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In the United States, it is estimated that more than 4 million people are infected with the hepatitis C virus (HCV) and over 1.25 million are infected with HIV. With common routes of transmission, approximately 30% of HIV-infected individuals are coinfected with HCV. Deaths due to opportunistic infections from HIV declined with the advent of highly active antiretroviral therapy, whereas manifestations of end-stage liver disease have become more apparent with the increased longevity. Current efforts are directed toward understanding whether HIV/HCV coinfection affects the natural history of each virus. Early outcomes in treating coinfected patients for their HCV were below expectations, whereas recent treatment trials with highly selected patients and newer therapeutic agents have shown greater success. The aim of this paper is to review the epidemiology, natural history, and treatment outcomes, as well as unique challenges in the management of HIV/HCVcoinfected patients.

Albumin dialysis using the Molecular Adsorbents Recirculating System (MARS) has been found to be beneficial in the treatment of cirrhotic patients with acute decompensation to improve survival as well as reduce associated complications. The present study attempts to analyze the costs involved, and compare it to the benefit as a result of the MARS therapy, thus evaluating its cost-effectiveness. Using the results of a study by Kim et al. describing the effects of complications on the cost of hospitalization in alcoholic liver disease patients, the expenditure incurred in a group of 11 patients treated with standard medical therapy (five survivors) and a group of 12 patients treated with MARS in addition (11 survivors) (Heemann et al., Hepatology 2002) were analyzed. MARS resulted in a reduction of in-hospital deaths, as well as liver disease-related complications. Both these factors led to a substantial reduction of costs in the MARS group, which was enough to counterbalance the extra costs associated with extra-corporeal therapy. In the control group, the total hospitalization cost per survivor were calculated to be at $35,904. In the MARS group, the overall expenditure per survivor including standard medical therapy plus additional MARS liver support therapy were $32,036--a saving of nearly $4000 compared to the control group. Therefore, it appears that the benefits of MARS therapy are enough to justify the cost of treatment and safe hospital costs, at least in the described population. However, further studies are needed to confirm these results.

In patients with chronic hepatitis C virus (HCV) infection, liver fibrosis stage is a prognostic factor for therapy outcome. So far, a liver biopsy is necessary to determine disease stage accurately. We sought to develop a simple, noninvasive method of accurately predicting the degree of liver fibrosis in chronic HCV infection.We retrospectively studied 211 consecutive patients with chronic HCV, who received a liver biopsy at the Liver Center of the University of California, San Diego. A total of 58 of these patients had a positive history of alcohol abuse, and we analyzed them separately in a sensitivity analysis. AST/ALT ratio and platelet counts were determined in all patients. Fibrosis was staged using the METAVIR score.Both AST/ALT ratio and platelet counts correlated significantly with the disease stage (r = 0.190, p = 0.006, and r = -0.543, p0.00, respectively). In a sensitivity analysis, there was no correlation between AST/ALT ratio and disease stage for patients with a history of alcohol abuse. For patients without history of alcohol abuse, the correlation between disease stage, AST/ALT ratio, and platelet counts was r = 0.297, p0.00, and r = 0.560, p0.00, respectively. In these patients, AST/ALT ratioor =1 in combination with a platelet count of150,000/mm3 can identify patients with severe fibrosis or cirrhosis (stages 3 and 4) with a positive predictive value of 93.1%. Sensitivity, specificity, and negative predictive value were 41.2%, 99.1%, and 85.0%, respectively. In patients with ALT/AST ratio of1 or platelet counts of150,000/mm3, these laboratory parameters cannot predict liver fibrosis stage.AST/ALT ratio in combination with platelet counts may obviate a liver biopsy for fibrosis staging in some patients with chronic HCV infection.

