Editorial Board: Emmet B. Keeffe, MD (Chair); M. Eric Gershwin, MD;

Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD;

Paul Martin, MD; Marion G. Peters, MD

HEPATOLOGY WATCH®

DIGESTIVE DISEASE WEEK HIGHLIGHTS

MAY 17-22, 2003, ORLANDO

 

PRIMARY BILIARY CIRRHOSIS (PBC)

Ursodeoxycholic acid (UDCA) therapy prior to liver transplantation (LT).  Fiona Gordon and colleagues reviewed clinical data obtained from the King's College Hospital Liver Transplant Database for PBC patients who underwent LT from February 1988 to July 2001.  Data were available for 63 PBC patients who had received UDCA and for 105 PBC patients who had not received UDCA prior to LT.  Thirty-four patients in the UDCA-treated group had been given UDCA therapy for >2 years pre-LT.  The mean time from diagnosis of PBC to LT was 8.9 ± 5.2 years compared to 5.8 ± 4.4 years for UDCA patients treated >2 years and UDCA-untreated patients, respectively (p = 0.002).  At LT, mean serum bilirubin, alkaline phosphatase, and INR values were significantly lower in the UDCA >2-year treatment group compared to the untreated group.  No differences between treatment groups were found for Child-Pugh scores, maximum encephalopathy scores, or number of patients with variceal bleeds.  These data suggest that UDCA therapy of PBC patients improves the biochemical profile and delays LT.  (Abstract T1607)

 

HEPATOCELLULAR CARCINOMA (HCC)

Rising incidence.  Hashem El-Serag and coworkers identified all histologically confirmed cases of HCC from 1975 to 1998 using data from the SEER (Surveillance, Epidemiology, and End Results) program.  Age-adjusted incidence rates (AIR) of HCC increased from 1.4/100,000 during 1975-1977 to 3.0/100,000 during 1996-1998 (an increase of 114%).  In addition, multivariate regression analysis confirmed an almost 2-fold increase in HCC incidence between 1975 and 1998.  The increased incidence of HCC affected most age, gender, and ethnic groups; however, the most striking increase (110%) was observed in white men between the ages of 45 and 49.  These findings are consistent with a true increase in HCC incidence.  The authors suggest that this increased HCC incidence may be due to HCV infection acquired early in life during the 1960s and 1970s.  (Abstract 8)

 

CIRRHOSIS

Obesity as a risk factor for death or hospitalization.  George Ionnou and others utilized data from the first National Health and Nutrition Examination Survey and Epidemiologic Follow-Up Study (11,465 persons aged 25-74 years without evidence of cirrhosis at study entry) to determine if increased body mass index (BMI) in the general population is associated with cirrhosis-related death or hospitalization.  Participants were categorized into the following groups by baseline BMI measurements: normal-weight (BMI <25, n = 5,752); overweight (BMI 25 to <30, n = 3,774); and obese (BMI ³ 30, n = 1,939).  Overall, death or hospitalization due to cirrhosis occurred in 89 participants during 150,233 person-years of follow-up (0.59/1000 person-years).  Cirrhosis-related deaths or hospitalizations were more significantly common in obese (0.81/1000 person-years) and overweight persons (0.71/1000 person-years) compared to normal-weight persons (0.45/1000 person-years).  This association of elevated BMI with cirrhosis-related death or hospitalization was not found among the subgroup of persons who consumed >0.3 alcoholic drinks/day.  These data show that obesity is a risk factor for cirrhosis-related death or hospitalization in persons who consume little or no alcohol.  (Abstract 9)

 

Subclinical hepatic encephalopathy (SHE) impairs fitness to drive.  Horst Koch et al. analyzed the driving performance of 48 cirrhotic patients (14 with SHE) and 49 clinical controls over a 22 mile course that included typical aspects of road traffic.  The rating results (including required instructor interventions to avoid an accident) of cirrhotic patients with SHE were significantly worse than those for cirrhotic patients without SHE or controls.  These findings demonstrate that the fitness to drive an automobile is impaired in patients with cirrhosis and SHE.  The authors concluded that all cirrhotic patients should be tested for SHE. (Abstract 522)

