An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti-viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3 , basal core promoter (BCP) mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life-long anti-viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life-long surveillance for HCC with alpha-fetoprotein (AFP) testing and abdominal ultrasound examination at 6-month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3-month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence. CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.

Prevention of hepatocellular carcinoma and its recurrence with anti-hepatitis B viral therapy.

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) should be prevention of Hepatocellular carcinoma (HCC). The discovery of the hepatitis B virus (HBV) in 1965 and eventual development of antiviral drugs during the past decades, has led us to observe a remarkable success in arresting the disease progression. More importantly, we have been able to prevent secondary HCC formation with antiviral therapy. Currently HCC is the second most common cause of cancer-related death, worldwide, accounting for more than 700,000 deaths each year. Most of the burden of disease (85%) is observed in the HBV endemic regions. It is thought that HBV contributes to HCC by directly modulating pathways that promote the malignant transformation of hepatocytes. Primary prevention of HBV infection by vaccination has been effective in reducing the incidence of HCC. On the other hand in people already infected with HBV, there is abundant evidence that antiviral therapies with the aim to suppress or eliminate HBV replication, can slow progression or even reverse liver damage, therefore, preventing HCC formation. Antiviral therapies also play an important role in preventing tumor recurrence in patients who undergo chemotherapy, ablative therapy, local resection, liver transplant or palliative treatment for HCC. This review will evaluate the mechanisms of HBV induction of HCC and the role of antivirals in both primary and secondary prevention of HCC.

Clinical trial: a phase II, randomized study evaluating the safety, pharmacokinetics and anti-viral activity of clevudine for 12 weeks in patients with chronic hepatitis B.

BACKGROUND: Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics. AIM: To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor. METHODS: A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off-treatment follow-up. Patients had chronic HBV infection, were nucleoside-naïve without co-infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method. RESULTS: A total of 31 patients were enrolled into the 10 mg (n = 10), 30 mg (n = 11) and 50 mg (n = 10) groups, respectively. At week 12, the median VL change was -3.2, -3.7 and -4.2 log(10) copies/mL (-0.64, -0.74 and -0.84 log(10) IU/mL) in the 10, 30 and 50 mg groups, respectively (P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half-life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound. CONCLUSION: Clevudine appears to be a potent and tolerable (over 12 weeks) anti-viral and the optimal dosage appears to be 30 mg once daily.

Active antiviral therapy for chronic hepatitis B and hepatocellular carcinoma.

The ultimate goal of treatment for chronic hepatitis B (CHB) is to prevent hepatocellular carcinoma (HCC). During the last decade, great strides have been made in the treatment of hepatitis B virus (HBV) infections. Six highly effective anti-HBV agents are currently available and more agents are on the horizon. Prospective and retrospective studies of large numbers of CHB patients with advanced liver disease, including cirrhosis, have demonstrated that the treatment with lamivudine not only delays the disease progression but also reduces the incidence of HCC. In a large prospective study of 3,653 HBV carriers in Taiwan, 164 persons developed HCC in a 12-year follow-up period; an extensive analysis of their condition led to the conclusion that the most important risk factor for HCC is an increased serum level of HBV DNA >10,000 copies/mL regardless of the HBeAg status, alanine aminotransferase levels or presence of cirrhosis. The incidence of HCC correlated with serum HBV DNA level at entry in a dose-response relationship. These pivotal studies re-emphasize the need for an active anti-HBV therapy for CHB patients with viral replication as the ultimate prevention and/or delay for the development of HCC.

Symptomatology and health attitudes of chronic hepatitis B patients in the USA.

