer and the Liver Italian Program 0 and Cancer and the Liver Italian Program 4. In multivariate analysis, transcatheter arterial embolization, tumour size <5 cm and earlier Cancer and the Liver Italian Program stage were independent factors associated with a better survival. CONCLUSIONS: For patients who fulfilled the criteria of transcatheter arterial embolization, embolization can serve as a primary treatment for patients with unresectable hepatocellular carcinoma. The survival benefit of transcatheter arterial embolization is regardless of tumour stages.

Acute renal failure after transarterial chemoembolization for hepatocellular carcinoma: a retrospective study of the incidence, risk factors, clinical course and long-term outcome.

BACKGROUND: Transarterial chemoembolization is effective for hepatocellular carcinoma. Acute renal failure may occur after transarterial chemoembolization because of radiocontrast agent, but its clinical aspects are unknown. AIM: To investigate the incidence, risk factors and outcome of acute renal failure, defined as increase of serum creatinine > 1.5 mg/dL, after transarterial chemoembolization. METHODS: A total of 235 hepatocellular carcinoma patients with 843 transarterial chemoembolization treatment sessions were analysed. RESULTS: Acute renal failure developed in 56 (23.8%) patients and the estimated risk of developing acute renal failure was 6.6% in each treatment session. Comparison between the episodes of transarterial chemoembolization with and without acute renal failure by using the generalized estimating equation disclosed that Child-Pugh class B (odds ratio: 2.6, P = 0.007) and treatment session (odds ratio: 1.3; P < 0.0001) were independent risk factors of acute renal failure. Twenty-seven patients had prolonged renal function impairment. Multivariate analysis by generalized estimating equation showed that Child-Pugh class B (odds ratio: 4.3, P = 0.0004) and diabetes mellitus (odds ratio: 5.2, P < 0.0001) were linked with prolonged acute renal failure, which independently predicted a decreased survival (relative risk: 2.3, P = 0.002). CONCLUSIONS: Acute renal failure after transarterial chemoembolization appears to be dose-related and is associated with the severity of cirrhosis. Patients with diabetes mellitus or Child-Pugh class B more frequently develop prolonged acute renal failure, which in turn is a poor prognostic predictor.

Long-term outcome of kidney transplantation in patients with hepatitis C virus infection.

BACKGROUND/AIMS: The impact of HCV (hepatitis C virus) infection on the long-term outcome of kidney transplant patients is controversial. METHODOLOGY: Eighty-four renal allograft recipients who were seronegative for hepatitis B surface antigen and had been screened for antibody to hepatitis C virus (anti-HCV) were included. The outcome and survival were compared between anti-HCV-positive (n = 30, group 1) and anti-HCV-negative (n = 54, group 2) kidney transplant patients. Group 1 patients were further compared to 52 anti-HCV-positive end-stage renal disease patients (group 3) who were on chronic dialysis. RESULTS: Group 1 patients had a higher prevalence of chronic hepatitis than group 2 and group 3 patients did (67% vs. 2% and 31%). Liver-related complications and deaths between group 1 and group 2, and group 1 and group 3 patients were not significantly different. The comparisons of the long-term survival between these groups showed no significant differences, despite group 3 patients had a higher overall mortality rate. Cox regression analysis confirmed that age more than 45 years was the only independent factor that affected survival in anti-HCV-positive end-stage renal disease patients with or without kidney transplantation. CONCLUSIONS: HCV infection is not a contraindication to kidney transplantation. For anti-HCV-positive end stage renal disease patients, survival is better in younger patients, and is not influenced by kidney transplantation or continuing dialysis.

A prognostic model for patients with hepatocellular carcinoma within the Milan criteria undergoing non-transplant therapies, based on 1106 patients.