It is important to assess the severity of hepatic encephalopathy (HE) and to quantitate improvement in HE after therapeutic interventions in a reliable and reproducible manner. The lack of a well standardized method of measurement has led to the use of different techniques by different clinical investigators, making a comparison between studies problematic. Although this issue had been noted more than 2 decades ago,1, 2 it is still unresolved and is reflected in the diversity of end-points and methods used in the assessment of acute HE in clinical trials over the last 15 years, e.g. West Haven criteria, Glasgow coma scale, PSE index with arterial or venous ammonia, and the EEG) (Table 1). Also different conditions have been classified as chronic HE (not reviewed here). The problem of how HE should be assessed, together with the considerable diversity of terms used to define different clinical settings, prompted a gathering of a panel of international experts to reach a consensus. Table 1. Clinical treatment trials of episodic hepatic encephalopathy (precipitated or spontaneous) in the last 15 years. SMT: standard medical treatment Author and Year Type of patients Therapy studied Primary End-point Measurement of HE Kramer, 200115 Stage II and III HE Cirrhosis Sorbent dialysis + SMT vs SMT only Sensory evoked potentials Clinical staging (West Haven), sensory evoked potentials automated EEG Laccetti, 200016 Stage III-IV HE Cirrhosis Flumazenil + SMT vs placebo + SMT Clin ical improvement Glasgow coma scale Barbaro, 199816 Stage IVa HE Cirrho sis Flumazenil + lactulose vs placebo + lactulose Clinical improvement and EEG. EEG and modified Glasgow coma scale (Pappas and Jones), including: verbal ability, eye-opening, pupillary light reflex, corneal reflex, spontaneous eye movements, oculocephalic reflex, motor response, respiration pattern Barbaro, 199818 Stage III-IVa HE Cirrhosis Flumazenil + lactulose vs placebo + lactulose Clinical improvement and EEG EEG and modified Glasgow coma scale (Pappas and Jones), including: verbal abilitiy, eye-opening, pupillary light reflex, corneal reflex, spontaneous eye movements, oculocephalic reflex, motor response, respiration pattern Gyr, 199614 Stage I-III HE Cirrhosis Flumazenil vs placebo (Lactulose permitted in both groups) Clinical improvement Own adapted clinical PSE score, EEG Van der Rijt, 199519 HE staged by EEG (clinical stage varied from 0 to IV) Acute or chronic liver disease Flumazenil vs placebo Clinical improvement and EEG Clinical staging asses sed by own classi ficatio n: stage I: > 2 of inverted sleep pattern, disturbed memory, impaired serial 7’s, slowness of speech, flapping tremor; stage II: > 2 of lethargy, time disorientation, asterixi s; stage III: > 2 of state that subject had to be stimulated repetitively to open eyes or execute commands, place and person disorientation; stage IV: coma. EEG Cadranel, 199520 Stage II-IV HE Cirrhosis Flumazenil vs placebo Clinical improvement and EEG Clinical grading with own classification: I: euphoria/depression, mild confusion, slowness, disordered sleep rhythm; II: drowsiness, inappropriate behaviour, accentuation of grade I; III: stupor, patient sleeps most of time but rousable, incoherent speech, marked confu sion; IVa: coma, coordinated response to pain; IVb: hyperextension and pronosupination to pain stimuli; IVc: no response to pain; V: clinica l decerebration. EEG Pomier-Layrargues, 199421 Stage IV HE Cirrhosis Flumazenil + lactulose vs placebo + lactulose Clinical improvement Modified Glasgow coma score, including: verbal ability, eyeopening, pupillary light, corneal and oculocephalic reflexes, spontaneous eye movements, motor response, respiration pattern. EEG Blanc, 199422 Acute HE Cirrhosis Lactulose + neomycin vs placebo PSE index PSE Index (mental state (West Haven), number conection test, EEG, asterixis and arterial ammonia) Strauss, 199223 Acute HE stages I-IV Cirrhosis Neomycin vs placebo Clinical improvement Clinical criteria (I to IV) but no reference or explanation. Sushma, 199224 Acute HE stages II-IV Cirrhosis Lactulose vs sodium benzoate Clinical improvement Mental state (WH), asterixis, psychometric tests, arterial ammonia, EEG, evoked potentials Vilstrup, 199025 Acute HE stages II-IV Cirrhosis BCAA iv + lactulose vs glucose iv + lactulose Clinical improvement Glasgow coma scale Klotz, 198926 Stage III HE Cirrhosis Flumazenil vs placebo Clinical improvement Coma status evaluated by reactions and reflexes to stimuli (no further explanation or reference) Uribe, 198727 Acute HE (stage II Cirrhosis Lactitol and lactose enemas vs nonacidifying enemas PSE index PSE index: mental state (WH), NCT, asterixis, EEG, fasting arterial ammonia. Morgan, 198713 Acute HE Cirrhosis Lactitol vs lactulose PSE index PSE index: mental state (WH), NCT-A, asterixis, EEG, venous ammonia