Henry C. Bodenheimer

A Randomized Trial of a Hepatitis Care Coordination Model in Methadone Maintenance Treatment

OBJECTIVESnWe evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients.nnnMETHODSnWe conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services.nnnRESULTSnCompared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV-HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61).nnnCONCLUSIONSnHepatitis care coordination was efficacious in increasing adherence to HAV-HBV vaccination and HCV clinical evaluation among methadone patients.

Accelerated hepatitis C virus kinetics but similar survival rates in recipients of liver grafts from living versus deceased donors

This study tested the hypothesis that hepatitis C virus (HCV) RNA and core antigen levels rise more rapidly after liver transplantation (LT) in recipients of grafts from living donors (LD) versus deceased donors (DD). Eleven consecutive LD and 15 DD recipients were followed prospectively. Before LT, median HCV RNA levels were similar: 5.42 (LDLT) and 5.07 (DDLT) log10 IU/mL (P = NS). During the first 7 hours after LT a trend toward a greater HCV RNA decrease in LDLT patients was seen, although they received fewer blood replacement products during surgery. HCV RNA levels rose more rapidly in LDLT patients between days 1 and 3 (P = .0059) and were higher in this group on days 2, 3, 4, and 5. Core antigen levels were significantly higher in LDLT patients on days 3 and 5, although they were similar before LT (P = NS). Alanine aminotransferase (ALT) values were higher among LDLT patients from 8 to 14 days and from 4 to 24 months. Two‐year graft and patient survival were 73% for LDLT patients and 80% for DDLT patients (P = NS). In conclusion, viral load rose more rapidly in LD recipients and reached higher levels shortly after surgery. Greater ALT elevations were evident in the LDLT group, but survival rates were similar. The trend toward a greater initial viral load decrease in patients with LD grafts and the significantly sharper increase suggest that the liver plays a predominant role in both HCV clearance and replication. (HEPATOLOGY 2005;42:1420–1428.)

Evaluation of fatigue in U.S. patients with primary biliary cirrhosis

OBJECTIVES:Fatigue, which may have a significant impact on quality of life, is the most common reported symptom in primary biliary cirrhosis (PBC). Multiple instruments to quantify fatigue and quality of life in liver disease have been validated, but have not been broadly applied to U.S. PBC patients. This study examines the extent of fatigue and its effect on quality of life in U.S. PBC patients.METHODS:Seventy patients with PBC were administered two validated questionnaires about quality of life (the Mayo version of the NIDDK-QA) and fatigue (the Fisk Fatigue Impact Score) and a proposed physical measure of fatigue in PBC (the grip strength test) on the day of routine physician visit. Nonparametric methods were employed.RESULTS:The fatigue and quality of life domain scores (physical functioning, liver symptoms, health satisfaction, Karnofsky index) discriminated between patients with and without self-reported fatigue (p < 0.05), as opposed to the grip strength results. Fatigue and quality of life domains correlated strongly with each other (r between 0.33 and 0.74, p ≤ 0.006) and not with the grip strength results. Neither quality of life nor fatigue scores correlated with age.CONCLUSIONS:The correlation between fatigue and quality of life scores suggests fatigue has an impact on quality of life in U.S. primary biliary cirrhosis patients. However, our fatigue scores suggest U.S. PBC patients have less fatigue than non-U.S. PBC patients. The grip strength is an insensitive measure of fatigue in U.S. PBC patients.

Hepatic expression of toll-like receptors 3, 4, and 9 in primary biliary cirrhosis and chronic hepatitis C

UNLABELLEDnToll-like receptors (TLRs) may play a role in the inflammatory patterns observed in primary biliary cirrhosis (PBC) and chronic hepatitis C (CHC). We investigated TLR 3, 4 and 9 expression in PBC and CHC using immunohistochemical staining.nnnMETHODSnPatient biopsies of PBC (N=11) and CHC (N=15) were compared to disease free livers (n=7). The extent of TLR staining was assessed separately according to a semi-quantitative scale for hepatocytes, cholangiocytes and portal mononuclear cells (PMC).nnnRESULTSnIn hepatocytes, TLR4 expression was increased (PBC; P=0.019), as was TLR9 (PBC; P=0.006, CHC; P=0.001). Cholangiocyte expression of TLRs 4 and 3 was reduced in both PBC (TLR4; P<0.0001, TLR3; P=0.006) and CHC (TLR4; P<0.0001, TLR3; P=0.014). Cholangiocyte expression of TLR9 was elevated for both groups and was significant in CHC (P=0.0115). PMCs showed up-regulation of TLR9 in PBC (P=0.022) and CHC (P=0.0001), with almost no expression of TLR 3 or 4.nnnCONCLUSIONSnIn PBC and CHC, hepatocytes showed increased TLR 4 and 9 expression without change in TLR3. Cholangiocytes showed increased TLR9 expression as opposed to down-regulation of TLRs 3 and 4. PMCs in both diseases had significantly increased TLR 9 expression perhaps implicating TLR9 expression in chronic liver inflammation.

Efficacy of high-dose interferon in combination with ribavirin in patients with chronic hepatitis C resistant to interferon alone.