 

LIVER TRANSPLANTATION (LT)

Incidence of post-LT diabetes mellitus (DM).  Hugo Bonatti and associates assessed the incidence of post-LT DM in 402 patients who underwent 467 LTs at their center.  The incidence of post-LT DM was 39%, including the development of new-onset DM in 16% of patients.  The incidence of post-LT DM and new-onset DM in morbidly obese (MO) (BMI >35) recipients (n = 60) was 70% and 23.3%, respectively.  The estimated odds ratio for new onset DM in MO recipients was 2.4 (95% CI: 1.5-3.9).  In addition, recipients of a graft from a MO donor (n = 48) had an incidence of 56.3% for post-LT DM and 31.3% for new onset DM.  The estimate odds ratio for new onset DM in recipients who received a graft from a MO donor was 4.1 (95% CI: 1.9-9.0).  These data indicate that MO recipients are at an increased risk for post-LT DM.  Additional results from subgroup analysis, which require further study and confirmation, indicate that recipients of grafts from MO donors also are at an increased risk for post-LT DM. (Abstract 14)

 

Histologic abnormalities in live donor grafts.  Tram Tran and coworkers performed percutaneous liver biopsies on 56 donor candidates for living donor liver transplantation (LDLT) to evaluate liver histology. The mean age was 43 years and the average BMI was 25 kg/m2.  Mean biochemical tests were within normal reference ranges and no candidate reported significant alcohol consumption.  However, only 27% of donor candidates had normal liver biopsies.  The most common histological abnormality was steatosis (30%).  The clinical significance of these histological findings are unknown, but these results emphasize the need for extra care in the selection of liver donors and possibly the use of routine liver biopsy of potential LDLT donors.  (Abstract 17)

 

PEGINTERFERON (PEG-IFN) AND RIBAVIRIN (RBV) THERAPY FOR CHRONIC HEPATITIS C

Associated cytopenias.  A previous study reported that neutropenia commonly occurs in patients treated with PEG-IFN plus RBV.  Furqaan Ahmed et al. reviewed infectious-related serious adverse event (SAE) data from 4,243 patients treated with PEG-IFN plus RBV in the WIN-R Trial to determine the clinical relevance of the combination therapy-induced neutropenia.  Only 30 patients (0.7%) developed infectious SAEs while on PEG-IFN/RBV combination therapy.  One of these patients died (pneumonia); 27 patients were hospitalized; 24 patients were treated with antibiotics; and 7 patients required surgical intervention.  However, neither the mean ANC (absolute neutrophil count) nadir (p = 0.48) or the proportion of patients who developed an ANC <750/ul (20% in both groups) was different for patients who did or did not have infectious SAEs.  These findings showed that infectious SAEs occurred rarely in PEG-IFN/RBV-treated patients.  The clinical significance of PEG-IFN/RBV-induced neutropenia and the criteria for dose reduction or use of G-CSF remain unclear.  Combination PEG-IFN/RBV therapy has also been shown to induce anemia in chronic HCV patients.  Nezam Afduhal et al. conducted a double-blind placebo-controlled study and demonstrated that HCV patients treated with epoetin alfa while on PEG-IFN/RBV treatment had improved blood hemoglobin levels.  Thus, a greater proportion of patients receiving epoetin alfa, compared to those treated with placebo, maintained RBV therapy without dose reduction.  This study indicates that epoetin alfa treatments maintain RBV dose and improve anemia. (Abstracts 213 and 505)

 

NONALCOHOLIC FATTY LIVER DISEASE/NONALCOHOLIC STEATOHEPATITIS (NAFLD/NASH)

NAFLD in children.  Ariel Feldstein and others report the clinical course of 57 children with NAFLD who have been followed for up to 16 years at the Mayo Clinic in Rochester.  Among 20 patients who had a liver biopsy, necroinflammation, steatosis, fibrosis, and cirrhosis were present in 19 (95%), 15 (75%), 12 (60%), and 1 (5%) of patients, respectively.  At presentation, 43 (75%) patients were symptomatic with abdominal pain (53%), fatigue (26%), hepatomegaly (26%), and acanthosis nigricans (9%).  On follow-up 50% remained symptomatic and 75% continued to have abnormal liver function tests.  Follow-up liver biopsies in 3 children demonstrated progression of fibrosis.  This study shows that children with NAFLD can have a progressive course.  (Abstract 218)