This study was conducted to understand the symptomatology, attitudes, and behaviours of chronic hepatitis B (CHB) patients in the USA. CHB patients enrolled in this study were recruited through multiple methods, including newspaper advertisements. Interviews were conducted in multiple languages, and all participants had a history of CHB infection for at least 6 months. Patients with documented human immunodeficiency virus or hepatitis C virus coinfection were excluded from data analyses, resulting in a total study population of 258 respondents who completed interviews between April and June 2004. The majority of monoinfected patients were male (57%) and non-Asian (92%, including 52% Caucasian, 32% African American and others). Length of diagnosis was 5.8 years for all participants (9.1-year Asian and 5.1-year non-Asian). Ninety-five per cent of CHB patients reported symptoms of differing severity in the 12 months prior to the survey. The most common symptoms included fatigue/loss of energy (90%) and loss of appetite (79%). Non-Asian patients described greater symptomatology, and were more likely than Asians to consider CHB an overriding concern in their daily activities. Patients were treated either currently or previously with interferon (IFN) described greater symptomatology than those treated without IFN. Survey results indicate that CHB patients may have greater symptomatology than recognized. Disease perceptions and treatment attitudes differ between Asian and non-Asian ethnic groups, with the former appearing to be more accepting and less concerned about the disease. Additional research about CHB symptomatology and health attitudes by ethnicity is needed to ensure that individuals with CHB are educated on the potential health risks and the availability of current treatment options.

Histological outcome during long-term lamivudine therapy.

BACKGROUND & AIMS: One year of lamivudine for chronic hepatitis B results in histologic improvement. We aimed to assess the histological impact of longer-term treatment. METHODS: Sets of 3 liver biopsies, from 63 patients before and after 1 year of randomized lamivudine treatment and after 2 years of further open-label treatment, were assigned Histologic Activity Index scores under code. RESULTS: At the end of year 1, 36/63 (57%) showed > or =2 point improvement and 24/63 (38%) no change in necroinflammatory activity; after 2 additional years of lamivudine, 38/63 (60%) remained stable and 12/63 (19%) continued to improve. Worsening occurred in similar proportions of patients with and without YMDD (tyrosine, methionine, aspartate, aspartate) variants. After all 3 years of lamivudine treatment, 35/63 (56%) of patients showed improvement, 21/63 (33%) no change, and 7/63 (11%) worsening. Those without, compared with those with, YMDD variants were more likely to improve (17/22 [77%] vs. 18/41 [44%]) and less likely to deteriorate (1/22 [5%] vs. 6/41 [15%]). Patients with YMDD variants for >2 years were least likely to improve (8/22 [36%]). Bridging fibrosis improved by > or =1 level in 12/19 (63%), and cirrhosis improved (score of 4 to < or =3) in 8/11 (73%). Only 1/52 [2%]) showed progression to cirrhosis, and 3/34 (9%) showed progression to bridging fibrosis (all with YMDD variants). CONCLUSIONS: Three years of lamivudine therapy reduces necroinflammatory activity and reverses fibrosis (including cirrhosis) in most patients. The emergence of YMDD variants blunts histologic responses; therefore, extended-duration YMDD variants may require additional therapies to maintain the histological benefit of treatment.

Hepatocellular carcinoma after systemic chemotherapy: gadolinium-enhanced mr measurement of necrosis by volume histogram.

As a preliminary study, we measured the necrosis of advanced hepatocellular carcinoma (HCC) by volume histogram after systemic chemotherapy and correlated it with clinical data. Five patients with advanced HCC secondary to chronic hepatitis and cirrhosis underwent pretreatment and posttreatment MR examination on a 1.5 T MR scanner following systemic chemotherapy. MR sequences included dynamic enhanced fast spoiled gradient echo 3D images. Clinical response to chemotherapy, as determined by MR images, was measured as changes of both the total tumor volume and the percent of tumor necrosis by volume histogram algorithm. Four of five patients had clinical improvement. Three of these patients had no or minimal change of tumor volume; however, there was an increase in tumor necrosis in follow-up MR image. One patient of five with no change in tumor necrosis had no response and died at 3 months. Serial MR images showed increased irregular necrosis of advanced HCC after systemic chemotherapy, but stable volume, in patients who responded clinically to systemic chemotherapy.

A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.

Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.

Biological aspects of neuroblastomas identified by mass screening in Quebec.