OBJECTIVE:Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its utility in patients who have not responded to prior interferon therapy is not clear. Furthermore, the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial.METHODS:We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon α-2b and ribavirin (1000–1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period.RESULTS:The mean age of the subjects was 47 yr (range 28–68 yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21(14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon α-2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virological response to the 12-month course of treatment. Overall, 11 of 81 patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy. The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance (p = 0.09). However, among the nonresponder patients alone, there was an increased sustained response in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the 5-MU groups (p = 0.17).Conclusions:Sustained virological response to combined interferon α-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treated patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the prior nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable.

Chronic Hepatitis C Virus and Celiac Disease, is there an Association?

Celiac disease (CD) has been epidemiologically associated with chronic hepatitis C (HCV), and CD activation after the initiation of interferon (IFN-α) in patients with HCV is documented. However, clear association of CD and HCV is lacking. A prospectively maintained database of 878 CD patients showed a prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and depression prompted the diagnosis of CD during or after IFN-α therapy in four cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls and 19 disease controls) were prospectively screened for CD. The mean age of the subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received IFN-α therapy (16% at the time of testing for CD). Two HCV patients (1%) had positive tTG-IgA but these had negative endomysial antibody (EMA) and normal duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine screening of CD in HCV patients is not warranted, however, the presence of CD should be considered in the setting of clinical deterioration during or after IFN-α therapy.

Atorvastatin Does Not Improve Liver Biochemistries or Mayo Risk Score in Primary Biliary Cirrhosis

Statin treatment reduces hypercholesterolemia and may be anti-inflammatory. Case reports noted decreased alkaline phosphatase and histological improvement following statin treatment in primary biliary cirrhosis. The objective of this study was to assess the long-term effects of statin treatment in primary biliary cirrhosis. A retrospective analysis compared clinical and biochemical data from 15 hypercholesterolemic individuals with primary biliary cirrhosis who were treated long-term with atorvastatin with an age and gender matched, primary biliary cirrhosis control group. A significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol (pxa0≤xa00.002) was observed throughout atorvastatin treatment (median time 2.5xa0years). LDL-cholesterol levels in the control group were not significantly changed after 2xa0years (pxa0>xa00.050). No significant changes were noted in alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and Mayo Risk Score in either group (pxa0>xa00.05). Long-term atorvastatin treatment reduced LDL-cholesterol in primary biliary cirrhosis, but there was no evidence of any anti-inflammatory effect.

Serrated Adenoma is a Risk Factor for Subsequent Adenomatous Polyps

Background Serrated adenomas (SA) are histologically defined by the presence of both hyperplastic and adenomatous features. These uncommon polyps are thought to play an important role in the development of sporadic colorectal cancers (CRC) with microsatellite instability (MSI). There is paucity of data on the risk of progression of SA to CRC. This study was undertaken to define the relationship between SA and the future development of adenomatous polyps. Methods Colonoscopic biopsies that contained a pathologic diagnosis of SA were identified from a pathology database of a major urban academic medical center. Those patients with absence of concomitant malignancy, complete colonoscopy, good or adequate prep and presence of at least one follow-up procedures were identified. These were matched to controls by age, sex, indication for colonoscopy, polyp type and number and duration of follow-up. Outcomes of the follow-up procedures were compared. Results Between January 1997 and June 2005 17,226 colonoscopic biopsies and polypectomies were performed. Of these, 80 patients (0.5%) with SA were found, and of these SA, 80% were found in the left colon. The average age of patients undergoing colonoscopy was 58.5 years, and the average age of patients with SA was 68 years (Pxa0=xa00.004). Of all patients with SA, 7 (9%) had concomitant CRC. The final groups contained 17 patients and 17 controls, respectively, and were well matched. The mean follow-up interval in the patient group was 29xa0months vs. 31xa0months in the control group (Pxa0=xa00.82). On follow-up examination four patients (24%) and no controls had adenomatous polyps (Pxa0=xa00.01). Conclusions While SA are uncommon, they are commonly associated with colorectal cancer. Serrated adenomas appear to be found more commonly in the left colon and in older patients. This study found a significant association between SA and the subsequent development of adenomatous polyps. Further studies are needed to define appropriate preventive strategies for these patients.

Trends in the indication and method of liver biopsy for hepatitis B and C.

Background and AimsLiver biopsy plays a crucial role in assessing inflammation and fibrosis in chronic hepatitis. The aim of this study was to compare the indications and methods for performing a liver biopsy over a 15-year period when there were evolving strategies and increasing therapeutic options for the treatment for chronic hepatitis B (HBV) and C (HCV).MethodsWe reviewed all percutaneous liver biopsies performed at our center from 1992 to 2007 using a pathology database. Variables collected included indication for biopsy, use of real-time ultrasound (US) guidance, and complications associated with the biopsy.ResultsA total of 3,572 total liver biopsies were performed between 1992 and 2007 with a gradual increase in annual liver biopsies from 1992 to 2001. After a peak in 2003, there was a gradual decline in liver biopsies performed. The number of liver biopsies done for HCV peaked in 2003, followed by an annual decrease until 2006, while the number of annual biopsies done for HBV increased during the same period. In addition, the proportion of liver biopsies performed with real-time US-guidance increased steadily since 1997.ConclusionsChanges in liver biopsy trends at our center may be related to several factors, including the evolving treatment strategies for HCV and HBV. Percutaneous liver biopsies were increasingly performed using real-time US-guidance over the past decade, a change that may reflect practice patterns around the country.