Rudra Rai

Progression of liver fibrosis among injection drug users with chronic hepatitis C

Although most hepatitis C virus (HCV) infections are acquired by injection drug use, prospective data on the progression of liver fibrosis are sparse. Baseline liver biopsies were obtained (1996–1998) on a random sample of 210 out of 1667 HCV‐positive injection drug users (IDUs). Subjects were followed biannually, with a second biopsy offered to those eligible. Paired biopsies were scored 0 to 6 (modified Ishak score), significant fibrosis was defined as score 3 or greater, and progression of fibrosis was defined as an increase 2 or more units or clinical evidence of end‐stage liver disease. Predictive values of blood markers [FibroSURE, aspartate aminotransferase‐to‐platelet‐ratio index (APRI) and alanine aminotransferase (ALT)] were assessed for detection of contemporaneous and future liver fibrosis. Among 119 prospectively followed IDUs, 96% were African American; 97% HCV genotype 1a/b; 27% HIV‐infected, and median age was 42 years. Most (90.7%) did not have significant liver fibrosis at first biopsy. Although predictive value for detecting insignificant fibrosis at first biopsy was greater than 95% for FibroSURE, APRI, and ALT, specificities were 88.9%, 72.7%, and 72.7%, respectively. After 4.2 years median follow‐up, 21% had progression of fibrosis, which was significantly associated with serum level of HCV RNA and ALT. No serological test had predictive value greater than 40% for contemporaneous or future significant fibrosis. Even initial biopsy result had only a 30.4% value for predicting future significant fibrosis. In conclusion, significant liver fibrosis and progression were detected in some, but not most, IDUs in this cohort. In this setting with low fibrosis prevalence, FibroSURE, ALT, and APRI tests predict insignificant fibrosis; however, further work is needed to find noninvasive markers of significant liver fibrosis. (HEPATOLOGY 2006;43:788–795.)

Review: regulation of liver regeneration by pro-inflammatory cytokines.

The liver has tremendous regenerative capacity. This distinguishes it from other vital organs (e.g. the brain, heart and lungs) that cannot replace functional tissue once it has been destroyed. Although hepatocytes rarely proliferate in the healthy adult liver, virtually all surviving hepatocytes replicate at least once after 70% partial hepatectomy. Therefore, partial liver resection has been used to characterize mechanisms that regulate liver regeneration. Residual hepatocytes up‐regulate both proliferative and liver‐specific gene expression in order to preserve tissue specific function. In addition, hepatocyte proliferation is tightly co‐ordinated to complement regenerative responses in hepatic nonparenchymal cells (e.g. endothelia, biliary epithelia, stellate and Kupffer cells), so that the entire organ can be reconstituted within days. Studies with neutralizing antibodies to tumour necrosis factor‐α (TNF) clearly demonstrate that, after partial hepatectomy, TNF promotes liver cell proliferation. The present review focuses on the regulation of the hepatocyte proliferative response by pro‐inflammatory cytokines.

Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors

Introduction. The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+) or hepatitis C virus seronegative (HCV−) donors into HCV+ recipients; and 2) to determine whether HCV+ patients with end‐stage renal disease (ESRD) might benefit from receiving renal allografts from HCV+ donors. 
Methods. From January 1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric renal transplants. The data were reviewed retrospectively. Nineteen of the renal transplants were performed with allografts obtained from 15 HCV+ donors and 10 with allografts obtained from 10 HCV− donors. The median follow‐up was 16.2 months, with an average of 15.4±2 months. 
Results. Recipients of HCV+ renal allografts had shorter waiting times for transplantation. On average, patients who received a kidney from HCV+ donors were transplanted 9±3 months after being placed on the transplant list, compared to 29±3 months for patients who received a kidney from a HCV− donor. Shorter waiting times were noted in every blood type group. There were no significant differences in rejection episodes, infectious complications, renal function, liver function, graft survival, or patient survival. 
Conclusions. The use of renal allografts from HCV+ donors for HCV+ recipients shortens the waiting time for these patients, with no short‐term differences in renal and liver function, graft loss, or patient survival.

Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines.