BACKGROUND: Neuroblastoma has several characteristics that suggest that preclinical diagnosis might improve outcome. Therefore, the Quebec Neuroblastoma Screening Project was undertaken from 1989 to 1994 to examine infants at 3 weeks and 6 months by measuring urinary catecholamine metabolites. PROCEDURE: Over the 5-yr period, 45 tumors were detected by screening, 20 were identified clinically prior to the third week, and 64 were identified clinically at a later time. We analyzed available tumors for Shimada histopathology, tumor ploidy, MYCN copy number and serum ferritin. RESULTS: Of the tumors detected by screening, only 2 of 45 tested had unfavorable histology, 2 of 45 had diploid or tetraploid DNA content, 0 of 43 had MYCN amplification, and 4 of 44 had elevated serum ferritin. All of these patients are alive and well. The 20 patients detected prior to the 3-week screen had similar biological characteristics. In contrast, of the patients detected clinically after 3 weeks of age, 19 of 51 testedhad unfavorable histology, 25 of 66 had diploid or tetraploid tumors, 12 of 56 had MYCN amplification, and 14 of 54 had elevated ferritin. CONCLUSIONS: The difference between the screened and clinically detected cases was highly significant for each biological variable. Preliminary data on other biological variables, such as neurotrophin expression and allelic loss on 1 p in these patients are consistent with the above findings. These data suggest that mass screening for neuroblastoma at or before 6 months of age detects almost exclusively tumors that have favorable biological characteristics, many of which might have regressed spontaneously. Thus, continued mass screening for neuroblastoma at 6 months is unlikely to accomplish its intended goal, and should probably be discontinued.

Hepatic iron deposition on MR imaging in patients with chronic liver disease: correlation with serial serum ferritin concentration.

BACKGROUND: To evaluate the relationship between magnetic resonance (MR) imaging grading of iron deposition and serial serum ferritin concentration in patients with chronic viral liver diseases. METHODS: In 80 patients with viral hepatitis and cirrhosis, MR images including T2*-weighted gradient echo images (echo time > or = 6.5 ms) were reviewed. The grades of parenchymal iron deposition and iron-containing nodules in the liver and spleen and the liver-to-muscle and spleen-to-muscle signal intensity ratios were compared with the most recent, the mean, the lowest, and the highest values from all available serum ferritin levels. RESULTS: The serum ferritin concentration was significantly correlated with the grades of iron deposition in liver and spleen and with the grades of iron-containing nodules seen on MR images (p < 0.05). Liver-to-muscle signal intensity ratio was weakly correlated with the ferritin concentrations. Among categories of ferritin concentration, correlation with MR grades was highest for mean ferritin concentration (r = 0.487, p < 0.001). CONCLUSION: MR imaging grades of hepatic iron and siderotic nodules correlate with serum ferritin, especially with the mean levels.

Depression in Korean immigrants with hepatitis B and related liver diseases.

The authors evaluated 50 Korean immigrants who had chronic viral hepatitis or who were healthy carriers for the hepatitis B virus in terms of the relationships between their depression scores, psychosocial stressors, social support, and biological markers of dysfunction. All participants completed a questionnaire, describing their worries and concerns, and the shortform of the Beck Depression Inventory (BDI-sf). Hepatic transaminases, albumin levels, and prothrombin times were measured during routine clinic follow-up visits and were abstracted from the medical record. Values recorded within 3 months before and within 3 months after the psychiatric interview were correlated with BDI scores. BDI-sf total scores were significantly associated with transaminase elevations (P<0.001) both before and after BDI-sf administration. BDI scores were not associated with other measures of liver dysfunction or other medical causes of depression. Patients with higher BDI-sf total scores had more psychosocial stressors (P = 0.008) and lower Global Assessment of Functioning (GAF) scores (P = 0.000).

Lamivudine as initial treatment for chronic hepatitis B in the United States.

BACKGROUND AND METHODS: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). RESULTS: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sustained normalization of serum alanine aminotransferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. CONCLUSIONS: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were generally sustained after treatment.

Viral-induced cirrhosis: grading of severity using MR imaging.