BACKGROUND: The Milan criteria are used to select candidates with small hepatocellular carcinoma (HCC) for liver transplantation. Due to severe shortage of donors, majority of patients within the Milan criteria need to seek alternative treatments. AIM: To propose a prognostic model for these patients undergoing non-transplant therapies. METHODS: A total of 1106 HCC patients, who were within the Milan criteria and received non-transplant therapies were retrospectively analysed. Patients were randomly assigned to the derivation and validation set according to treatments. A prognostic model was constructed from independent predictors of survival identified in the multivariate Cox model of the derivation set and was confirmed in the validation set. RESULTS: In the Cox model, serum bilirubin ≥1.5 mg/dL [risk ratio (RR): 1.525, P = 0.016], α-fetoprotein (AFP) ≥100 ng/mL (RR: 1.728, P < 0.001), mild ascites (RR: 1.705, P = 0.025) and moderate/severe ascites (RR: 4.163, P < 0.001) were independent predictors of poor survival in the derivation set (n = 553). A prognostic model with a total of 0-4 points was derived with the sum of three variables: 1 point each for bilirubin ≥1.5 mg/dL, AFP ≥100 ng/mL and mild ascites, and 2 points for moderate/severe ascites. This scoring system accurately predicted the survival in the validation set (n = 553; P < 0.001). The model consistently discriminated the survival in patients stratified by curative and noncurative treatments (both P values <0.001). CONCLUSION: The newly proposed prognostic scoring model, based on serum bilirubin and AFP level, and severity of ascites, is informative to predict the survival in non-transplant HCC patients within the Milan criteria.

Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis.

BACKGROUND AND AIM: The model for end-stage liver disease (MELD) is used to predict the outcome of patients with cirrhosis. Incorporation of serum sodium (Na) into MELD may further increase its prognostic ability. Two Na-containing MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability. This study compared the predictive accuracy of these models for acute decompensated hepatitis. METHODS: We investigated the outcome of 182 patients with acute decompensated hepatitis. RESULTS: Twenty (11%) patients died at 3 months. The MELD-Na and MELDNa both had significantly higher area under the receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na: 0.908, MELDNa: 0.895, MELD: 0.823, p=0.004 and 0.001, respectively). Among 96 patients without specific antiviral treatment, the MELD-Na and MELDNa consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa: 0.882, MELD: 0.810, p=0.008 and 0.004, respectively). Three independent indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence interval [CI]: 1.72-18.7), serum albumin<3.7 g/dL (OR: 5.68, 95% CI: 1.18-27.03) and serum sodium (Na)<138 mequiv./L (OR: 10.0, 95% CI: 2.08-47.62), were associated with 3-month mortality. CONCLUSION: MELD-Na and MELDNa provide better prognostic accuracy than the MELD for patients with acute decompensated hepatitis. The adequacy of liver reserve determines the outcome of these patients.

The MELD-Na is an independent short- and long-term prognostic predictor for hepatocellular carcinoma: a prospective survey.

BACKGROUND AND AIM: Serum sodium has been suggested to incorporate into the model for end-stage liver disease to enhance its prognostic ability for cirrhosis. A mathematical equation based on model for end-stage liver disease and sodium, known as "MELD-Na", was developed for outcome prediction for cirrhosis. The severity of liver cirrhosis is a key component to predict survival in patients with hepatocellular carcinoma. This study investigated the prognostic role of MELD-Na for hepatocellular carcinoma. PATIENTS AND METHODS: A total of 535 unselected hepatocellular carcinoma patients were prospectively enrolled to evaluate the performance of MELD-Na. RESULTS: The MELD-Na was better than model for end-stage liver disease in predicting 6-month mortality by comparing the area under receiver operating characteristic curve (0.782 vs. 0.761, p=0.101). MELD-Na, but not model for end-stage liver disease, was an independent predictor associated with 6-month mortality in multivariate logistic regression analysis (odds ratio: 1.14, p=0.001). In the survival analysis, MELD-Na also independently predicted mortality, with an additional risk of 4.3% per unit increment of the score (p<0.001). Patients with MELD-Na scores between 10 and 20 and scores >20 had 2.1-fold (p<0.001) and 7.5-fold (p<0.001) risk of mortality, respectively, compared to patients with a score <10 in the Cox proportional hazard model. CONCLUSION: The MELD-Na score is a feasible and independent prognostic predictor for both short- and long-term outcome predictions in patients with hepatocellular carcinoma.