 

Ethnic/racial differences in the prevalence of NASH.  Kristel Hunt and coworkers reviewed data from the Third National Health and Nutrition Examination Survey (NHANES III) (N = 7,933) to determine the prevalence of NASH in adults in the US.  Subjects with positive serologies for hepatitis B or C, transferrin saturation >45%, a history of drinking alcohol for >10 days/month, or a history of >4 drinks/episode were excluded.  Individuals with presumed NASH were defined as having an ALT level >38 U/L for men or >32 U/L for women with either a C-peptide >2.5 mg/mL, a Hgb A1C >6.2, or a BMI >25.  Presumed NASH was found in 4.9% of subjects, and 28% of the presumed NASH population was Hispanic.  In a second study, Jeff Browning and colleagues identified 41 patients with cryptogenic cirrhosis or cirrhosis due to NASH from the clinical records of Parkland Memorial Hospital between 1990 and 2001.  Sixty-eight percent of these patients had features of NASH (BMI >30 or adult onset diabetes mellitus).  Twenty-eight patients (68%) were Hispanic, and only 3 (7%) were African-American even though African-Americans made up >40% and Hispanics <26% of the patient population at Parkland.  During the last 5 years of study, the average yearly incidence of cryptogenic cirrhosis for Hispanics, whites, and African-Americans were 119.6, 23.5, and 8.4 per 100,000, respectively.  These data suggest that NASH and cirrhosis due to NASH have different prevalence rates among ethnic/racial groups.  (Abstracts 221 and 241)

 

UDCA treatment of NASH.  Keith Lindor and colleagues from the UDCA/NASH Study Group conducted a trial in which 168 patients with NASH were randomized to receive UDCA (13-15 mg/kg/day) or placebo.  Changes in serum liver biochemistries were not different between the 2 treatment groups.  In 95 evaluable patients, no differences in liver histology were found between the 2 treatment groups at 2 years of follow-up.  This study demonstrates that UDCA is not effective therapy for NASH.  (Abstract 336)

 

HEPATITIS C VIRUS INFECTION (HCV )

Vertical transmission.  Simone Ferrero and associates identified 182 women to be anti-HCV positive during pregnancy from 1990 to 2000 at their institution in Genoa, Italy.  The evaluable population comprised 170 mothers and 188 babies.  The vertical HCV transmission rate was 2.7%.  All of the HCV-infected infants were delivered from mothers who had viremia at delivery.  Mothers who transmitted HCV infection had higher levels of viremia, and the transmission rate was greater in mothers co-infected with HIV (5.4%; 2/37) than in HIV-negative mothers (2.0%; 3/151).  Birth weights, percentages of caesarean sections, premature deliveries, and obstetric complications were similar in a matched HCV-negative control group.  These data indicate that vertical HCV transmission is limited to viremic mothers, and high viral load and HIV-positivity predictive factors for transmission.  (Abstract 230)

 

Influence of steatosis on early virologic response (EVR).  Heather Patton et al. analyzed data from 160 HCV patients treated at a single center with IFN or PEG-IFN plus ribavirin.  EVR (a fall in HCV RNA levels by at least 2 log10 units by 12 weeks of treatment) was achieved by 115 (72%) patients.  Patients with genotype (GT) non-1 infection had a 7-fold greater EVR rate than patients with GT-1 infection.  Among patients with GT-1 infection (but not in GT non-1 infection), a greater percentage of patients with grade 0 steatosis, compared to patients with grade 1-3 steatosis, had an EVR (71% vs. 42%).  Stepwise analysis selected age, genotype, and steatosis grade as predictive factors for EVR. These results suggest that steatosis may influence treatment outcome for HCV GT-1-infected patients.  (Abstract 232)

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