OBJECTIVE: The purpose of this study was to determine whether MR imaging can be used to grade the severity of cirrhosis. MATERIALS AND METHODS: The MR examinations of 46 patients with cirrhosis were retrospectively reviewed independently by two radiologists and correlated with clinical severity assessed by Child-Pugh classification. MR imaging analysis by reviewers who were unaware of clinical status included comparison of volume indexes (computed as the product of three axis measurements) of the spleen and each segment of the liver, and changes in hepatic contour, iron or fat deposition, and presence of varices and collaterals. RESULTS: Volume index of the spleen and the presence of ascites and varices were significantly and positively correlated (p = .008, .002, .0001, respectively) with the clinical severity of cirrhosis (Child-Pugh classifications), and volume indexes of the posterior, medial, and lateral segments of the liver were significantly and inversely correlated (p = .001, .049, .041, respectively). On an MR scoring system based on four items (volume index of the spleen; volume index of posterior + medial + lateral segments; presence of ascites; and presence of varices and collaterals), averaged total MR scores were 2.5 +/- 0.3, 4.9 +/- 0.6, and 7.9 +/- 0.8 for Child-Pugh grades A, B, and C, respectively (p < .0001). The accuracy of MR scoring in distinguishing between clinical Child-Pugh grade A cirrhosis and further grades was 89%, the sensitivity was 93%, and the specificity was 82%. CONCLUSION: An MR scoring system can be used to grade the severity of cirrhosis.

Hepatocellular carcinoma: association with increased iron deposition in the cirrhotic liver at MR imaging.

PURPOSE: To determine whether the frequency of hepatocellular carcinoma (HCC) in patients with cirrhosis is affected by hepatic iron deposition as detected with magnetic resonance (MR) imaging. MATERIALS AND METHODS: In a retrospective search of MR imaging and histopathology records, 196 patients with histopathologically proved cirrhosis and with (n = 80) or without (n = 116) HCC who underwent T2-weighted conventional or fast spin-echo and gradient-echo (GRE) (echo time > or = 6.0 msec) imaging were identified. MR images were qualitatively and quantitatively evaluated for diffuse hepatic iron deposition and siderotic regenerative nodules to assess their correlation with the presence of HCC. RESULTS: Hepatic parenchymal iron deposition was seen in 79 (40%) patients, and iron deposition in regenerative nodules was seen in 71 (36%) at MR imaging. The mean signal intensity ratio of GRE images in patients with hepatic iron deposition was significantly lower than that in patients without it (P < .001). The frequency of HCC in patients with iron deposition in regenerative nodules (52% [37 of 71 patients]) was significantly higher (P = .015) than that in patients without iron in regenerative nodules (34% [43 of 125 patients]). CONCLUSION: The occurrence of HCC may be associated causally with iron deposition in regenerative nodules in patients with cirrhosis. MR imaging can enable detection of iron deposition in regenerative nodules as a possible risk factor for the development of HCC.

Progressive viral-induced cirrhosis: serial MR imaging findings and clinical correlation.

PURPOSE: To determine which magnetic resonance (MR) imaging findings of cirrhosis change as disease severity progresses. MATERIALS AND METHODS: Seventy-six abdominal MR imaging studies in 38 patients (two per patient) with Child-Pugh grade A cirrhosis were retrospectively reviewed. All patients were followed up clinically and with MR imaging for 12 months or longer. MR images were used to determine volume indexes of the spleen and of each liver segment, as well as changes in hepatic contour, iron or fat deposition, and presence of varices and collateral vessels. RESULTS: During follow-up in patients with progressive cirrhosis (n = 13), the volume indexes of the anterior, posterior, and medial segments of the liver decreased significantly (P = .011, .013, .002, respectively), and the number of varices and collateral vessels increased significantly (P = .018). In patients with stable cirrhosis (n = 25), the volume indexes of the spleen, caudate lobe, and lateral segment increased significantly (P = .032, .018, .003, respectively). The atrophic index was significantly greater in progressive cirrhosis than in stable cirrhosis (P = .009). CONCLUSION: Progressive atrophy of the right hepatic lobe and the medial segment correlated with progression of clinical severity of cirrhosis, whereas increasing size of the caudate lobe and the lateral segment correlated with stability.

Interferon-alpha2b therapy is efficacious in Asian-Americans with chronic hepatitis B infection: a prospective controlled trial.