Association of core promoter/precore mutations and viral load in e antigen-negative chronic hepatitis B patients.

Apart from core promoter A1762T/G1764A and precore G1896A mutations, other hepatitis B virus (HBV) mutants are detected in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to determine the effects of those mutants on clinical manifestation and viral loads of genotypes B and C HBV. Seventy-nine HBeAg-negative CHB patients with hepatitis flare were enrolled in this study and their HBV precore/core region were sequenced. Serial biochemical profiles and viral loads were assessed and compared. Fifty-three patients (67%) were infected by genotype B HBV and 26 (33%) were infected by genotype C HBV. The clinical manifestation and HBV viral loads were comparable between the two groups. However, genotype B was significantly associated with precore G1896A mutation (92.5%), and more mutations within nucleotide 1809-1817 were detected in patients infected by genotype B as compared with those infected by genotype C (18.9%vs 3.8%). Most of the cases had mutations at the -2, -3 or -5 position from the precore AUG initiation codon. Triple core promoter mutations T1753C/A1762T/G1764A [corrected] appeared to be linked to genotype C rather than genotype B HBV (19.2%vs 1.9%; P = 0.013). In multivariate analysis, the presence of either triple core promoter 1753/1762/1764 mutation or nucleotide 1809-1817 mutation was the only factor associated with lower HBV viral load (<70 Meq/mL) (odds ratio = 9.01; 95% CI 1.11-71.43; P = 0.04). In conclusion, minor HBV variants with mutations in the core promoter and precore region were detectable in genotypes B and C. Such HBV variants are genotype specific and related to viraemia levels.

Severe hyperbilirubinemia due to acute hepatitis A superimposed on a chronic hepatitis B carrier with glucose-6-phosphate dehydrogenase deficiency.

Taiwan is an endemic area for hepatitis A and B virus infections; nearly 90% of adults have serological markers for either virus. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is also common, ranging from 2% to 10%. We report the case of a 36-yr-old chronic HBV male carrier with G6PD deficiency who developed acute viral hepatitis A with severe hyperbilirubinemia and intravascular hemolysis. The hemolysis was in all likelihood the result of recent exposure to sulfa drugs. Fulminant hepatitis was the initial impression, because the peak serum total bilirubin concentration was alarmingly high, at 85.4 mg/dl. Exchange plasmapheresis was fresh frozen plasma was performed, and various laboratory studies gradually returned to near normal laboratory studies gradually returned to near normal over the next 3 wk. The patient made an uneventful recovery 1 month after admission.

Induction of complete tumor necrosis may reduce intrahepatic metastasis and prolong survival in patients with hepatocellular carcinoma undergoing locoregional therapy: a prospective study.

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous acetic acid injection (PAI) are effective locoregional therapies for hepatocellular carcinoma (HCC). This study aimed to investigate whether HCC patients who had initial complete response to these treatments had a subsequent lower risk of intrahepatic metastasis. PATIENTS AND METHODS: A total of 152 patients who underwent locoregional therapy (94 received PAI and 58 received both TACE and PAI) for HCC (tumor size < or =5 cm) were prospectively evaluated. RESULTS: In all, 60 (39%) patients had a complete tumor necrosis after treatment. The cumulative incidence of the development of intrahepatic metastasis was lower for patients with complete remission (P = 0.005) and for patients with smaller (< or =3 cm) tumor size (P = 0.083). Cox multivariate survival analysis showed that absence of complete remission [relative risk (RR) 2.7; 95% confidence interval (CI) 1.4-5.3; P = 0.003] was the only independent factor that predicted the occurrence of intrahepatic metastasis. Patients with complete remission had a significantly better long-term survival than those without (P = 0.002), and the occurrence of intrahepatic metastasis over time independently predicted a decreased survival (RR 3.2; 95% CI 2.0-6.1; P = 0.019). CONCLUSIONS: Induction of complete tumor necrosis in HCC patients undergoing locoregional therapy may decrease the risk of intrahepatic metastasis and improve survival.

