Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis

Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 HCV-derived epitopes was determined by an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8(+) T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4(+) Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.     

Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV–HIV Co-infected Adults

Digestive Diseases and Sciences - There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. To evaluate the diagnostic performance...     

Elevated soluble CD30 characterizes patients with hepatitis C virus-induced liver allograft cirrhosis

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) significantly accelerates progression to allograft cirrhosis. Current biochemical parameters to monitor progression of chronic HCV after OLT have yielded low specificity and sensitivity. Here we investigated the HCV-specific immunity and serum levels of soluble CD30 (sCD30), a novel marker of Th2 immunity, in patients with and without allograft cirrhosis. Patients with hepatic inflammation but no cirrhosis (HIN, n=20) revealed elevated serum interferon (IFN)-gamma and high frequency of IFN-gamma producing CD4 T(h1) cells compared to those with hepatic cirrhosis (HFC, n=20) that had high interleukin (IL)-5 and IL-5 producing CD4 T(h2) cells. Patients with HFC, but not HIN, were found to have significantly higher levels of sCD30. Therefore, we conclude that lack of optimal Th1-type CD4 T cells is associated with HCV-induced allograft cirrhosis. Further, sCD30 may represent a novel marker for surveillance of hepatic cirrhosis in transplant recipients with chronic HCV infection.     

The Impact of Ethnicity on Hepatitis C Virus Treatment Decisions and Outcomes

Hepatitis C virus infection is a major public health concern. Approximately 4 million people are reported to be infected with the virus in the United States, and the annual death rate due to HCV-associated decompensated liver failure or hepatocellular carcinoma is estimated to be approximately 18,000 within the next decade. Therapeutic success, as measured by a sustained virologic response, is approximately 50 % in G1 patients with pegylated-interferon/ribavirin-based therapies. Independent studies have reported significant variation in response rates depending on the ethnicity or race of the patient, though the underlying reasons are not well understood. Historically, ethnic populations have been underrepresented in most large clinical trials of HCV therapies, even though these populations have disproportionately high rates of HCV infection. Recent clinical trials have investigated genetic variations in key biological pathways that may underlie the mechanisms responsible for the different rates of HCV clearance and treatment outcomes in ethnic populations treated with pegylated-interferon/ribavirin. However, as novel direct-acting antiviral drugs are added to, and eventually replace, existing treatment regimens, the role of the innate immune response in determining treatment outcomes will diminish. Socioeconomic and biological factors can impact rates of HCV infection, disease progression, and treatment outcomes in minority populations. Improved access to health care, novel antiviral treatments, and a better understanding of the host factors that contribute to disparities in treatment outcomes are expected to result in optimized treatment paradigms that directly target the virus, leading to improved outcomes for all patients.     

Primary biliary cirrhosis

Primary biliary cirrhosis is a chronic liver disease of unknown etiology characterized by slowly progressive intrahepatic cholestasis due to an inflammatory destruction of small intrahepatic bile ducts. The clinical course of PBC is variable ranging from a few years in rapidly progressive cases to a normal life-expectancy in a proportion of asymptomatic cases. The typical patient is a middle-aged woman who may present with pruritus, increasing pigmentation of the skin, and eventually jaundice. The level of serum alkaline phosphatase is almost invariably elevated, serum mitochondrial antibodies are present in more than 90 per cent, and an elevated serum IgM is usually present. PBC is associated with many immunologic abnormalities and appears to be a classic autoimmune disease. Some of the immune defects may be epiphenomena; others such as a marked defect in suppressor T cell function seem to be related to the pathogenesis of the disease. All drug therapy that is aimed at slowing the disease process is experimental. A place for immunosuppressive drugs in the management of PBC would be anticipated. However, no drug has to date been definitively shown to have a beneficial effect on the disease. Currently, the main treatments used are aimed at preventing or correcting the complications of intractable cholestasis. Patients with PBC and evidence of hepatic decompensation and/or poor quality of life make good candidates for liver transplantation. The current aim of therapy is to find an effective regime of immunosuppression that will make hepatic transplantation redundant for this disease.     

Disseminated histoplasmosis in a liver transplant recipient.

A 61-yr-old liver transplant recipient presented with abdominal cramping and nonbloody diarrhea resulting in orthostasis. Multiple ulcerations throughout the colon were seen during endoscopy, and biopsies from the ulcer edges revealed histoplasmosis. Treatment with a course of itraconazole improved the diarrhea. The patient later presented with pericarditis and symptomatic pleural effusions, the latter of which was confirmed to be a result of disseminated histoplasmosis. Treatment with amphotericin B led to resolution. Histoplasmosis should be considered in liver transplant patients with diarrhea and large ulcers in the colon. The presence of disseminated histoplasmosis should be ruled out once colonic histoplasmosis has been diagnosed.     

Conditions associated with hepatocellular carcinoma

The most important condition associated with hepatocellular carcinoma is chronic hepatitis B virus infection. This article summarizes the information linking hepatocellular carcinoma with conditions other than hepatitis B virus infection.