ABSTRACT Gadolinium chloride (GdCI3) is commonly used to deplete the liver of Kupffer cells (KC) and has been shown to decrease hepatic phagocytic activity and to abolish hepatic expression of certain KC-specific antigens. However, the exact fate of the KCs after GdCI3 treatment remains unclear. To determine if GdCI3 actually decreases the total number of KCs in the liver, we labeled phagocytically-active KC by administering fluorescent-labeled latex beads to rats treated with either normal saline or GdCI3. Total hepatic fluorescence and the distribution of fluorescence within liver acini were evaluated by intravital microscopy. Hepatic mRNA levels of KCR, a KC-specific gene product, and Pu-1, a ubiquitous monocyte gene product, were assessed by Northern blot analysis, and differences in the expression of pro-inflammatory (tumor necrosis factor (TNF)-±) and anti-inflammatory (interleukin (IL)-10) cytokines were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Our results indicate that GdCI3 does not significantly reduce the number of phagocytically active cells in the liver, but alters the acinar distribution of these cells and may provoke a switch in the KC phenotype such that these cells no longer express KCR or IL-10. GdCI3 pretreatment inhibited stress-related induction of IL-10, but failed to down-regulate expression of TNF-±. This phenotypic change is likely to have important consequences because it permits relative overexpression of TNF-±.

The utility of TIPS in the management of Budd-Chiari syndrome

Background and Aim:Budd-Chiari syndrome (BCS) is a rare condition associated with hepatic venous outflow obstruction classically treated with portosystemic shunts or liver transplantation. Recent reports indicate promising results with the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of these patients. Patients and Methods:We reviewed a 10-year single-institution experience with TIPS in patients diagnosed with BCS. Results:Eleven patients with BCS underwent TIPS procedures, 3 of whom carried a diagnosis of paroxysmal nocturnal hemoglobinuria, a relative contraindication for liver transplantation. One TIPS procedure was unsuccessful for technical reasons. No patient suffered mortality or major morbidity related to the TIPS procedure. The mean reduction of portal venous pressures was 43.7%, with a mean decrease of 73% in the pressure gradient. Of the 7 patients where long-term follow-up was available, 57% had shunts which remained patent but required several nonsurgical revisions for occlusion, with an average assisted patency of 37.5 months. Conclusions:TIPS is an effective modality in the treatment of patients with BCS, especially for those who are not candidates for liver transplantation. TIPS can be successfully used as a bridge to surgical portosystemic shunting, as well as liver transplantation, but may cause technical difficulties when performing transplantation.

Features of recurrent primary sclerosing cholangitis in two consecutive liver allografts after liver transplantation.

Recurrence of primary sclerosing cholangitis (PSC) after liver transplantation is very uncommon. The true incidence of recurrence is unknown, mainly because of the difficulty in differentiating ischemic strictures from that of recurrent disease. Primary sclerosing cholangitis and ischemic strictures have identical histopathologic and cholangiographic features. We report a young man who had recurrence of PSC in two allografts and report our experience in 32 patients who had liver transplantation for PSC. Six patients (18%) had evidence of non-anastomotic strictures and, of these, only one patient (reported here) had unequivocal evidence of true recurrence. The strictures in other five patients happened because of ischemia. The recurrence of the disease in two allografts in an immunosuppressed patient, in the absence of ischemia, chronic rejection, or any known pathogen, raises the question of the role of an unidentified infectious agent in the etiopathogenesis of PSC.

Biliary Tract Disease in Pregnancy

Abstract The timely diagnosis and treatment of biliary tract conditions during pregnancy are challenging. Familiarity with the anatomic and physiologic changes present in normal pregnancy is essential, as is the knowledge of relative risk of complications by trimester. Physicians should be aware that virtually all complications that occur in the management of these conditions are caused by delay in the detection of the disease process. Recent advances in minimally invasive therapy including laparoscopic surgery and therapeutic gastro-intestinal endoscopy have changed the traditional approach to biliary tract disease in pregnancy. We present a case report of a patient with acute gallstone pancreatitis during pregnancy managed endoscopically without the use of fluoroscopy.