Persistent retention of acetic acid is associated with complete tumour necrosis in patients with hepatocellular carcinoma undergoing percutaneous acetic acid injection.

BACKGROUND: Ultrasound (US)-guided percutaneous acetic acid injection therapy (PAIT) is effective for patients with hepatocellular carcinoma (HCC). This study aimed to determine the occurrence and predictive value of persistent intra-tumoral retention of acetic acid after PAIT. METHODS: We prospectively studied 60 (52 M, mean age 68 +/- 10 years) patients with 72 HCC nodules (45 < or = 3 cm) treated with PAIT. The presence of post-treatment persistent retention of acetic acid, defined as a homogeneous and highly hyperechoid mass in US appearance 3 days after completion of the treatment, was correlated with the treatment response. RESULTS: The mean size of the treated tumour was 2.9 +/- 1.0 cm (range 1.5-5 cm). Thirty (42%) HCC nodules showed complete tumour necrosis demonstrated by contrast-enhanced dynamic CT. Complete response was found in 22 (69%) of 32 nodules showing persistent intra-tumoral retention of acetic acid (P < 0.001). Small (< or = 3 cm) tumour size was also significantly associated with complete tumour necrosis (P = 0.001). There were no significant differences of the injection volume and treatment sessions between those with and without complete tumour necrosis in either small or large (> 3 cm) HCC (P > 0.1). Multivariate logistic regression analysis showed that persistent retention of acetic acid (odds ratio (OR) 10.4, 95% confidence interval (CI) 3.1-34.7; P < 0.001) and tumour size < or = 3 cm (OR 6.8, 95%, CI 1.8-25.8; P = 0.002) were independent factors predicting complete tumour necrosis. CONCLUSIONS: The presence of persistent retention of acetic acid is associated with a favourable response and may predict complete tumour necrosis after PAIT.

Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D.

The outcome of hepatitis D virus (HDV) superinfection varies among patients and in different geographical areas. To find out whether HDV genotype affects outcome, we used a simple genotyping method based on restriction-fragment length polymorphism with enzymes XhoI and SacII for cleavage of PCR products of the HDV genome. Of samples from 88 patients studied, the genotypes of 61 were confirmed by two methods--analysis with both enzymes or by combined restriction-enzyme and direct sequencing analyses--with consistent results. No genotype III HDV was detected among these patients. The majority of patients with acute HDV infection (35/41 [85%]) had genotype II HDV. Among the 41 patients with acute infection, four of six with genotype I had fulminant disease compared with two of 35 with genotype II. Among patients in chronic stage, cirrhosis or hepatocellular carcinoma were found in 12 of 18 with genotype I HDV and eight of 29 with genotype II. Thus genotype II was the predominant HDV genotype in this study in Taiwan. Genotype II HDV was less frequently associated with fulminant hepatitis at the acute stage or with an unfavourable long-term clinical outcome at the chronic stage than was genotype I.

Comparison of clinico-pathological features in hepatitis B virus-associated hepatocellular carcinoma with or without hepatitis D virus superinfection.