Chronic hepatitis B virus infection is endemic in Asian communities in the United States. The purpose of the current study was to compare the antiviral efficacy of interferon-alpha2b in a group of adult Asian patients chronically infected with hepatitis B with active replication compared to a control group of Caucasian patients treated with the same regimen. Patients with entry aminotransferase (ALT) levels greater than three times the upper limit of normal received interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients with pretreatment ALT levels 1.5-3 times the upper limit of normal received prednisone for a total of six weeks prior to interferon starting at 60 mg daily with reduction in dosage by 20 mg every two weeks with a two-week period between finishing prednisone and starting interferon-alpha2b. Eight (62%) of the 13 Asians and six (60%) of the 10 Caucasians cleared HBeAg and HBV DNA from serum (NS). By the end of one year of follow-up after therapy, four (67%) of six Caucasian responders but none of the Asian responders had cleared hepatitis B surface antigen from serum (P < 0.05). Loss of serum markers of active replication appeared less durable in the Asian responders compared to the Caucasians with reappearance of serum HBeAg in two (25%) of eight of the former but only one (17%) of the latter group. Three other Asian patients subsequently redeveloped HBeAg in serum. It is concluded that adult Asian-Americans have an identical initial response rate to antiviral therapy with interferon-alpha2b; however, the response may be less durable and does not usually lead to loss of HBsAg.

Compensated cirrhosis due to viral hepatitis: using MR imaging to predict clinical progression.

OBJECTIVE: The goal of our study was to determine the relative value of multiple MR features in predicting clinical progression of disease in patients with compensated cirrhosis. MATERIALS AND METHODS: The MR examinations of 23 patients with compensated cirrhosis (Child A) were retrospectively reviewed independently by two radiologists and correlated with clinical progression after follow-up of all patients for more than 12 months each (12-87 months: average, 39 months) by the same experienced hepatologist. Clinical progression was defined as an increase of the Child grade or the Pugh score by at least two points (5- to 15-point scale). In the initial MR study of each patient, the following MR findings were assessed by each radiologist independently: volume indexes of the spleen and each segment of the liver (based on three-axis measurements), nodular surface, regenerative nodules, ascites, iron or fat deposition, and varices or collaterals. RESULTS: The volume index of the spleen was the most accurate predictor of clinical progression (p = .001), the next most accurate was the number of sites of varices or collaterals (p = .002), and the third most accurate was the ratio of caudate lobe to right lobe volume index (p = .02). Other MR findings failed to correlate with clinical progression. CONCLUSION: As revealed on MR imaging, the volume index of the spleen, the severity of varices, and the volume index ratio of caudate lobe to right lobe can be used to help predict clinical progression of disease in patients with compensated cirrhosis.

Early hepatocellular carcinoma that develops within macroregenerative nodules: growth rate depicted at serial MR imaging.

PURPOSE: To assess by means of magnetic resonance (MR) imaging the growth rate of early hepatocellular carcinoma (HCC) that develops within macroregenerative nodules. MATERIALS AND METHODS: Serial MR imaging was performed in five patients with six macroregenerative nodules that demonstrated a "nodule-within-nodule" pattern (small intranodular focus). The diameter and volume increases of the internal foci at different time intervals were estimated. Average doubling time (DT) was then calculated. RESULTS: The tiny foci within macroregenerative nodules exhibited rapid growth, with average DTs of 29 weeks for diameter and 9.5 weeks for volume. HCC was proved histopathologically in all five patients. CONCLUSION: HCC, which manifests initially as a small focus within a macroregenerative nodule, has the potential for rapid growth. This growth rate should be considered when plans are formulated for follow-up and/or treatment.

Cirrhosis: multiobserver analysis of hepatic MR imaging findings in a heterogeneous population.

To investigate the magnetic resonance (MR) imaging findings of hepatic cirrhosis and the potential of MR imaging in differentiating cirrhosis from other hepatic abnormalities, three observers with different levels of expertise in MR imaging (specialist, experienced radiologist, and novice with special training) reviewed hepatic MR imaging examinations of 52 patients with biopsy-proved presence (n = 29) or absence (n = 23) of cirrhosis. All examinations included motion-compensated T1-weighted, T2-weighted, and flow-sensitive gradient-echo images. For all three observers, linear signal irregularity was more accurate than other findings. For the final diagnosis of cirrhosis, the specialist was most sensitive (76% at high threshold, 97% at low threshold), followed by the novice with special training (31% and 79%, respectively). Specificity was 100% for all observers at high threshold and 78%, 96%, and 87% for expert, experienced, and trained novice observers, respectively, at low threshold. Sensitivity did not vary regardless of severity of fibrosis, as determined independently by a hepatopathologist. MR imaging has the potential of offering a comprehensive noninvasive evaluation of patients with suspected cirrhosis, but considerable expertise is required at present.