BACKGROUND/AIMS: Hepatitis D virus superinfection in hepatitis B virus carriers produces additional damage in an already injured liver. Earlier reports noted that the development of hepatocellular carcinoma may be accelerated in hepatitis D virus-superinfected patients. This study aimed to investigate the impact of hepatitis D virus on the clinical course of hepatitis B virus-associated hepatocellular carcinoma. METHODS: A total of 42 consecutive hepatocellular carcinoma cases seropositive for antibody against hepatitis D virus antigen (anti-HDV) were found from 1986 to 1994; the clinical manifestations, treatment and outcomes were compared with 255 consecutive hepatocellular carcinoma cases seropositive for hepatitis B virus surface antigen but seronegative for anti-HDV. RESULTS: The mean age was 60 years in both groups of patients. Other features, including sex, duration of follow-up, presence of cirrhosis or ascites, serum biochemistry, status of HBV-e antigen, and gross and microscopic tumor appearance, were not significantly different between the two groups. Though more patients in the anti-HDV-positive group underwent active treatment (operation or transcatheter arterial chemoembolization) than those in the anti-HDV-negative group (54.8% in 42 versus 34.9% in 255 cases, p = 0.02), the cumulative 4-year survival rates (9.5% versus 9.8%) were similar. For the anti-HDV-positive hepatocellular carcinoma patients, tumor size < 5 cm and active treatment were favorable prognostic predictors associated with survival > 18 months. CONCLUSION: Hepatitis D virus superinfection does not accelerate the development of hepatocellular carcinoma. The clinical manifestations were similar, and the outcome in anti-HDV-positive patients was not worse than in the general HBV-associated hepatocellular carcinoma patients, as long as they were diagnosed at an early stage and actively treated.

Diabetes mellitus as a risk factor of liver cirrhosis in patients with chronic hepatitis B virus infection.

Liver cirrhosis may occur in chronic hepatitis B surface antigen (HBsAg) carriers. Diabetes mellitus (DM)-associated chronic hepatitis may also occasionally lead to cirrhosis; however, its role in the course of chronic HBsAg carriers has not been studied. A cohort of 500 HBsAg carriers (398 men; mean age at entry, 42 +/- 15 years) were followed up longitudinally. After a mean follow-up of 5.8 +/- 3.3 years, 71 (14.2%: 70 men) patients developed cirrhosis. Increased risks of cirrhosis were found among men and the elderly (p < 0.001). Fifteen (21.1%) cirrhotic patients were noted to have had DM for 2-15 years before the development of cirrhosis. By contrast, only eight (1.9%; p < 0.001 ) of the patients without cirrhosis developed DM. When cirrhotic patients were compared to 102 age- and sex-matched non-cirrhotic controls, DM and elevation of serum alanine transaminase levels were found to be independent factors associated with the advent of cirrhosis in multivariate analysis. Other factors, including acute exacerbation, bridging hepatic necrosis, and superinfection by hepatitis C or D viruses, were insignificant. Our results suggest that DM may play a role in the progression to liver cirrhosis in chronic HBsAg carriers. High-risk subjects should be closely monitored for late complications.

Diagnostic value of anti-hepatitis D virus (HDV) antibodies revisited: a study of total and IgM anti-HDV compared with detection of HDV-RNA by polymerase chain reaction.

A high serum titre (> or = 1000 or > or = 5000) of total antibody to hepatitis D virus (anti-HDV) and positive for immunoglobulin (Ig)M anti-HDV have been used to represent HDV replication, while reverse transcription-polymerase chain reaction (RT-PCR) is currently the most sensitive assay for detecting HDV viraemia. The aim of the present study was to re-evaluate the correlation of total anti-HDV and IgM anti-HDV with HDV viraemia based on RT-PCR and to assess the clinical significance of these markers in acute and chronic HDV superinfection. Chronic HDV infection was defined as positive HDV-RNA by RT-PCR for more than 6 months, while total anti-HDV titre was defined by serial dilution. Of 178 hepatitis B virus (HBV) carrier patients studied, 119 cases had been anti-HDV positive for more than 6 months. Two-thirds (79/119) were positive for HDV viraemia by RT-PCR. Only half the chronic HDV viraemic patients had a high titre (> or = 1000) of total anti-HDV, and there was only moderate agreement (kappa = 0.41) between total anti-HDV titre/IgM anti-HDV and HDV-RNA and chronic HDV viraemia. Based on cross-sectional and longitudinal follow-up analyses, serum total anti-HDV titres > or = 100 appeared to be an excellent cut-off titre (kappa = 0.91) in differentiating chronic from acute HDV infection among viraemic patients. In summary, IgM and a high titre total of anti-HDV are not good markers of HDV viraemia, but an anti-HDV titre of > or = 100 appears to be an excellent marker for the differentiation of acute from chronic HDV superinfection.